StudyFinder
Search Results Within Category "Cancer"
Suggestions within category "Cancer"
Bladder
Brain
Breast
Cervical
Colorectal
Endometrial
Esophageal
Head and Neck
Kidney
Leukemia
Liver
Lung
Lymphoma
Melanoma
Multiple Myeloma
Other Blood Disorders
Other Gastrointestinal
Other Gynecologic Cancers
Ovarian
Pancreas
Pediatric
Prostate
Sarcoma
Testicular
Thyroid
Urothelial
34 Study Matches
APVO436 Phase 1b/2 Study in Patients With Newly Diagnosed AML
A multi-center, open-label, dose-finding study of five dose levels of APVO436 in combination with venetoclax and azacitidine (ven/aza) in adult patients with newly diagnosed, CD123+ AML.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
ALL
18 Years to old
PHASE1
NCT06634394
STU-2024-1192
Inclusion Criteria:
* 1. Age ≥18 years. 2. Patient must have confirmation of AML based on 2016 World Health Organization (WHO) criteria and not been previously treated.
• Patients must have CD123-positive AML as confirmed by local flow cytometry (or immunohistochemistry \[IHC\]). Confirmation at diagnosis is acceptable.
• Patient must be considered ineligible for induction therapy defined by at least one of the following:
• ≥75 years of age
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or 3
• Cardiac disorder (e.g., congestive heart failure requiring treatment, ejection fraction ≤ 50%, or chronic stable angina)
• Pulmonary disorder (e.g., DLCO ≤65% or FEV1 ≤65%)
• Creatinine clearance 30-45 mL/min based on Cockcroft-Gault or Modified of Diet in Renal Disease (MDRD) formular
• Hepatic disorder with total bilirubin between 1.5 and 3 times the ULN 5. Patient must have a projected life expectancy of ≥12 weeks
Exclusion Criteria:
• Patient has received treatment with the following:
• A hypomethylating agent, venetoclax, and/or chemotherapeutic agent for AML, myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), or myelodysplastic/myeloproliferative neoplasms (MPS/MPN)
• CAR-T cell therapy or history of allogeneic hematopoietic stem cell transplant (HSCT)
• Experimental therapies for MDS or AML
• Patient is currently participating in another interventional research study.
• Patient has history of MPN including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia (CML) with or without BCR-ABL1 translocation, or AML with BCR-ABL1 translocation.
• Patient has acute promyelocytic leukemia.
• Patient has a current autoimmune disorder requiring immunosuppressive therapy such as systemic (oral or IV) steroid therapy \>10 mg methylprednisolone daily or its equivalent
• Patient is receiving concurrent corticosteroid therapy as an anticancer drug (any dose).
• Patient has known active CNS involvement with AML. Patients who received intrathecal chemotherapy for prophylaxis of AML in the CNS prior to enrollment may enroll in this study.
• Creatinine clearance \<30ml/min based on Cockcroft-Gault or MDRD formular.
• Bilirubin of \>3xULN in the absence of Gilbert's Syndrome.
• AST and/or ALT \>3 times the ULN.
DRUG: APVO436, DRUG: Venetoclax, DRUG: Azacitidine
Acute Myeloid Leukemia (AML), Myeloid and Monocytic Leukemia
Acute Myeloid Leukemia
UT Southwestern
A Study to Evaluate the Risk of Tumor Lysis Syndrome (TLS) in Adult Participants Receiving Oral Venetoclax in Combination With Intravenously Infused Obinutuzumab or Oral Acalabrutinib for Previously Untreated Chronic Lymphocytic Leukemia (CLL)
Chronic lymphocytic leukemia (CLL) is the most common leukemia (cancer of blood cells). The purpose of this study is to assess the safety of venetoclax in combination with obinutuzumab or acalabrutinib in the treatment of CLL. Adverse events and change in disease activity will be assessed. Venetoclax in combination with obinutuzumab or acalabrutinib is being investigated in the treatment of CLL. Study doctors put the participants in 1 of 4 groups, called treatment arms. Participants will receive oral venetoclax in combination with intravenously (IV) infused obinutuzumab or oral acalabrutinib at in different dosing schemes as part of treatment. Approximately 120 adult participants with CLL who are being treated with venetoclax will be enrolled in the study in approximately 80 sites worldwide. Participants in Arm A will receive oral venetoclax in combination with IV infused obinutuzumab, with a 5 week venetoclax ramp up. Participants in Arm B will receive oral venetoclax in combination with oral acalabrutinib, with a 5 week venetoclax ramp up. Participants in Arm C and Arm D will receive oral venetoclax in combination with oral acalabrutinib, with differing venetoclax ramp up periods. The total study duration is approximately 28 months. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Farrukh Awan
ALL
18 Years to old
PHASE3
NCT06428019
STU-2024-0660
Inclusion Criteria:
* Diagnosis of documented, previously untreated, chronic lymphocytic leukemia (CLL) requiring treatment according to the 2018 international workshop on chronic lymphocytic leukemia (iwCLL) criteria and have a life expectancy of \> 6 months.
* Previously untreated small lymphocytic lymphoma (SLL) meeting the 2018 iwCLL criteria for treatment will also be equally considered as CLL for eligibility, screening, treatment and evaluation.
* Eastern Cooperative Oncology Group (ECOG) performance status \<= 2.
* Adequate marrow function independent of growth factor or transfusion support within 2 weeks of screening, unless cytopenia is due to marrow involvement of CLL as listed in the protocol.
* Creatinine clearance (CrCl) \>= 30 mL/min using the Cockcroft-Gault formula are eligible for inclusion.
Exclusion Criteria:
• Active/uncontrolled infection, no Richter's transformation, no active immune thrombocytopenia.
DRUG: Venetoclax, DRUG: Acalabrutinib, DRUG: Obinutuzumab
Chronic Lymphocytic Leukemia, Lymphoid Leukemia
Chronic Lymphocytic Leukemia, CLL, Venetoclax, ABT-199, Obinutuzumab, Acalabrutinib
UT Southwestern
Study of Revumenib, Azacitidine, and Venetoclax in Pediatric and Young Adult Patients With Refractory or Relapsed Acute Myeloid Leukemia
This is a research study to find out if adding a new study drug called revumenib to commonly used chemotherapy drugs is safe and if they have beneficial effects in treating patients with acute myeloid leukemia (AML) or acute leukemia of ambiguous lineage (ALAL) that did not go into remission after treatment (refractory) or has come back after treatment (relapsed), and to determine the total dose of the 3-drug combination of revumenib, azacitidine and venetoclax that can be given safely in participants also taking an anti-fungal drug. Primary Objective * To determine the safety and tolerability of revumenib + azacitidine + venetoclax in pediatric patients with relapsed or refractory AML or ALAL. Secondary Objectives * Describe the rates of complete remission (CR), complete remission with incomplete count recovery (CRi), and overall survival for patients treated with revumenib + azacitidine + venetoclax at the recommended phase 2 dose (RP2D).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kathleen Ludwig
ALL
1 Year to 30 Years old
PHASE1
NCT06177067
STU-2024-0647
Inclusion Criteria:
Participants must have a diagnosis of AML or ALAL and meet the criteria below:
* Refractory leukemia, defined as persistent leukemia after at least two courses of induction chemotherapy, or relapsed leukemia, defined as the re-appearance of leukemia after the achievement of remission. Patients must have ≥5% blasts in the bone marrow as assessed by morphology or ≥1% blasts flow cytometry. However, if an adequate bone marrow sample cannot be obtained (e.g., in a patient with acute megakaryoblastic leukemia with marrow fibrosis), patients may be enrolled if there is unequivocal evidence of leukemia with ≥5% blasts by morphology or ≥1% blasts flow cytometry in the blood.
* Presence of KMT2A rearrangement (KMT2Ar), NUP98 rearrangement (NUP98r), NPM1 mutation or fusion, PICALM::MLLT10, DEK::NUP214, UBTF-TD, KAT6A::CREBBP, or SET::NUP214
* Adequate organ function, defined as total bilirubin \< 1.5 × institutional upper limit of normal for age or normal conjugated bilirubin (for patients with known Gilbert's syndrome, total bilirubin \<3 × the ULN) unless attributed to leukemia, calculated creatinine clearance ≥60 mL/min/1.73 m\^2, and left ventricular ejection fraction ≥ 40%
* QTcF \< 480 msec (average of triplicate)
* Age ≥ 1 year and ≤ 30 years. The upper age limit may be defined by each institution, but may not exceed 30 years.
* Lansky ≥ 60 for patients who are \< 16 years old and Karnofsky ≥ 60% for patients who are \> 16 years old.
* At least 14 days or 5 half-lives (whichever is longer) must have elapsed since the completion of myelosuppressive therapy, with the exception of low-dose therapy used for cytoreduction according to institutional standards, such as hydroxyurea or low-dose cytarabine (up to 200 mg/m\^2/day). In addition, all toxicities must have resolved to grade 1 or less.
* Patients must have a leukocyte count \<25,000 cells/uL. Low-dose therapy, such as hydroxyurea or cytarabine as described above, to achieve this limit is acceptable.
* For patients who have received prior HCT, there can be no evidence of GVHD and greater than 60 days must have elapsed since the HCT, and patients should be off calcineurin inhibitors for at least 28 days prior to the start of protocol therapy. Physiologic prednisone for the treatment of adrenal insufficiency is acceptable..
* Patients must be taking posaconazole or voriconazole, which must be started at least 24 hours prior to the start of therapy.
* Patients of reproductive potential must agree to use effective contraception for the duration of study participation.
* Patients must be able to swallow tablets.
Patients who meet the criteria listed above are eligible for enrollment and treatment on the trial. However, patients in first relapse who are suitable for and willing to receive intensive remission induction therapy should be offered such therapy if deemed appropriate by the treating physician.
Exclusion Criteria:
* Patients who are pregnant or breastfeeding are not eligible.
* Patients with Down syndrome, acute promyelocytic leukemia, juvenile myelomonocytic leukemia, or bone marrow failure syndromes are not eligible.
* Patients with uncontrolled infection are not eligible. Patients with infections that are controlled on concurrent anti-microbial agents are eligible. DRUG: Revumenib, DRUG: Venetoclax, DRUG: Azacitidine, DRUG: intrathecal (IT) chemotherapy, DRUG: Cytarabine, DRUG: Methotrexate
Refractory Acute Myeloid Leukemia, Relapsed Acute Myeloid Leukemia, Acute Leukemia of Ambiguous Lineage, Myeloid and Monocytic Leukemia
Children’s Health
A Dose Escalation and Dose Expansion Study of Intratumoral ONM-501 Alone and in Combination With Cemiplimab in Patients With Advanced Solid Tumors and Lymphomas. (ON-5001)
A phase 1, multicenter, open label, non-randomized dose escalation and dose expansion study to examine the maximum tolerated dose, (MTD), minimum effective dose (MED) and/or recommended dose for expansion (RDE) of intratumoral ONM-501 as monotherapy and in combination with a PD-1 checkpoint inhibitor in patients with advanced solid tumors and lymphomas.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Heather McArthur
ALL
18 Years and over
PHASE1
NCT06022029
STU-2023-0921
Inclusion Criteria:
• Ability to understand and willingness to sign written informed consent before performance of any study procedures
• Age ≥ 18 years
• Participants with solid tumors or lymphomas, confirmed by available histopathology records or current biopsy, that are advanced, nonresectable, or recurrent and progressing since last antitumor therapy, and for which no alternative standard therapy exists.
• Participants must have a minimum of one injectable and measurable lesion.
• Participants with prior Hepatitis B or C are eligible if they have adequate liver function
• Participants with human immunodeficiency virus (HIV) are eligible if on established HAART for a minimum of 4 weeks prior to enrollment, have an HIV viral load \<400 copies/mL, and have CD4+ T-cell (CD4+) counts ≥ 350 cells/uL
• Adequate bone marrow function:
• Adequate liver function
Exclusion Criteria:
Patients will be excluded from this study if they meet any of the following criteria (Part 1a and Part 1b).
• Other malignancy active within the previous 2 years except for basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast that has completed curative therapy.
• Major surgery within 4 weeks before the first dose of study drug.
• Brain metastases that are untreated or in the posterior fossa or involve the meninges. Participants with stable or previously treated progressing brain metastases (except in the posterior fossa or involving the meninges) may be permitted in a case-by-case basis at the Sponsor's discretion.
• Prolongation of corrected QT (QTc) interval to \>470 millisecond (ms) for males and females when electrolytes balance is normal.
• Females who are breastfeeding or pregnant at screening or baseline
• Females of childbearing potential that refuse to use a highly effective method of contraception.
• Has uncontrolled or poorly controlled hypertension as defined by a sustained BP \> 9. Has received prior investigational therapy within 5 half-lives of the agent or 4 weeks before the first administration of study drug, whichever is shorter.
• Has had any major cardiovascular event within 6 months prior to study drug 10. Has known hypersensitivity to any component in the formulation of ONM-501
• Has an active infection requiring systemic treatment
• Is participating in another therapeutic clinical trial Additional Exclusion Criteria for ONM-501 in Combination with cemiplimab (Part 1b)
• Has known hypersensitivity to any component in the formulation of cemiplimab
• Has any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (\>10 mg daily prednisone equivalent)
• Has a condition requiring systemic treatment with corticosteroids
DRUG: ONM-501, DRUG: Cemiplimab
Triple Negative Breast Cancer, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Lymphoma, Non-Hodgkin, Mantle Cell Lymphoma, Bladder Cancer, Uveal Melanoma, Recurrent, Cervix Cancer, Carcinoma In Situ, Head and Neck Squamous Cell Carcinoma, Skin Cancer, Metastatic Cancer, Tumor, Solid, Tumor Recurrence, Anus, Bones and Joints, Brain and Nervous System, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Hodgkins Lymphoma, Kaposis sarcoma, Kidney, Lung/Thoracic, Lymphoid Leukemia, Melanoma, skin, Multiple Myeloma, Mycosis Fungoides, Non-Hodgkins Lymphoma, Other Digestive Organ, Other Endocrine System, Other Skin, Rectum, Small Intestine, Soft Tissue, Stomach, Urinary Bladder
Solid tumors, Lymphoma, ONM-501, STING, Intra-tumoral, HNSCC, Breast Cancer, Melanoma, Skin Cancer, cemiplimab, Libtayo, DLBCL, bladder cancer, cervical cancer, metastases, immunotherapy, ICI, TNBC, Triple Negative, mTNBC, anti-PD-1 antibody, BRCA1, BRCA2, anti-PD-L1, uveal, NHL, Mantle Zone lymphoma, FL, stimulator of interferon genes
UT Southwestern
A Study to Investigate the Safety and Tolerability of Ziftomenib in Combination with Venetoclax/Azacitidine, Venetoclax, or 7+3 in Patients with AML
This Phase 1 study will assess the safety, tolerability, and preliminary antileukemic activity of ziftomenib in combination with venetoclax and azacitidine (ven/aza), ven, and 7+3 for two different molecularly-defined arms, NPM1-m and KMT2A-r.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
ALL
18 Years and over
PHASE1
NCT05735184
STU-2023-0858
Key
Inclusion Criteria:
* Patients must have a documented NPM1 mutation or KMT2A rearrangement and have either newly diagnosed or relapsed/refractory AML
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
* Adequate liver, renal, and cardiac function according to protocol defined criteria
* A female of childbearing potential must agree to use adequate contraception from the time of screening through 180 days following the last dose of study intervention. A male of childbearing potential must agree to use abstinence or adequate contraception from the time of screening through 90 days following the last dose of study intervention
Key Exclusion Criteria:
* Diagnosis of either acute promyelocytic leukemia or blast chronic myelomonocytic leukemia
* Known history of BCR-ABL alteration
* Advanced malignant hepatic tumor \[for patients receiving ven/aza combination\]
* Administration of live attenuated vaccines within 14 days prior to, during, or after treatment until B-cell recovery
* Active central nervous system (CNS) involvement by AML.
* Clinical signs/symptoms of leukostasis or WBC \> 25,000 / microliter. Hydroxyurea and/or leukapheresis are permitted to meet this criterion
* Not recovered to Grade ≤1 (NCI-CTCAE v5.0) from all nonhematological toxicities except for alopecia
* Known clinically active human immunodeficiency virus, active hepatitis B or active hepatitis C infection
* For newly diagnosed cohorts: received prior chemotherapy for leukemia, except hydroxyurea and/or leukapheresis to control leukocytosis, prior treatment with all-transretinoic acid for initially suspected acute promyelocytic leukemia, or non-HMA therapy for prior myelodysplastic syndrome
* For relapsed/refractory cohorts: received chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy that is considered to be investigational \< 14 days prior to the first dose of ziftomenib or within 5 drug half-lives prior to the first dose of study drug
* Uncontrolled intercurrent illness including, but not limited to, cardiac illness as defined in the protocol
* Mean corrected QT interval corrected for heart rate by Fredericia's formula (QTcF) \>480 ms on triplicate ECGs
* Uncontrolled infection
* Women who are pregnant or lactating
* An active malignancy and currently receiving chemotherapy for that malignancy or disease that is uncontrolled/progressing DRUG: Ziftomenib, DRUG: Venetoclax, DRUG: Azacitidine, DRUG: Daunorubicin, DRUG: Cytarabine
Acute Myeloid Leukemia, Mixed Lineage Acute Leukemia, Mixed Lineage Leukemia Gene Mutation, Mixed Phenotype Acute Leukemia, Refractory AML, AML With Mutated NPM1, Acute Myeloid Leukemia Recurrent, Acute Myeloid Leukemia, in Relapse, NPM1 Mutation, KMT2Ar, Myeloid Sarcoma, Myeloid and Monocytic Leukemia
UT Southwestern
A Study of Revumenib in Combination With Chemotherapy for Patients Diagnosed With Relapsed or Refractory Leukemia
This phase II trial tests the safety and best dose of revumenib in combination with chemotherapy, and evaluates whether this treatment improves the outcome in infants and young children who have leukemia that has come back (relapsed) or does not respond to treatment (refractory) and is associated with a KMT2A (MLL) gene rearrangement (KMT2A-R). Leukemia is a cancer of the white blood cells, where too many underdeveloped (abnormal) white blood cells, called "blasts", are found in the bone marrow, which is the soft, spongy center of the bones that produces the three major blood cells: white blood cells to fight infection; red blood cells that carry oxygen; and platelets that help blood clot and stop bleeding. The blasts crowd out the normal blood cells in the bone marrow and spread to the blood. They can also spread to the brain, spinal cord, and/or other organs of the body. The leukemia cells of some children have a genetic change in which a gene (KMT2A) is broken and combined with other genes that typically do not interact with one another; this is called "rearranged". This genetic rearrangement alters how other genes are turned on or off in the cell, turning on genes that drive the development of leukemia. Patients with KMT2A rearrangement have higher risk for cancer coming back after treatment. Revumenib is an oral medicine that directly targets the changes that occur in a cell with a KMT2A rearrangement and has been shown to specifically kill these leukemia cells in preclinical laboratory settings and in animals. Drugs used in chemotherapy, such as vincristine, prednisone, asparaginase, fludarabine and cytarabine work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial is being done to find out if the combination of revumenib and chemotherapy would be safe and/or effective in treating infants and young children with relapsed or refractory KMT2A-R leukemia.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Caroline Smith
ALL
1 Month to 6 Years old
PHASE2
NCT05761171
STU-2023-1226
Inclusion Criteria:
* Patients must be 1 month to \< 6 years old at the time of study enrollment and must have had initial diagnosis of leukemia at \< 2 years old.
* Patients must have KMT2A-rearranged acute lymphoblastic leukemia (ALL), acute leukemia of ambiguous lineage (ALAL), or mixed phenotype acute leukemia (MPAL), which is determined to be refractory or in first marrow relapse. All patients must undergo cytogenetics and fluorescence in situ hybridization (FISH) testing of a relapsed/refractory blast sample at a Children's Oncology Group (COG)-approved laboratory for KMT2A-R status determination and the presence of a KMT2A- rearrangement must be confirmed by central review. Cytogenetics results must be submitted for central review by Day 10 of protocol therapy, for confirmation of KMT2A-R status. Patients enrolled with refractory disease may utilize initial diagnostic cytogenetics for eligibility and submission for central review if testing was performed at a COG approved laboratory. Patients will be eligible to remain on protocol therapy if KMT2A-R is confirmed by central review. Additional methods of assessing for KMT2A-R may be considered if FISH does not detect the rearrangement.
* Disease status at time of enrollment must be one of the following:
* First relapse (untreated): Any recurrence of marrow disease, with or without other extramedullary sites(s), at any point after achieving remission ("remission-1", per definition below) and meeting one of the below criteria. Patients must not have received any disease-directed therapy for the marrow relapse prior to enrollment, other than permitted cytoreduction.
* Relapse M1: M1 morphology (\< 5% blasts) + at least 2 confirmatory tests showing \>= 1% blasts (testing includes flow, cytogenetics, polymerase chain reaction \[PCR\]/next-generation sequencing \[NGS\] of immunoglobulin \[Ig\]/T-cell receptor \[TCR\] rearrangement, and/or PCR or NGS of fusion gene identical to diagnosis), OR
* Relapse M2: M2 morphology (5-25% blasts) + 1 confirmatory test showing \> 1% blasts, OR
* Relapse M3: M3 morphology (\> 25% blasts)
* Primary refractory, or failure to achieve remission-1: remission-1 is defined as \< 1% marrow blasts by flow MRD and resolution of extramedullary disease following at least 2 courses of frontline chemotherapy. Patients who receive 2 courses of chemotherapy and 1 course of blinatumomab are also eligible, but no further treatment attempts beyond that are permitted
* Central nervous system (CNS) disease: Patients must have CNS1 or CNS2 status and no clinical signs or neurologic symptoms suggestive of CNS leukemia, such as cranial palsy.
* Patients with CNS3 disease may receive antecedent intrathecal chemotherapy to achieve CNS1 or CNS2 status prior to enrollment.
* Patients with a history of CNS chloromatous disease are required to have no radiographic evidence of CNS disease prior to enrollment.
* White blood cell (WBC) must be \< 50,000/uL at the time of study enrollment. Patients can receive cytoreduction with hydroxyurea and/or corticosteroids for up to 7 days prior to enrollment.
* Patients \>= 12 months of age must have a performance status by Lansky Scale of \>= 50%.
* Patients must be able to take enteral medications. Acceptable routes of administration for revumenib (SNDX-5613) include: oral (PO), nasogastric (NG) tube, nasojejunal (NJ) tube, nasoduodenal (ND), and gastrostomy tube (G-tube).
* Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive:
* \>= 14 days must have elapsed after the completion of other cytotoxic therapy, including patients who relapse during pre-Maintenance upfront therapy, with these specific exceptions: cytoreduction with hydroxyurea and/or corticosteroids, and intrathecal chemotherapy, which have no required washout periods. For patients who relapse during upfront Maintenance therapy, \>= 7 days must have elapsed after the last dose of chemotherapy. Additionally, patients must have fully recovered from all acute toxic effects of prior therapy.
* NOTE: Cytoreduction with hydroxyurea and/or corticosteroids is permitted prior to enrollment for patients with WBC \>= 50,000/uL, and by provider discretion regardless of WBC, to reduce potential risk of differentiation syndrome with revumenib initiation. Hydroxyurea and/or corticosteroids may be given for up to 7 days, with no wash-out required.
* NOTE: No waiting period is required for patients having received intrathecal cytarabine, methotrexate, and/or hydrocortisone. Intrathecal chemotherapy that is given up to 7 days prior to the initiation of protocol therapy counts as protocol therapy and not prior anti-cancer therapy. Intrathecal chemotherapy given \> 7 days prior does not count as protocol therapy.
* NOTE: Prior exposure to fludarabine and cytarabine (FLA) is permitted.
* Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): \>= 7 days after the last dose of agent.
* Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1. There is an exception for blinatumomab infusions, for which patients must have been off for at least 3 days and all drug related toxicity must have resolved to grade 2 or lower as outlined in the inclusion/exclusion criteria.
* Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or \>= 7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator.
* Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon, or cytokines
* Stem cell infusions (with or without total body irradiation (TBI):
* Allogeneic (non-autologous) bone marrow or stem cell transplant, or stem cell boost: \>= 84 days after infusion
* Donor leukocyte infusion: \>= 28 days
* Cellular therapy: \>= 28 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.)
* Radiation therapy (XRT)/external beam irradiation including protons: \>= 14 days after local XRT; \>= 84 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial bone marrow radiation.
* A creatinine based on age as follows:
* Age 1 month to \< 6 months: maximum creatinine 0.4 mg/dL
* Age 6 months to \< 1 year: maximum creatinine 0.5 mg/dL
* Age 1 to \< 2 years: maximum creatinine 0.6 mg/dL
* Age 2 to \< 6 years: maximum creatinine 0.8 mg/dL OR
* a 24-hour urine creatinine clearance \>= 70 mL/min/1.73 m\^2 OR
* a glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard).
* NOTE: Estimated GFR (eGFR) from creatinine, cystatin C or other estimates are not acceptable for determining eligibility.
* A direct bilirubin =\< 1.5 x upper limit of normal (ULN) for age, unless disease related
* Serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (3 x ULN) unless disease related.
* Note: For the purpose of eligibility, the ULN for SGPT (ALT) has been set to the value of 45 U/L
* Shortening fraction of \>= 27% by echocardiogram, or ejection fraction of \>= 50% by radionuclide angiogram.
* Corrected QT interval using Fridericia formula (QTcF) of \< 450 msec (using the average of triplicate measurements)
* NOTE: There are no specific electrolyte parameters for eligibility. However, it should be noted that, to limit QTc prolongation risk, patients must maintain adequate potassium and magnesium levels to initiate and continue revumenib (SNDX-5613) on protocol therapy.
* Patients must be able to comply with the safety monitoring requirements of the study, in the opinion of the treating investigator.
Exclusion Criteria:
* Patients with isolated extramedullary leukemia.
* Patients diagnosed with Down syndrome.
* Patients known to have one of the following syndromes:
* Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or any other known bone marrow failure syndrome.
* Patients with a secondary KMT2A-R leukemia that developed after treatment of prior malignancy with cytotoxic chemotherapy.
* Patients with a history of congenital prolonged QT syndrome, congestive heart failure or uncontrolled arrhythmia in the past 6 months prior to study enrollment.
* Patients with an active, uncontrolled infection, further defined below:
* Positive bacterial blood culture within 48 hours of study enrollment
* Fever above 38.2 degrees Celsius (C) within 48 hours of study enrollment with clinical signs of infection. Fever that is determined to be due to tumor burden is allowed if patients have documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability
* A positive fungal culture within 30 days of study enrollment or active therapy for presumed invasive fungal infection
* Patients may be receiving IV or oral antibiotics to complete a course of therapy for a prior documented infection as long as cultures have been negative for at least 48 hours and signs or symptoms of active infection have resolved. For patients with Clostridium (C.) difficile diarrhea, at least 72 hours of antibacterial therapy must have elapsed and stools must have normalized to baseline
* Active viral or protozoal infection requiring IV treatment
* Human immunodeficiency virus (HIV)-infected patients are eligible if on effective anti-retroviral therapy that does not interact with planned study agents and with undetectable viral load within 6 months of enrollment.
* Patients with active acute graft-versus-host disease (GVHD) \> grade 0 (unless skin only), or chronic GVHD \> mild (unless skin only) are not eligible. Patients with acute or chronic skin GVHD that is =\< grade 1, or chronic skin GVHD that is graded as mild are eligible.
* Patients who have received a prior solid organ transplantation.
* Patients with known Charcot-Marie-Tooth disease, if treating on Regimen A (with vincristine).
* CYP3A4 Inhibitors or Inducers: Patients who require concomitant therapy with strong CYP3A4 inhibitors or moderate or strong CYP3A4 inducers, as these are prohibited during the chemotherapy combination cycles. These agents should be discontinued at least 5 half-lives prior to starting protocol therapy. Concomitant use of strong CYP3A4 inhibitor -azole antifungals are permitted during the revumenib (SNDX-5613) monotherapy cycles, with appropriate revumenib (SNDX-5613) dose modification
* P-glycoprotein (P-gp) inhibitors or inducers: Vincristine is a substrate for P-gp. Concomitant use of P-gp inhibitors or inducers with vincristine (patients receiving Regimen A Cycle 1) should be avoided.
* Investigational drugs: Patients who are currently receiving another investigational drug.
* Anti-cancer agents: Patients who are currently receiving other anti-cancer agents (exceptions: hydroxyurea and corticosteroids, which may be used as cytoreduction prior to enrollment).
* Anti-GVHD agents: Patients who are receiving cyclosporine, tacrolimus, or other systemic agents to treat graft-versus-host disease post bone marrow transplant. Patients should discontinue anti-GVHD agents \> 7 days prior to enrollment and have no evidence of worsening GVHD. Topical steroids are permitted.
* Patients who have previously been treated with revumenib (SNDX-5613). Prior exposure to other menin inhibitors is permitted.
* All patients and/or their parents or legal guardians must sign a written informed consent.
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met. PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, DRUG: Calaspargase Pegol, DRUG: Cytarabine, PROCEDURE: Echocardiography, DRUG: Fludarabine Phosphate, DRUG: Hydrocortisone Sodium Succinate, PROCEDURE: Lumbar Puncture, DRUG: Methotrexate, PROCEDURE: Multigated Acquisition Scan, DRUG: Prednisolone, DRUG: Prednisone, DRUG: Revumenib, DRUG: Vincristine Sulfate
Recurrent Acute Leukemia of Ambiguous Lineage, Recurrent Acute Lymphoblastic Leukemia, Recurrent Acute Myeloid Leukemia Due to Lineage Switch From Acute Leukemia of Ambiguous Lineage, Recurrent Acute Myeloid Leukemia Due to Lineage Switch From B Acute Lymphoblastic Leukemia, KMT2A-Rearranged, Recurrent Acute Myeloid Leukemia Due to Lineage Switch From Mixed Phenotype Acute Leukemia, Recurrent Mixed Phenotype Acute Leukemia, Refractory Acute Leukemia of Ambiguous Lineage, Refractory Acute Lymphoblastic Leukemia, Refractory Acute Myeloid Leukemia Due to Lineage Switch From Acute Leukemia of Ambiguous Lineage, Refractory Acute Myeloid Leukemia Due to Lineage Switch From B Acute Lymphoblastic Leukemia, KMT2A-Rearranged, Refractory Acute Myeloid Leukemia Due to Lineage Switch From Mixed Phenotype Acute Leukemia, Refractory Mixed Phenotype Acute Leukemia, Leukemia, Not Otherwise Specified, Leukemia, Other
Children’s Health
A Study of an MMSET Inhibitor in Patients With Relapsed and Refractory Multiple Myeloma
A Phase I study to evaluate the safety of a novel, orally available, selective, and potent small molecule inhibitor of the histone lysine methyl transferase MMSET (also known as NSD2/WHSC1) to prevent the dimethylation of H3K36 in adult patients with relapsed or refractory multiple myeloma (RRMM).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Aimaz Afrough
All
18 Years and over
Phase 1
NCT05651932
STU-2023-0538
Key
• ≥ 18 years of age
• ECOG score ≤ 2
• Relapsed or refractory multiple myeloma (as per IMWG)
• ≥ 3 prior lines of therapy, including a PI, an IMiD, and an anti-CD38 antibody
• Patients must have exhausted available therapeutic options that are expected to provide a meaningful clinical benefit, either through disease relapse, treatment refractory disease, intolerance, or refusal of the therapy
• t(4;14) confirmed by standard of care FISH testing, or GOF mutation in MMSET confirmed by local sequencing test (Part B dose expansion cohorts only)
• Measurable disease, including at least 1 of the following criteria:
• Serum M protein ≥ 0.50 g/dL (by SPEP)
• Serum IgA ≥ 0.50 g/dL (IgA myeloma patients)
• Urine M protein ≥ 200 mg/24 h (by UPEP)
• sFLC involved light chain ≥ 10 mg/dL (100 mg/L) (patients with abnormal sFLC ratio)
• ≥ 1 extramedullary lesion ≥ 1 cm in size and able to be followed by imaging assessments (Part A dose escalation cohorts only)
• Bone marrow plasma cells ≥ 10% (Part A dose escalation cohorts only) Key
• Treatment with the following therapies in the specified time period prior to first dose:
• Radiation, chemotherapy, immunotherapy, or any other anticancer therapy ≤ 2 weeks
• Cellular therapies ≤ 8 weeks
• Autologous transplant < 100 days
• Allogenic transplant ≤ 6 months, or > 6 months with active GVHD
• Major surgery ≤ 4 weeks
• History of or current plasma cell leukemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, and skin changes) syndrome, solitary bone lesion or bone lesions as the only evidence for plasma cell dyscrasia, myelodysplastic syndrome or a myeloproliferative neoplasm or light chain amyloidosis
• Active CNS disease
• Inadequate bone marrow function
• Inadequate renal, hepatic, pulmonary, and cardiac function
• Active, ongoing, or uncontrolled systemic viral, bacterial, or fungal infection. Permitted prophylactic medications, antimicrobials or antiretroviral therapies defined in protocol.
• Use of acid reducing agents and strong inhibitors or inducers of CYP3A4 within 14 days or 5 half-lives prior to first dose
• Active malignancy not related to myeloma requiring therapy within < 3 years prior to enrollment, or not in complete remission, with exceptions defined in protocol.
Inclusion Criteria:
• ≥ 18 years of age
• ECOG score ≤ 2
• Relapsed or refractory multiple myeloma (as per IMWG)
• ≥ 3 prior lines of therapy, including a PI, an IMiD, and an anti-CD38 antibody
• Patients must have exhausted available therapeutic options that are expected to provide a meaningful clinical benefit, either through disease relapse, treatment refractory disease, intolerance, or refusal of the therapy
• t(4;14) confirmed by standard of care FISH testing, or GOF mutation in MMSET confirmed by local sequencing test (Part B dose expansion cohorts only)
• Measurable disease, including at least 1 of the following criteria:
• Serum M protein ≥ 0.50 g/dL (by SPEP)
• Serum IgA ≥ 0.50 g/dL (IgA myeloma patients)
• Urine M protein ≥ 200 mg/24 h (by UPEP)
• sFLC involved light chain ≥ 10 mg/dL (100 mg/L) (patients with abnormal sFLC ratio)
• ≥ 1 extramedullary lesion ≥ 1 cm in size and able to be followed by imaging assessments (Part A dose escalation cohorts only)
• Bone marrow plasma cells ≥ 10% (Part A dose escalation cohorts only) Key
Exclusion Criteria:
• Treatment with the following therapies in the specified time period prior to first dose:
• Radiation, chemotherapy, immunotherapy, or any other anticancer therapy ≤ 2 weeks
• Cellular therapies ≤ 8 weeks
• Autologous transplant < 100 days
• Allogenic transplant ≤ 6 months, or > 6 months with active GVHD
• Major surgery ≤ 4 weeks
• History of or current plasma cell leukemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, and skin changes) syndrome, solitary bone lesion or bone lesions as the only evidence for plasma cell dyscrasia, myelodysplastic syndrome or a myeloproliferative neoplasm or light chain amyloidosis
• Active CNS disease
• Inadequate bone marrow function
• Inadequate renal, hepatic, pulmonary, and cardiac function
• Active, ongoing, or uncontrolled systemic viral, bacterial, or fungal infection. Permitted prophylactic medications, antimicrobials or antiretroviral therapies defined in protocol.
• Use of acid reducing agents and strong inhibitors or inducers of CYP3A4 within 14 days or 5 half-lives prior to first dose
• Active malignancy not related to myeloma requiring therapy within < 3 years prior to enrollment, or not in complete remission, with exceptions defined in protocol.
Drug: KTX-1001
Multiple Myeloma, Myeloma, Myeloma Multiple, Myeloid and Monocytic Leukemia
NSD2, MMSET, WHSC1, T4,14, T(4,14), translocation, myeloma, RRMM
UT Southwestern
Canakinumab for the Prevention of Progression to Cancer in Patients with Clonal Cytopenias of Unknown Significance, IMPACT Study
This phase II trial tests how well canakinumab works to prevent progression to cancer in patients with clonal cytopenias of unknown significance (CCUS). CCUS is a blood condition defined by a decrease in blood cells. Blood cells are composed of either red blood cells, white blood cells, or platelets. In patients with CCUS, blood counts have been low for a long period of time. Patients with CCUS also have a mutation in one of the genes that are responsible for helping blood cells develop. The combination of genetic mutations and low blood cell counts puts patients with CCUS at a higher risk to develop blood cancers in the future. This transformation from low blood cell counts to cancer may be caused by inflammation in the body. Canakinumab is a monoclonal antibody that may block inflammation in the body by targeting a specific antibody called the anti-human interleukin-1beta (IL-1beta).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
ALL
18 Years to old
PHASE2
NCT05641831
STU-2024-0699
Inclusion Criteria:
* Patients with age \>= 18 with high-risk CCUS
* Must meet ALL the following criteria:
* Unexplained, clinically meaningful cytopenias (greater than 4 months) in one or more of the following lineages: erythroid cells, neutrophils, platelets. Clinically meaningful cytopenia is institution specific and threshold may vary on age, sex, and race. Decision-making should depend upon lab values specific to the institution and supersede public works. Based upon published work, significant cytopenias are defined as the following:
* Erythroid Cells:
* Hemoglobin \< 11 g/dL
* White Blood Cells:
* Absolute Neutrophil Count \< 1800/microL and \> 500/microL
* Platelets:
* Platelet Count \< 150,000/microL and \> 50,000/microL
* MDS criteria not fulfilled
* No other evidence of hematological malignancy
* No or only mild (\< 10%) bone marrow dysplasia
* Blast cells \< 5% detected via morphologic examination of blood and/or bone marrow smears which can also be supported by flow cytometry and/or immunohistochemical studies
* Any of the following:
* Isolated somatic spliceosome mutation at any VAF (SRSF2, SF3B1, U2AF1, or ZRSR2)
* Isolated TP53 mutation greater than 5% VAF
* At least 1 mutation in TET2, DMNT3A, or ASXL1 at any VAF coupled with at least 1 other known myeloid pathogenic somatic mutation or known pathogenic germline mutation that predisposes to myeloid malignancy as determined by next generation sequencing and bone marrow biopsy
* A TET2, DMNT3A, or ASXL1 greater than 10% VAF coupled with another TET2, DMNT3A, or ASXL1 greater than 10% VAF
* The presence of two or more known myeloid pathogenic somatic or germline mutations (other than TET2, ASXL1, DMNT3A, TP53, or spliceosome mutations) greater than 10% VAF
* Ability to understand and willingness to sign the written informed consent document
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
* Patients with a history of hypertension or active hypertension are strongly encouraged to optimize blood pressure control
* Creatinine clearance greater than 45 ml/min using Cockcroft-Gault
* Total bilirubin =\< 1.5 x ULN
* Aspartate transaminase (AST) \< 3 x ULN
* Alanine transaminase (ALT) \< 3 x ULN
Exclusion Criteria:
* Concurrent malignancy requiring active systemic therapy
* Diagnosis of MDS or any other myeloid malignancy in the patient's lifetime
* History of Hypersensitivity to canakinumab or drug of a similar class
* Active infection requiring prompt evaluation and treatment or history of recurrent infections
* Known active or recurrent hepatic disorder including cirrhosis, hepatitis B and C (via positive or indeterminate central laboratory \[lab\] results)
* Subjects with active tuberculosis. In subjects without active tuberculosis, if the results of the evaluation require treatment per local guidelines, then the treatment should be initiated before randomization (unless otherwise required by Health Authorities or Institutional Review Board (IRB) in which case curative treatment must be completed prior to screening)
* Subjects with suspected or proven immunocompromised state or infections. If the results of this screening per local treatment guidelines or clinical practice require treatment for said infection then the patient is not eligible. Suspected or proven immunocompromised states or infections include:
* Those with any other medical condition such as active infection, treated or untreated, which in the opinion of the investigator places the subject at an unacceptable risk for participation in immunomodulatory therapy
* Known history of testing positive for human immunodeficiency virus (HIV) infections. For countries where HIV status is mandatory: testing positive for HIV during screening using a local test.
* Allogeneic bone marrow or solid organ transplant (history of any or within a certain period of time?)
* Those requiring systemic or local treatment with any immune modulating agent in doses with systemic effects e.g.:
* Prednisone \> 20 mg (or equivalent) oral or intravenous daily for \> 14 days
* Prednisone \> 5 mg and =\< 20 mg (or equivalent) daily for \> 30 days
* Equivalent dose of methotrexate \> 15 mg weekly
* Note: Azathioprine is allowed. Daily glucocorticoid-replacement for conditions such as adrenal or pituitary insufficiency is allowed. Topical, inhaled or local steroid use in doses that are not considered to cause systemic effects are permitted. Steroids for pre-medication related to chemotherapy as per local standard of care are permitted.
* Live or attenuated vaccination within 3 months prior to first dose of study drug (e.g. Measles/Mumps/Rubella \[MMR\], Yellow Fever, Rotavirus, Smallpox, etc.) and after initiation of canakinumab treatment
* Use of erythropoietin stimulating agents (ESA) or growth factors within four weeks prior to the start of the study
* Pregnant or nursing women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using basic methods of contraception during dosing of study treatment and for up to 130 days after last dose of study drug. Basic contraception methods include:
* Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least 6 weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
* Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject
* Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps). For UK: with spermicidal foam/gel/film/cream/ vaginal suppository
* Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate \< 1%), for example hormone vaginal ring or transdermal hormone contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS). In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. Prior to entry into this study, cisplatin-based chemotherapy, which may be toxic to the fetus, may be given. The time between the end of cisplatin-based chemotherapy and the start canakinumab/placebo treatment is variable, resulting in a variable need for continuation of highly effective contraception. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (i.e. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least six weeks prior to first dose of study drug. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the Informed Consent Form (ICF). PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration and Biopsy, DRUG: Canakinumab, PROCEDURE: Chest Radiography, PROCEDURE: Echocardiography, DRUG: Placebo Administration, OTHER: Quality-of-Life Assessment
Clonal Cytopenia of Undetermined Significance, Myeloid and Monocytic Leukemia, Leukemia, Not Otherwise Specified, Leukemia, Other
UT Southwestern
Studying the Effect of Levocarnitine in Protecting the Liver From Chemotherapy for Leukemia or Lymphoma
This phase III trial compares the effect of adding levocarnitine to standard chemotherapy versus (vs.) standard chemotherapy alone in protecting the liver in patients with leukemia or lymphoma. Asparaginase is part of the standard of care chemotherapy for the treatment of acute lymphoblastic leukemia (ALL), lymphoblastic lymphoma (LL), and mixed phenotype acute leukemia (MPAL). However, in adolescent and young adults (AYA) ages 15-39 years, liver toxicity from asparaginase is common and often prevents delivery of planned chemotherapy, thereby potentially compromising outcomes. Some groups of people may also be at higher risk for liver damage due to the presence of fat in the liver even before starting chemotherapy. Patients who are of Japanese descent, Native Hawaiian, Hispanic or Latinx may be at greater risk for liver damage from chemotherapy for this reason. Carnitine is a naturally occurring nutrient that is part of a typical diet and is also made by the body. Carnitine is necessary for metabolism and its deficiency or absence is associated with liver and other organ damage. Levocarnitine is a drug used to provide extra carnitine. Laboratory and real-world usage of the dietary supplement levocarnitine suggests its potential to prevent or reduce liver toxicity from asparaginase. The overall goal of this study is to determine whether adding levocarnitine to standard of care chemotherapy will reduce the chance of developing severe liver damage from asparaginase chemotherapy in ALL, LL and/or MPAL patients.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kathleen Ludwig
ALL
15 Years to 40 Years old
PHASE3
NCT05602194
STU-2023-1026
Inclusion Criteria:
* \>= 15 and \< 40 years at time of diagnosis
* Newly diagnosed B-ALL, T-ALL, lymphoblastic lymphoma (LLy), or mixed-phenotype acute leukemia/lymphoma (MPAL)
* Note: Philadelphia chromosome (PH)+ and PH-like acute leukemia are eligible (use of tyrosine kinase inhibitors \[TKI\] or CRLF2- targeted concomitant medication must be documented, if used)
* Conjugated bilirubin =\< 1.5 x upper limit of normal (ULN) for age, regardless of baseline bilirubin (within 7 days prior to enrollment), and
* Serum glutamate pyruvate transaminase (SGPT) (ALT) =\< 225 U/L (=\< 5x ULN) (within 7 days prior to enrollment), and
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L and serum glutamic oxaloacetic transaminase (SGOT) (AST) to 50 U/L regardless of baseline
* SGOT (AST) =\< 250 U/L (=\< 5x ULN) (within 7 days prior to enrollment)
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L and SGOT (AST) to 50 U/L regardless of baseline
* For patients receiving ursodiol prior to enrollment, laboratory values must meet above criteria off ursodiol for 7 days
* PEDIATRIC PATIENTS (AGE 15-17 years):
* A 24-hour urine creatinine clearance \>= 30 mL/min/1.73 m\^2 (within 7 days prior to enrollment) OR
* A glomerular filtration rate (GFR) \>= 30 mL/min/1.73 m\^2. GFR must be performed using one of the following methods (within 7 days prior to enrollment):
* 1. Estimated GFR (eGFR) \>= 30 mL/min/1.73 m\^2.
* An online calculator is available through the National Kidney Foundation at https://www.kidney.org/professionals/kdoqi/gfr_calculatorped
* 2. Measured GFR \>= 30 mL/min/1.73 m\^2 (any age). If measured GFR is used, it must be performed using direct measurement with a nuclear blood sampling method or small molecule clearance method (iothalamate or other molecule per institutional standard).
* ADULT PATIENTS (AGE 18 YEARS OR OLDER): Creatinine clearance \>= 30 mL/min, as estimated by the Cockcroft and Gault formula or a 24-hour urine collection (within 7 days prior to enrollment). Estimated creatinine clearance is based on actual body weight
* An online calculator is available through the National Kidney Foundation at https://www.kidney.org/professionals/kdoqi/gfr_calculatorcoc
* Berlin-Frankfurt-Munich (BFM), Children's Oncology Group (COG), or C10403-based Induction regimen and must be inclusive of \>= 1 dose of pegaspargase or calaspargase pegol, and
* First dose of asparaginase must be planned within the first week of induction therapy, and
* Dose of pegaspargase or calaspargase pegol must be \>= 1,000 IU/ m\^2 (dose-capping permitted per primary regimen)
* Note: Co-enrollment on a therapeutic consortia trial is not required
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
* Down syndrome
* Known inherited or autoimmune liver disease impacting conjugated bilirubin (e.g., Alagille syndrome, primary sclerosing cholangitis, other)
* Known biopsy (or imaging) proven severe liver fibrosis (Batts-Ludwig \>= stage 3)
* Unable to tolerate oral formulation of study drug at enrollment
* Patients who received chemotherapy or treatment for a prior malignancy are not eligible
* The following are permitted: steroid prophase, hydroxyurea, or other cytoreduction prior to initiation of Induction chemotherapy (must be documented) and chemotherapy for current diagnosis (i.e. initiation of Induction therapy within enrollment window). Chemotherapy prior to enrollment for treatment of a non-malignancy (e.g., steroid or methotrexate for autoimmune disease) is also permitted and must be documented
* Female patients who are pregnant since fetal toxicities and teratogenic effects in humans are unknown for study drug. A pregnancy test is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation PROCEDURE: Biospecimen Collection, DRUG: Calaspargase Pegol, DIETARY_SUPPLEMENT: Levocarnitine, DRUG: Pegaspargase, OTHER: Quality-of-Life Assessment
B Acute Lymphoblastic Leukemia, B Acute Lymphoblastic Leukemia With t(9,22)(q34.1,q11.2), BCR-ABL1, B Acute Lymphoblastic Leukemia, BCR-ABL1-Like, Lymphoblastic Lymphoma, Mixed Phenotype Acute Leukemia, T Acute Lymphoblastic Leukemia, Lymphoid Leukemia, Lymphoma
Children’s Health
Study of SGR-1505 in Mature B-Cell Neoplasms
The purpose of this study is to evaluate safety and tolerability and to determine the maximum tolerated dose (MTD) and/or recommended dose (RD) of SGR-1505.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Heather Wolfe
All
18 Years and over
Phase 1
NCT05544019
STU-2023-0636
Inclusion Criteria:
• Subject must have a history of histologically or cytologically confirmed mature B-cell malignancy.
• Subject must have measurable or detectable disease according to the applicable disease-specific classification system.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Life expectancy ≥ 12 weeks.
Exclusion Criteria:
• For a subject with indolent NHL and CLL/SLL, the subject is in need of immediate cytoreductive therapy (unless the patient has no remaining treatment choice with potential benefit) and has an indication for treatment.
• Subject has previous invasive malignancy in the last 2 years.
• Subject has a known allergy to SGR-1505 or excipients of SGR-1505.
• Subject has symptomatic or active CNS involvement of disease.
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that would place the participant at increased risk to the use of an investigational drug.
Drug: SGR-1505
Mature B-Cell Neoplasm, Non Hodgkin Lymphoma, DLBCL, Waldenström Macroglobulinemia, MALT Lymphoma, Follicular Lymphoma, Pediatric-Type Follicular Lymphoma, IRF4 Gene Rearrangement, EBV-Positive DLBCL, Nos, Burkitt Lymphoma, Plasmablastic Lymphoma, High-grade B-cell Lymphoma, Primary Cutaneous Follicle Center Lymphoma, Primary Effusion Lymphoma, Mantle Cell Lymphoma, DLBCL Germinal Center B-Cell Type, Primary Mediastinal Large B Cell Lymphoma, T-Cell/Histiocyte Rich Lymphoma, ALK-Positive Large B-Cell Lymphoma, Primary Cutaneous Diffuse Large B-Cell Lymphoma, Splenic Marginal Zone Lymphoma, Chronic Lymphocytic Leukemia, Nodal Marginal Zone Lymphoma, HHV8-Positive DLBCL, Nos, Lymphoplasmacytic Lymphoma, Duodenal-Type Follicular Lymphoma, Lymphoid Leukemia, Non-Hodgkins Lymphoma
MALT1, NF-kB
UT Southwestern
Venetoclax and Azacitidine for Treatment of Therapy Related or Secondary Myelodysplastic Syndrome
This phase II trial studies the effect of venetoclax and azacitidine in treating patients with therapy related or secondary myelodysplastic syndrome. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Chemotherapy drugs, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax in combination with azacitidine may work better in treating patients with therapy related or secondary myelodysplastic syndrome.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
ALL
18 Years and over
PHASE2
NCT05379166
STU-2022-0513
Inclusion Criteria:
* Ability to understand and the willingness to sign a written informed consent document
* Age \>= 18 years at time of informed consent. Both men and women and members of all races and ethnic groups will be included
* Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2
* Previously untreated therapy related myelodysplastic syndrome (t-MDS) with Revised International Prognostic Scoring System (IPSS-R) risk categories Intermediate, High or Very High (i.e., minimum IPSS-R score of 3.5) and presence of \< 20% bone marrow blasts per bone marrow biopsy/aspirate
* Patients with t-MDS which is defined as patients who have had prior anti-cancer therapy including chemotherapy and/or radiation therapy
* Aspartate aminotransferase (AST) \< 3.0 x upper limit of normal (ULN) x upper limit of normal (ULN; local laboratory)
* Alanine aminotransferase (ALT) \< 3.0 x ULN x ULN
* Total bilirubin =\< 2 x ULN (except for patients with known Gilbert's syndrome)
* Creatinine clearance \>= 30 mL/min OR serum creatinine \< 1.5 x the ULN
* White blood cell (WBC) count =\< 10,000/uL
* Note: Treatment with hydroxyurea is permitted to lower the WBC to reach this inclusion criterion. The WBC should be determined \>= 24 hours after the last dose of hydroxyurea. The last dose of hydroxyurea should not be administered =\< 3 days prior to the first dose of azacitidine
* Females of childbearing potential (FOCBP) must agree to adequate contraception (1 form of contraception or abstinence) from the screening visit until 30 days following the last dose of venetoclax. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
* FOCBP are those who have not been surgically sterilized or have not been free from menses for \> 1 year without an alternative medical cause
* Male patients of childbearing potential having intercourse with females of childbearing potential must agree to abstain from heterosexual intercourse or have their partner use 2 forms of contraception from the screening visit until 90 days after the last dose of study treatment. They must also refrain from sperm donation from the screening visit until 90 days following the last dose of study treatment
Exclusion Criteria:
* Participant has received prior therapy with a venetoclax or other BH3 mimetic. Note: Prior supportive care in form of transfusions or growth factors, etc., is not considered prior therapy. Supportive care should be discontinued \>= 14 days prior to the first dose of study drug. Subjects may continue oral corticosteroids for management of conditions other than MDS (e.g., asthma, rheumatoid arthritis) at a stable daily dose equivalent to =\< 10 mg prednisone during screening and study participation
* Subject has a diagnosis other than previously untreated de novo MDS with IPSS-R risk categories Intermediate, High or Very High, including:
* MDS with IPSS-R risk categories Very Low or Low (overall IPSS score \< 3)
* MDS evolving from a pre-existing myeloproliferative neoplasm (MPN)
* MDS/MPN including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (CML), juvenile myelomonocytic leukemia (JMML) and unclassifiable MDS/MPN
* Patients who are suitable for and willing to receive intensive chemotherapy or eligible to proceed to allogeneic stem cell transplantation without additional therapy
* Known history of testing positive for Human Immunodeficiency Virus (HIV) infections, Hepatitis B, or Hepatitis C. For countries where HIV status is mandatory: testing positive for HIV during screening using a local test.
* Clinically significant ventricular arrhythmia (e.g., ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
* Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure
* Patients with uncontrolled infection will not be enrolled until infection is treated and under control
* Hypersensitivity to any study agent when administered alone. Any concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the patient or compliance with the protocol
* Any psychiatric illness that prevents patient from informed consent process
* Pregnant of breastfeeding at the time of enrollment
* Subject has received allogeneic HSCT or solid organ transplantation
* Subject has a concurrent active malignancy requiring treatment or with an expected life expectancy less than 1 year with the exception of below. Any subject with a concurrent active malignancy will be reviewed by the PI for eligibility prior to enrollment
* Adequately treated in situ carcinoma of the cervix uteri
* Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin
* Asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy
* Subject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
* Ongoing systemic infection (viral, bacterial, or fungal)
* Acute pneumonia
* Febrile neutropenia
* Subject has received strong or moderate CYP3A inducers within 7 days prior to the first dose of study drug
* Subject has received strong or moderate CYP3A inhibitors within 7 days prior to the first dose of study drug
* Subject has consumed one or more of the following within 3 days prior to the first dose of study drug:
* Grapefruit or grapefruit products
* Seville oranges (including marmalade containing Seville oranges)
* Star fruit (carambola)
* Subject has a malabsorption syndrome or other condition that precludes an enteral route of administration
* Subject has history of a cardiovascular, endocrinologic, hepatic, immunologic metabolic, neurologic, psychiatric, pulmonary, renal disease, or any other condition that in the opinion of the investigator would adversely affect his/her participation in this study or interpretation of study results
* Subject has received a live attenuated vaccine within 4 weeks prior to the first dose of study drug DRUG: Azacitidine, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration, DRUG: Venetoclax
Secondary Myelodysplastic Syndrome, Therapy-Related Myelodysplastic Syndrome, Myeloid and Monocytic Leukemia
UT Southwestern
Venetoclax in Children With Relapsed Acute Myeloid Leukemia (AML)
A study to evaluate if the randomized addition of venetoclax to a chemotherapy backbone (fludarabine/cytarabine/gemtuzumab ozogamicin \[GO\]) improves survival of children/adolescents/young adults with acute myeloid leukemia (AML) in 1st relapse who are unable to receive additional anthracyclines, or in 2nd relapse.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kathleen Ludwig
ALL
29 Days to 21 Years old
PHASE3
NCT05183035
STU-2022-0725
Inclusion Criteria
* Participants must have enrolled on APAL2020SC, NCT Number: NCT04726241 prior to enrollment on ITCC-101/APAL2020D. (This is only applicable for participants in USA/Canada/Australia/New Zealand sites/LLS territory).
* Participants must be ≥ 29 days of age and ≤ 21 years of age at enrollment.
* Participants must have one of the following:
* Children, adolescents, and young adults with acute myeloid leukemia without FLT3/internal tandem duplication (ITD) mutation in:
• Second relapse, who are sufficiently fit to undergo another round of intensive chemotherapy
• First relapse who per investigator discretion cannot tolerate additional anthracycline containing chemotherapy. * Participants must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2 (≥ 50% Lansky or Karnofsky score) * Participants must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to start of protocol treatment:
• Cytotoxic chemotherapy: Must not have received cytotoxic chemotherapy within 14 days prior to start of protocol treatment, except for corticosteroids, low dose cytarabine or hydroxyurea that can be given up to 24 hours prior to start of protocol treatment.
• Intrathecal cytotoxic therapy: No wash-out time is required for participants having received any combination of intrathecal cytarabine, methotrexate, and/or hydrocortisone.
• Antibodies: ≥ 21 days must have elapsed from infusion of last dose of an antibody-drug conjugate before start of protocol treatment. For unmodified antibodies or T cell engaging antibodies, 2 half-lives must have elapsed before start of protocol treatment. Any toxicity related to prior antibody therapy must be recovered to Grade ≤ 1.
• Interleukins, Interferons and Cytokines (other than Hematopoietic Growth Factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than Hematopoietic Growth Factors) before start of protocol treatment.
• Hematopoietic growth factors: ≥ 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or ≥7 days for short-acting growth factor before start of protocol treatment.
• Radiation therapy (RT) (before start of protocol treatment): * ≥ 14 days have elapsed for local palliative RT (small port); * ≥ 84 days must have elapsed if prior craniospinal RT or if ≥ 50% radiation of pelvis; * ≥ 42 days must have elapsed if other substantial bone marrow (BM) radiation.
• Stem Cell Infusions (before start of protocol treatment): * ≥ 84 days since allogeneic (non-autologous) bone marrow or stem cell transplant (with or without total body irradiation \[TBI\]) or boost infusion (any stem cell product; not including donor lymphocyte infusion \[DLI\]) * No evidence of active graft versus host disease (GVHD).
• Participants who are receiving cyclosporine, tacrolimus or other agents to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial. Participants must be off medications to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant for at least 14 days prior to enrollment.
• Cellular Therapy: ≥ 42 days after the completion of donor lymphocyte infusion (DLI) or any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.) before start of protocol treatment.
• Participants with prior exposure to venetoclax are eligible in this trial * Adequate organ function:
• Adequate Renal Function defined as: * Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 60ml/min/1.73 m\^2, or * Normal serum creatinine based on age/sex
• Adequate Liver Function defined as: * Direct bilirubin \< 1.5 x upper limit of normal (ULN), and * Alkaline phosphatase ≤ 2.5 x ULN, and * Serum glutamic pyruvic transaminase (SGPT) alanine aminotransferase (ALT) ≤ 2.5 x ULN. If liver abnormality is due to radiographically identifiable leukemia infiltrate, the participant will remain eligible.
• Cardiac performance: Minimum cardiac function defined as: * No history of congestive heart failure in need of medical treatment * No pre-treatment diminished left ventricular function on echocardiography (shortening fraction \[SF\] \< 25% or ejection fraction \[EF\] \< 40%) * No signs of congestive heart failure at presentation of relapse. * Participant, parent or guardian must sign and date informed consent and pediatric assent (when required), prior to the initiation of screening or study specific procedures, according to local law and legislation. Exclusion Criteria * Participants who in the opinion of the investigator may not be able to comply with the study requirements of the study, are not eligible. * Participants with Down syndrome. * Participants with Acute promyelocytic leukemia (APL) or Juvenile myelomonocytic leukemia (JMML). * Participants with isolated CNS3 disease or symptomatic CNS3 disease. * Participants with malabsorption syndrome or any other condition that precludes enteral administration of venetoclax. * Participants who are currently receiving another investigational drug (GO is not considered investigational in this study). * Participants with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known congenital bone marrow failure syndrome. * Participants with known prior allergy to any of the medications used in protocol therapy. * Participants with documented active, uncontrolled infection at the time of study entry. * No known human immunodeficiency virus (HIV) infection. * Post menarchal female participants with positive pregnancy test. * Concomitant Medications * Participants who have received strong and moderate CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort within 7 days of the start of study treatment. * Participants who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit within 3 days of the start of study treatment. * Participants who have hypersensitivity to the active substance or to any of the excipients listed in summary of product characteristics (SPC). * Pregnancy or Breast-Feeding: * Participants who are pregnant or breast-feeding. * Participants of reproductive potential may not participate unless they have agreed to use a highly effective contraceptive method per clinical trials facilitation group (CTFG) guidelines for the duration of study therapy and for 6 months after the completion of all study therapy. * Male participants must use a condom during intercourse and agree not to father a child or donate sperm during therapy and for the duration of study therapy and for 4 months after the completion of all study therapy. Additional criteria to receive a gemtuzumab ozogamicin infusion: Gemtuzumab ozogamicin should not be given: * to participants with history of veno-occlusive disease (VOD)/Sinusoidal obstruction syndrome (SOS) grade 4 * to participants with history of VOD/SOS grade 3 * to participants with CD33 negative leukemic blasts (determined at local lab) Note that these participants are eligible for the study but will not be treated with gemtuzumab ozogamicin.
• Second relapse, who are sufficiently fit to undergo another round of intensive chemotherapy
• First relapse who per investigator discretion cannot tolerate additional anthracycline containing chemotherapy. * Participants must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2 (≥ 50% Lansky or Karnofsky score) * Participants must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to start of protocol treatment:
• Cytotoxic chemotherapy: Must not have received cytotoxic chemotherapy within 14 days prior to start of protocol treatment, except for corticosteroids, low dose cytarabine or hydroxyurea that can be given up to 24 hours prior to start of protocol treatment.
• Intrathecal cytotoxic therapy: No wash-out time is required for participants having received any combination of intrathecal cytarabine, methotrexate, and/or hydrocortisone.
• Antibodies: ≥ 21 days must have elapsed from infusion of last dose of an antibody-drug conjugate before start of protocol treatment. For unmodified antibodies or T cell engaging antibodies, 2 half-lives must have elapsed before start of protocol treatment. Any toxicity related to prior antibody therapy must be recovered to Grade ≤ 1.
• Interleukins, Interferons and Cytokines (other than Hematopoietic Growth Factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than Hematopoietic Growth Factors) before start of protocol treatment.
• Hematopoietic growth factors: ≥ 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or ≥7 days for short-acting growth factor before start of protocol treatment.
• Radiation therapy (RT) (before start of protocol treatment): * ≥ 14 days have elapsed for local palliative RT (small port); * ≥ 84 days must have elapsed if prior craniospinal RT or if ≥ 50% radiation of pelvis; * ≥ 42 days must have elapsed if other substantial bone marrow (BM) radiation.
• Stem Cell Infusions (before start of protocol treatment): * ≥ 84 days since allogeneic (non-autologous) bone marrow or stem cell transplant (with or without total body irradiation \[TBI\]) or boost infusion (any stem cell product; not including donor lymphocyte infusion \[DLI\]) * No evidence of active graft versus host disease (GVHD).
• Participants who are receiving cyclosporine, tacrolimus or other agents to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial. Participants must be off medications to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant for at least 14 days prior to enrollment.
• Cellular Therapy: ≥ 42 days after the completion of donor lymphocyte infusion (DLI) or any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.) before start of protocol treatment.
• Participants with prior exposure to venetoclax are eligible in this trial * Adequate organ function:
• Adequate Renal Function defined as: * Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 60ml/min/1.73 m\^2, or * Normal serum creatinine based on age/sex
• Adequate Liver Function defined as: * Direct bilirubin \< 1.5 x upper limit of normal (ULN), and * Alkaline phosphatase ≤ 2.5 x ULN, and * Serum glutamic pyruvic transaminase (SGPT) alanine aminotransferase (ALT) ≤ 2.5 x ULN. If liver abnormality is due to radiographically identifiable leukemia infiltrate, the participant will remain eligible.
• Cardiac performance: Minimum cardiac function defined as: * No history of congestive heart failure in need of medical treatment * No pre-treatment diminished left ventricular function on echocardiography (shortening fraction \[SF\] \< 25% or ejection fraction \[EF\] \< 40%) * No signs of congestive heart failure at presentation of relapse. * Participant, parent or guardian must sign and date informed consent and pediatric assent (when required), prior to the initiation of screening or study specific procedures, according to local law and legislation. Exclusion Criteria * Participants who in the opinion of the investigator may not be able to comply with the study requirements of the study, are not eligible. * Participants with Down syndrome. * Participants with Acute promyelocytic leukemia (APL) or Juvenile myelomonocytic leukemia (JMML). * Participants with isolated CNS3 disease or symptomatic CNS3 disease. * Participants with malabsorption syndrome or any other condition that precludes enteral administration of venetoclax. * Participants who are currently receiving another investigational drug (GO is not considered investigational in this study). * Participants with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known congenital bone marrow failure syndrome. * Participants with known prior allergy to any of the medications used in protocol therapy. * Participants with documented active, uncontrolled infection at the time of study entry. * No known human immunodeficiency virus (HIV) infection. * Post menarchal female participants with positive pregnancy test. * Concomitant Medications * Participants who have received strong and moderate CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort within 7 days of the start of study treatment. * Participants who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit within 3 days of the start of study treatment. * Participants who have hypersensitivity to the active substance or to any of the excipients listed in summary of product characteristics (SPC). * Pregnancy or Breast-Feeding: * Participants who are pregnant or breast-feeding. * Participants of reproductive potential may not participate unless they have agreed to use a highly effective contraceptive method per clinical trials facilitation group (CTFG) guidelines for the duration of study therapy and for 6 months after the completion of all study therapy. * Male participants must use a condom during intercourse and agree not to father a child or donate sperm during therapy and for the duration of study therapy and for 4 months after the completion of all study therapy. Additional criteria to receive a gemtuzumab ozogamicin infusion: Gemtuzumab ozogamicin should not be given: * to participants with history of veno-occlusive disease (VOD)/Sinusoidal obstruction syndrome (SOS) grade 4 * to participants with history of VOD/SOS grade 3 * to participants with CD33 negative leukemic blasts (determined at local lab) Note that these participants are eligible for the study but will not be treated with gemtuzumab ozogamicin.
DRUG: Fludarabine, DRUG: Cytarabine, DRUG: Gemtuzumab Ozogamicin, DRUG: Azacitidine, DRUG: Venetoclax
Acute Myeloid Leukemia, Leukemia, Not Otherwise Specified, Leukemia, Other
Venetoclax, Gemtuzumab Ozogamicin, Fludarabine, Cytarabine, Relapsed refractory, Azacitidine
Children’s Health
Caloric Restriction and Activity to Reduce Chemoresistance in B-ALL (IDEAL2)
This study is for older children, adolescents, and young adults with B-cell Acute Lymphoblastic Leukemia (B-ALL). Higher amounts of body fat is associated with resistance to chemotherapy in patients with B-ALL. Chemotherapy during the first month causes large gains in body fat in most people, even those who start chemotherapy at a healthy weight. This study is being done to find out if caloric restriction achieved by a personalized nutritional menu and exercise plan during routine chemotherapy can make the patient's ALL more sensitive to chemotherapy and also reduce the amount of body fat gained during treatment. The goals of this study are to help make chemotherapy more effective in treating the patient's leukemia as demonstrated by fewer patients with leukemia minimal residual disease (MRD) while also trying to reduce the amount of body fat that chemotherapy causes the patient to gain in the first month.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
All
10 Years to 25 Years old
Phase 2
NCT05082519
STU-2022-0479
Inclusion Criteria:
• Patients must be ≥ 10.0 and <26.0 years of age.
• Patients must have a diagnosis of de novo B-ALL
• Patients must have a M3 marrow (>25% blasts by morphology) or at least 1,000/µL circulating leukemia cells in PB confirmed by Flow Cytometry (or other convincing evidence of a B-ALL diagnosis not meeting above criteria following central review by the Study Hematopathologist and Study Chair or Vice-Chair).
• The treatment regimen must be the first treatment attempt for B-ALL-
• Must be a multi-agent induction regimen inclusive of vincristine, glucocorticoid, pegaspargase/calaspargase, and daunorubicin or doxorubicin and with a planned duration <35 days.
• Organ function must meet that required for initiation of chemotherapy
• Patients at diagnosis must meet Karnofsky > 50% for patients > 16 years of age and Lansky > 50% for patients ≤ 16 years of age (or be expected to recover prior to Day 8) .
• If the patient is a female of childbearing potential, a negative urine or serum pregnancy test is required within two weeks prior to enrollment.
Exclusion Criteria:
• Patient will be excluded if they are underweight at time of enrollment (BMI% <5th percentile for age for patients age 10-19 years, BMI <18.5 in patients 20-29 years).
• Patients with Down syndrome or a DNA fragility syndrome (such as Fanconi anemia, Bloom syndrome) will be excluded.
• Patient receiving a SJCRH-style "Total Therapy" regimen will be excluded.
• Patients receiving anti-CD20 monoclonal antibody therapy during induction therapy.
• Patients will be excluded if they received treatment for a previous malignancy.
• Patient will be excluded if they are pregnant.
• Patient will be excluded if they have a pre-diagnosis requirement for enteral or parenteral supplementation .
• Patient will be excluded due to inability to perform the intervention (e.g., specific nutritional needs, severe developmental delay, paraplegia)
• Patients will be excluded if they have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results
Behavioral: IDEAL2 Intervention
B-cell Acute Lymphoblastic Leukemia, Obesity, Lymphoid Leukemia
obesity, leukemia, B-cell leukemia, Pediatric obesity, Pediatric ALL
Children’s Health
Study of ONO-4685 in Patients With Relapsed or Refractory T Cell Lymphoma
This study will investigate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ONO-4685 in patients with relapsed or refractory T cell Lymphoma
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Praveen Ramakrishnan Geethakumari
ALL
18 Years and over
PHASE1
NCT05079282
STU-2022-0424
Inclusion Criteria
• Patients aged ≥ 18 years at time of screening
• Written informed consent by the patient or the patients' legally authorized representative prior to screening
• Patients with histologically or cytologically confirmed diagnosis of one of the following subtypes of T-cell lymphoma:
• Peripheral T-cell lymphoma (PTCL): Angioimmunoblastic T-cell lymphoma (AITL), PTCL, not otherwise specified (PTCL-NOS), nodal PTCL with T-follicular helper (TFH) and follicular T-cell lymphoma (FTCL)
• Cutaneous T-cell lymphoma (CTCL) (stages II-B, III, and IV): Mycosis fungoides (MF) and Sezary syndrome (SS)
• Patients must have received at least 2 prior systemic therapies
• Patients with PTCL must have at least 1 measurable lesion (Cheson BD, 2014)
• Patients with CTCL must have assessable disease by response criteria for CTCL (Olsen EA, 2011)
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) = 0-2
• Life expectancy of at least 3 months
• Adequate bone marrow, renal and hepatic functions
• Patients with central nervous system (CNS) involvement
• Patients with Adult T-cell leukemia/lymphoma (ATLL)
• Prior allogeneic stem cell transplant
• Prior treatment with ONO-4685, anti-PD-1, anti-PD-L1, anticytotoxic T lymphocyte associated protein 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
• Prior allogeneic and autologous chimeric antigen receptor (CAR) T-cell therapy
• Patients with malignancies (other than T-cell lymphoma) except for completely resected basal cell carcinoma, stage I squamous cell carcinoma, carcinoma in situ, or any other malignancies that has not relapsed for at least 2 years
• History of severe allergy or hypersensitivity to any monoclonal antibodies, other therapeutic proteins or corticosteroid (e.g., dexamethasone)
• History of infection with Mycobacterium tuberculosis within 2 years prior to the first dose of study treatment
• Patients with systemic and active infection including human immunodeficiency virus (HIV), hepatitis B or C virus infection
• Patients not recovered to Grade 1 or stabilized from the adverse effects (excluding alopecia) of any prior therapy for their malignancies
• Women who are pregnant or lactating
• Patients aged ≥ 18 years at time of screening
• Written informed consent by the patient or the patients' legally authorized representative prior to screening
• Patients with histologically or cytologically confirmed diagnosis of one of the following subtypes of T-cell lymphoma:
• Peripheral T-cell lymphoma (PTCL): Angioimmunoblastic T-cell lymphoma (AITL), PTCL, not otherwise specified (PTCL-NOS), nodal PTCL with T-follicular helper (TFH) and follicular T-cell lymphoma (FTCL)
• Cutaneous T-cell lymphoma (CTCL) (stages II-B, III, and IV): Mycosis fungoides (MF) and Sezary syndrome (SS)
• Patients must have received at least 2 prior systemic therapies
• Patients with PTCL must have at least 1 measurable lesion (Cheson BD, 2014)
• Patients with CTCL must have assessable disease by response criteria for CTCL (Olsen EA, 2011)
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) = 0-2
• Life expectancy of at least 3 months
• Adequate bone marrow, renal and hepatic functions
Exclusion Criteria:
• Patients with central nervous system (CNS) involvement
• Patients with Adult T-cell leukemia/lymphoma (ATLL)
• Prior allogeneic stem cell transplant
• Prior treatment with ONO-4685, anti-PD-1, anti-PD-L1, anticytotoxic T lymphocyte associated protein 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
• Prior allogeneic and autologous chimeric antigen receptor (CAR) T-cell therapy
• Patients with malignancies (other than T-cell lymphoma) except for completely resected basal cell carcinoma, stage I squamous cell carcinoma, carcinoma in situ, or any other malignancies that has not relapsed for at least 2 years
• History of severe allergy or hypersensitivity to any monoclonal antibodies, other therapeutic proteins or corticosteroid (e.g., dexamethasone)
• History of infection with Mycobacterium tuberculosis within 2 years prior to the first dose of study treatment
• Patients with systemic and active infection including human immunodeficiency virus (HIV), hepatitis B or C virus infection
• Patients not recovered to Grade 1 or stabilized from the adverse effects (excluding alopecia) of any prior therapy for their malignancies
• Women who are pregnant or lactating
DRUG: ONO-4685
Relapsed or Refractory T Cell Lymphoma, Lymphoid Leukemia
ONO-4685, PD-1, CD3, Bispecific antibody, PTCL, AITL, PTCL-NOS, nodal PTCL with TFH, FTCL, CTCL, MF, SS
UT Southwestern
Olanzapine Versus Megestrol Acetate for the Treatment of Loss of Appetite Among Advanced Cancer Patients
This phase III trial compares the effects of olanzapine versus megestrol acetate in treating loss of appetite in patients with cancer that has spread to other places in the body (advanced). Olanzapine may stimulate and increase appetite. This study aims to find out if olanzapine is better than the usual approach (megestrol acetate) for stimulating appetite and preventing weight loss.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Namrata Peswani
ALL
18 Years and over
PHASE3
NCT04939090
STU-2021-1170
Inclusion Criteria:
* Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial. Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives or double barrier method (diaphragm plus condom)
* Diagnosis of advanced cancer
* Patient-reported 2-month weight loss of at least 5 pounds (2.3 kilograms) and/or physician-estimated caloric intake of less than 20 calories/kilogram of body weight per day
* The patient must perceive loss of appetite and/or weight as a problem; and have an appetite score of 4 or worse on the "Please rate your appetite...." question that requires a patient response on a 0-10 numeric rating scale
* Not receiving ongoing tube feedings or parenteral nutrition at the time of registration
* Not currently using systemic adrenal steroids (with the exception of short-term dexamethasone within 3 days of chemotherapy for control of chemotherapy side effects)
* No use of androgens, progesterone analogs, or other appetite stimulants within the past month
* Patient should not have poorly controlled hypertension or congestive heart failure at registration
* Patient should not have an obstruction of the alimentary canal, malabsorption, or intractable vomiting (defined as vomiting more than 3 times per day over the preceding week)
* Not currently using olanzapine for another medical condition or had previously used olanzapine for chronic nausea or for any pre-existing psychotic disorder
* Patient should not have had a previous blood clot at any time in the past
* No history of poorly controlled diabetes
* No symptomatic leptomeningeal disease or known brain metastases as these patients may have difficulty taking oral medications
* No history of hypersensitivity to olanzapine or megestrol acetate
* No COVID-19 infection in the past that, in the opinion of the treating physician, had left patients with compromised taste, which has not resolved at the time of registration
* Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test done =\< 14 days prior to registration is required
* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
* Estimated life expectancy of 3 months or longer
* Serum creatinine =\< 2.0 mg/dL
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =\< 3 x upper limit of normal (ULN)
* Fasting glucose \< 140 mg/dL
* Granulocytes \> 1000/hpf
* No treatment with another antipsychotic agent, such as risperidone, quetiapine, clozapine, butyrophenone within 30 days of enrollment
* In order to complete the mandatory patient-completed measures, participants must be able to speak and/or read English or Spanish. Sites seeking to enroll Spanish-speaking patients should have access to Spanish speaking staff on site or through the use of a translation service to be able to conduct the informed consent discussion in Spanish, and to conduct the weekly phone calls
Exclusion Criteria:
* Psychiatric illness which would prevent the patient from giving informed consent
* Medical condition such as uncontrolled infection (including human immunodeficiency virus \[HIV\]), uncontrolled diabetes mellitus or cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
* Patients who cannot swallow oral formulations of the agents
* Patients with impaired decision-making capacity (such as with a diagnosis of dementia or memory loss) are not eligible for this study
* No presence of a hormone-sensitive tumor, such as breast, endometrial, or prostate cancer (this exclusion criterion is intended to circumvent any confounding antineoplastic effects of megestrol acetate) DRUG: Olanzapine, DRUG: Megestrol Acetate, OTHER: Questionnaire Administration
Advanced Malignant Solid Neoplasm, Anorexia, Hematopoietic and Lymphoid Cell Neoplasm, Anklylosing Spondylitis, Anus, Bones and Joints, Brain and Nervous System, Breast - Female, Breast - Male, Carcinoid Tumor, Cardiovascular, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Eye and Orbit, Gall Bladder, Head and Neck, Heart, Hodgkins Lymphoma, Ill - Defined Sites, Kaposis sarcoma, Kidney, Larynx, Leukemia, Not Otherwise Specified, Leukemia, Other, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Lymphoid Leukemia, Lymphoma, Melanoma, skin, Multiple Myeloma, Mycosis Fungoides, Myeloid and Monocytic Leukemia, Non-Hodgkins Lymphoma, Nose, Other, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Hematopoietic, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Psychiatric Disorders, Rectum, Sarcoma, Small Intestine, Soft Tissue, Stomach, Throat, Thyroid, Unknown Sites, Urinary Bladder, Uterine (Endometrial), Vulva
UT Southwestern
Efficacy and Safety of Nemtabrutinib (MK-1026) in Participants With Hematologic Malignancies (MK-1026-003)
The purpose of this study is to evaluate the safety and efficacy of nemtabrutinib (formerly ARQ 531) in participants with hematologic malignancies of chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), Richter's transformation, marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and Waldenström's macroglobulinemia (WM).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Farrukh Awan
ALL
18 Years and over
PHASE2
NCT04728893
STU-2023-0815
Inclusion Criteria:
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7 days prior to allocation
* Has a life expectancy of at least 3 months, based on the investigator assessment
* Has the ability to swallow and retain oral medication
* Participants who are Hepatitis B surface antigen (HBsAg)-positive are eligible if they have received Hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization
* Participants with history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
* Has adequate organ function
* Male participants agree to refrain from donating sperm and agree to either remain abstinent from penile-vaginal intercourse as their preferred and usual lifestyle OR agree to use contraception, during the intervention period and for at least the time required to eliminate the study intervention after last dose of study intervention
* Female participants assigned female sex at birth who are not pregnant or breastfeeding are eligible to participate if not a participant of childbearing potential (POCBP), or if a POCBP they either use a contraceptive method that is highly effective OR remain abstinent from penile-vaginal intercourse as their preferred and usual lifestyle during the intervention period and for at least to eliminate study intervention after the last dose of study intervention
* Participants with HIV are eligible if they meet all of the following: the CD4 count is \>350 cells/uL at screening, the HIV viral load is below the detectable level, are on a stable ART regimen for at least 4 weeks prior to study entry, and are compliant with their ART
Part 1 and Part 2 (Cohorts A to C and J)
* Has a confirmed diagnosis of CLL/SLL with
* At least 2 lines of prior therapy (Part 1 only)
* Part 2 Cohort A: CLL/SLL participants who are relapsed or refractory to prior therapy with a covalent, irreversible Bruton's tyrosine kinase inhibitor (BTKi), and a B-cell lymphoma 2 inhibitor (BCL2i). CLL participants must have received and failed, been intolerant to, or determined by their treating physician to be a poor phosphoinositide 3-kinase inhibitor (PI3Ki) candidate or ineligible for a PI3Ki per local guidelines
* Part 2 Cohort B: CLL/SLL participants who are relapsed or refractory following at least 1 line of prior therapy and are BTKi treatment naive
* Part 2 Cohort C: CLL/SLL participants with 17p deletion or tumor protein p53 (TP53) mutation who are relapsed or refractory following at least 1 line of prior therapy
* Part 2 Cohort J: CLL/SLL participants whose disease relapsed or was refractory to prior therapy with a covalent/irreversible BTKi and BCL2i
* Has active disease for CLL/SLL clearly documented to initiate therapy
* Has evaluable core or excisional lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy or bone marrow aspirate at Screening (optional for participants enrolling in Part 1)
Part 2 (Cohorts D to G)
* Has a confirmed diagnosis of and meets the following prior therapy requirements:
* Participants with Richter's transformation who are relapsed or refractory following at least 1 line of prior therapy (Cohort D)
* Participants with pathologically confirmed MCL, documented by either overexpression of cyclin D1 or t(11;14), who are relapsed or are refractory to chemoimmunotherapy and a covalent irreversible BTKi (Cohort E)
* Participants with MZL (including splenic, nodal, and extra nodal MZL) who are relapsed or refractory to chemoimmunotherapy and a covalent irreversible BTKi (Cohort F)
* Participants with FL who are relapsed or refractory to chemoimmunotherapy, immunomodulatory agents (i.e. lenalidomide plus rituximab) (Cohort G)
* Have measurable disease defined as at least 1 lesion that can be accurately measured in at least 2 dimensions with spiral CT scan
* Has a lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy or bone marrow aspirate (Cohort D) at Screening
Part 2 (Cohort H): confirmed diagnosis of WM; participants who are relapsed or refractory to standard therapies for WM including chemoimmunotherapy and a covalent irreversible BTKi
* Has active disease defined as 1 of the following: systemic symptoms, physical findings, laboratory abnormalities, coexisting disease
* Has measurable disease, satisfying any of the following: at least 1 lesion that can be accurately measured in at least 2 dimensions with spiral CT scan (minimum measurement must be \>15 mm in the longest diameter or \>10 mm in the short axis); IgM ≥450 mg/dL; or bone marrow infiltration of 10%
* Has fresh bone marrow aspirate or a lymph node biopsy for biomarker analysis at Screening or a lymph node biopsy from an archival
Exclusion Criteria:
* Has active HBV/HCV infection (Part 1 and Part 2)
* Has a history of malignancy ≤3 years before providing documented informed consent. Participants with basal cell carcinoma of skin, squamous cell carcinoma of skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potential curative therapy are not excluded. Participants with low-risk, early-stage prostate cancer (T1-T2a, Gleason score ≤6, and prostate-specific antigen \<10 ng/mL) either treated with definitive intent or untreated in active surveillance with SD are not excluded
* Has active central nervous system (CNS) disease
* Has an active infection requiring systemic therapy
* Has received prior systemic anti-cancer therapy within 4 weeks prior to allocation
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
* Has any clinically significant gastrointestinal abnormalities that might alter absorption
* History of severe bleeding disorders DRUG: Nemtabrutinib
Hematologic Malignancies, Waldenstroms Macroglobulinaemia, Non-Hodgkins Lymphoma, Chronic Lymphocytic Leukaemia, Other Hematopoietic
UT Southwestern
The Pediatric Acute Leukemia (PedAL) Screening Trial - A Study to Test Bone Marrow and Blood in Children With Leukemia That Has Come Back After Treatment or Is Difficult to Treat - A Leukemia & Lymphoma Society and Children's Oncology Group Study
This study aims to use clinical and biological characteristics of acute leukemias to screen for patient eligibility for available pediatric leukemia sub-trials. Testing bone marrow and blood from patients with leukemia that has come back after treatment or is difficult to treat may provide information about the patient's leukemia that is important when deciding how to best treat it, and may help doctors find better ways to diagnose and treat leukemia in children, adolescents, and young adults.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kathleen Ludwig
ALL
up to 22 Years old
PHASE1
NCT04726241
STU-2022-0170
Inclusion Criteria:
* Patients must be less than 22 years of age at the time of study enrollment
* Patient must have one of the following at the time of study enrollment:
* Patient has known or suspected relapsed/refractory (including primary refractory) AML as defined in protocol
* This includes isolated myeloid sarcoma
* Patient has known or suspected relapsed/refractory (including primary refractory) myeloid leukemia of Down syndrome (ML-DS)
* Patient has known or suspected relapsed ALL as defined in protocol that meets one of the following criteria:
* Second or greater B-ALL medullary relapse, excluding KMT2Ar
* Any first or greater B-ALL medullary relapse involving KMT2Ar
* Any first or greater T-ALL medullary relapse with or without KMT2Ar
* Patient has known or suspected relapsed/refractory (including primary refractory) mixed phenotype acute leukemia (MPAL) as defined in protocol
* Patient has known or suspected de novo or relapsed/refractory (including primary refractory) treatment-related AML (t-AML)
* Patient has known or suspected de novo or relapsed/refractory (including primary refractory) myelodysplastic syndrome (MDS) or treatment-related myelodysplastic syndrome (t-MDS)
* Note: Relapsed/refractory disease includes stable disease, progressive disease, and disease relapse.
* Patient has known or suspected de novo or relapsed/refractory (including primary refractory) juvenile myelomonocytic leukemia (JMML)
* Note: Relapsed/refractory disease includes stable disease, progressive disease, and disease relapse.
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met PROCEDURE: Biospecimen Collection
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Acute Myeloid Leukemia Post Cytotoxic Therapy, Juvenile Myelomonocytic Leukemia, Mixed Phenotype Acute Leukemia, Myelodysplastic Syndrome, Myelodysplastic Syndrome Post Cytotoxic Therapy, Myeloid Leukemia Associated With Down Syndrome, Leukemia, Other, Myeloid and Monocytic Leukemia
Children’s Health
Safety and Efficacy Study of Epcoritamab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Richter's Syndrome (EPCORE™ CLL-1)
The study is a global, multi-center safety and efficacy trial of epcoritamab, an antibody also known as EPKINLY™ and GEN3013 (DuoBody®-CD3xCD20). Epcoritamab will either be studied as: - Monotherapy, or - Combination therapy: - epcoritamab + venetoclax - epcoritamab + lenalidomide - epcoritamab + R-CHOP (i.e., rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine and prednisone). The study includes patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL)/small lymphocytic lymphoma (SLL) and patients with Richter's Syndrome (RS). Study participants with R/R CLL/SLL are treated either with epcoritamab as monotherapy or epcoritamab + venetoclax. Study participants with RS are treated either with epcoritamab as monotherapy or epcoritamab + lenalidomide or epcoritamab + R-CHOP. The trial consists of two parts, a dose-escalation phase (phase Ib) and an expansion phase (phase II). Patients with RS are only included in the expansion phase.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Farrukh Awan
All
18 Years and over
Phase 1/Phase 2
NCT04623541
STU-2020-1263
Key Inclusion Criteria
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
• Evidence of CD20 positivity in a sample representative of the disease at Screening.
• Acceptable hematology parameters and organ function based on baseline bloodwork.
• For R/R CLL arms - Must have active CLL/SLL disease requiring treatment per iwCLL 2018 criteria.
• For R/R CLL arms - Received at least 2 prior lines of systemic anti-neoplastic therapy including a Bruton's tyrosine kinase (BTK) inhibitor.
• For all RS arms - Have tumor biopsy-proven CD20+ Diffuse large B-cell Lymphoma (DLBCL) and a clinical history of CLL/SLL.
• For all RS arms - Must have measurable disease by fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) or magnetic resonance imaging (MRI) scan.
• For all RS arms - Must provide mandatory formalin-fixed, paraffin-embedded (FFPE) tumor biopsy sample.
• Life expectancy >3 months on standard of care (SOC).
• For RS - monotherapy arm: Deemed as ineligible for chemoimmunotherapy at investigator's discretion or participant who refuses to receive intensive chemotherapy
• For RS - lenalidomide combination therapy arm
• Deemed as ineligible for chemoimmunotherapy at the investigator's discretion, or participant who refuses to receive intensive chemotherapy.
• Eligible for treatment with lenalidomide.
• Must be willing to use contraception and adhere to the Lenalidomide Pregnancy Risk Minimization Plan
• For RS - R-CHOP combination Therapy Arm -
• Eligible for treatment with R-CHOP.
• For R/R CLL - venetoclax combination Therapy arm - after receiving at least 1 prior line of systemic antineoplastic therapy. Key Exclusion Criteria
• Received prior treatment with a CD3×CD20 bispecific antibody.
• Received any prior allogeneic hematopoietic stem cell transplantation (HSCT) or solid organ transplantation.
• Received (CAR) T-cell therapy within 100 days or an investigational drug within 4 weeks, prior to first dose of epcoritamab.
• Autoimmune disease or other diseases that require permanent or high-dose immunosuppressive therapy.
• Received vaccination with live vaccines within 28 days.
• Clinically significant cardiac disease.
• Known current malignancy other than inclusion diagnosis.
• Has had major surgery within 4 weeks.
• Active hepatitis B virus or active hepatitis C.
• Known history of HIV.
• For R/R CLL arms - Any history of RS or evidence indicating a potential Richter's transformation.
• Received venetoclax within 24 months prior to beginning venetoclax ramp-up for this trial and progressed on treatment.
• For all RS arms - Diagnosis of Richter's syndrome not of the DLBCL subtype such as Hodgkin's lymphoma, prolymphocytic leukemia.
• RS - Lenalidomide Combination Therapy and RS Monotherapy Arms - received more than 2 prior lines of therapy for RS. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
• Evidence of CD20 positivity in a sample representative of the disease at Screening.
• Acceptable hematology parameters and organ function based on baseline bloodwork.
• For R/R CLL arms - Must have active CLL/SLL disease requiring treatment per iwCLL 2018 criteria.
• For R/R CLL arms - Received at least 2 prior lines of systemic anti-neoplastic therapy including a Bruton's tyrosine kinase (BTK) inhibitor.
• For all RS arms - Have tumor biopsy-proven CD20+ Diffuse large B-cell Lymphoma (DLBCL) and a clinical history of CLL/SLL.
• For all RS arms - Must have measurable disease by fluorodeoxyglucose-positron emission tomography (FDG-PET) and computed tomography (CT) or magnetic resonance imaging (MRI) scan.
• For all RS arms - Must provide mandatory formalin-fixed, paraffin-embedded (FFPE) tumor biopsy sample.
• Life expectancy >3 months on standard of care (SOC).
• For RS - monotherapy arm: Deemed as ineligible for chemoimmunotherapy at investigator's discretion or participant who refuses to receive intensive chemotherapy
• For RS - lenalidomide combination therapy arm
• Deemed as ineligible for chemoimmunotherapy at the investigator's discretion, or participant who refuses to receive intensive chemotherapy.
• Eligible for treatment with lenalidomide.
• Must be willing to use contraception and adhere to the Lenalidomide Pregnancy Risk Minimization Plan
• For RS - R-CHOP combination Therapy Arm -
• Eligible for treatment with R-CHOP.
• For R/R CLL - venetoclax combination Therapy arm - after receiving at least 1 prior line of systemic antineoplastic therapy. Key Exclusion Criteria
• Received prior treatment with a CD3×CD20 bispecific antibody.
• Received any prior allogeneic hematopoietic stem cell transplantation (HSCT) or solid organ transplantation.
• Received (CAR) T-cell therapy within 100 days or an investigational drug within 4 weeks, prior to first dose of epcoritamab.
• Autoimmune disease or other diseases that require permanent or high-dose immunosuppressive therapy.
• Received vaccination with live vaccines within 28 days.
• Clinically significant cardiac disease.
• Known current malignancy other than inclusion diagnosis.
• Has had major surgery within 4 weeks.
• Active hepatitis B virus or active hepatitis C.
• Known history of HIV.
• For R/R CLL arms - Any history of RS or evidence indicating a potential Richter's transformation.
• Received venetoclax within 24 months prior to beginning venetoclax ramp-up for this trial and progressed on treatment.
• For all RS arms - Diagnosis of Richter's syndrome not of the DLBCL subtype such as Hodgkin's lymphoma, prolymphocytic leukemia.
• RS - Lenalidomide Combination Therapy and RS Monotherapy Arms - received more than 2 prior lines of therapy for RS. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Biological: Epcoritamab, Biological: Epcoritamab, Drug: rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone, Drug: Venetoclax, Biological: Epcoritamab, Drug: Lenalidomide
Relapsed/Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Richter's Syndrome, Lymphoid Leukemia
DuoBody®, Bispecific antibodies, Anti-CD3, Anti-CD20
UT Southwestern
Luspatercept and Lenalidomide (L2) in Lower-risk, Non-del(5q) MDS Patients
The purpose of this study is to evaluate if the combination of drugs, Lenalidomide and Luspatercept, will help improve the treatment of anemia in patients with lower-risk Myelodysplastic Syndrome (MDS).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
ALL
18 Years to old
PHASE1
NCT04539236
STU-2023-1130
Inclusion Criteria:
• Subject is ≥ 18 years of age the time of signing the informed consent form (ICF).
• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
• Documented diagnosis of MDS according to World Health Organization (WHO) / French-American-British (FAB) classification that meets International Prognostic Scoring System Revised (IPSS-R) classification (Greenberg, 2012) of very low, low, or intermediate risk disease; intermediate patients must have a blast percentage \<5% to be enrolled.
• Subjects can be ESA-naïve, or refractory or intolerant to, or ineligible for, prior ESA treatment, as defined by any one of the following: * Refractory to prior ESA treatment - documentation of non-response or response that is no longer maintained to prior ESA-containing regimen, either as single agent or combination (eg, with G-CSF); ESA regimen must have been either: * recombinant human erythropoietin (rHu EPO) ≥ 40,000 IU/wk for at least 8 doses or equivalent; OR * darbepoetin alpha ≥ 200-500 μg Q1-3W for at least 4 doses or equivalent; * Intolerant to prior ESA treatment - documentation of discontinuation of prior ESAcontaining regimen, either as single agent or combination (eg, with G-CSF), at any time after introduction due to intolerance or an adverse event * ESA ineligible - Low chance of response to ESA based on endogenous serum erythropoietin level \> 200 U/L for subjects not previously treated with ESAs
• If previously treated with ESAs, agents must have been discontinued ≥ 4 weeks prior to date of C1D1.
• Requires RBC transfusions, as documented by the following criteria: * average transfusion requirement of ≥ 2 units/8 weeks of packed Red Blood Cells (pRBC)s preceding C1D1. * Hemoglobin levels at the time of or within 7 days prior to administration of a RBC transfusion must have been ≤ 10.0 g/dL for the transfusion to be counted towards meeting eligibility criteria. Red blood cell transfusions administered when Hgb levels were \> 10.0 g/dL and/or RBC transfusions administered for elective surgery will not qualify as a required transfusion for the purpose of meeting eligibility criteria.
• Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 (Appendix 1)
• Females of childbearing potential (FCBP), defined as a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months), must: * Have two negative pregnancy tests (urine or serum) as verified by the Investigator prior to starting study therapy (unless the screening pregnancy test was done within 72 hours of C1D1). She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. * If sexually active, agree to use, and be able to comply with, highly effective contraception without interruption, 5 weeks prior to starting investigational product, during the study therapy (including dose interruptions), and for 12 weeks after discontinuation of study therapy.
• Male subjects must: * Agree to use a condom, defined as a male latex condom or nonlatex condom NOT made out of natural (animal) membrane (for example, polyurethane), during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 12 weeks following investigational product discontinuation, even if he has undergone a successful vasectomy.
• Subject must have a negative Coronavirus Disease of 2019 (COVID-19) test completed ≤7 days prior to administration of protocol therapy.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
Exclusion Criteria:
• Prior therapy with Lenalidomide.
• Previously treated with either luspatercept (ACE-536) or sotatercept (ACE-011)
• MDS associated with del 5q cytogenetic abnormality
• Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding * iron deficiency to be determined by serum ferritin ≤ 15 μg/L and additional testing if clinically indicated (eg, calculated transferrin saturation \[iron/total iron binding capacity ≤ 20%\] or bone marrow aspirate stain for iron).
• Prior allogeneic stem cell transplant
• Known history of diagnosis of AML
• Use of any of the following within 4 weeks prior to C1D1: * anticancer cytotoxic chemotherapeutic agent or treatment * other RBC hematopoietic growth factors (eg, Interleukin-3) * investigational drug or device, or approved therapy for investigational use. If the half-life of the previous investigational product is known, use within 5 times the half-life prior to C1D1 or within 5 weeks, whichever is longer is excluded.
• Uncontrolled hypertension, defined as repeated elevations of diastolic blood pressure (DBP) ≥ 100 mmHg despite adequate treatment.
• Prior history of malignancies, other than MDS, unless the subject has been free of the disease (including completion of any active or adjuvant treatment for prior malignancy) for ≥ 1 year. However, subjects with the following history/concurrent conditions involving in situ cancer (or similar) are allowed: * Basal or squamous cell carcinoma of the skin * Carcinoma in situ of the cervix * Carcinoma in situ of the breast * Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis (TNM) clinical staging system)
• Major surgery within 4 weeks prior to C1D1. Subjects must have completely recovered from any previous surgery prior to C1D1
• History of stroke, deep venous thrombosis (DVT), pulmonary or arterial embolism within 6 months prior to C1D1
• Pregnant or breastfeeding females
• Subject has any significant medical condition, laboratory abnormality, psychiatric illness, or is considered vulnerable by local regulations (eg, imprisoned or institutionalized) that, in the opinion of the Investigator, would prevent the subject from participating in the study.
DRUG: Lenalidomide, DRUG: Luspatercept
Myelodysplastic Syndromes, Myeloid and Monocytic Leukemia
non-del(5q) MDS
UT Southwestern
Testing the Use of Steroids and Tyrosine Kinase Inhibitors With Blinatumomab or Chemotherapy for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia in Adults
This phase III trial compares the effect of usual treatment of chemotherapy and steroids and a tyrosine kinase inhibitor (TKI) to the same treatment plus blinatumomab. Blinatumomab is a Bi-specific T-Cell Engager ('BiTE') that may interfere with the ability of cancer cells to grow and spread. The information gained from this study may help researchers determine if combination therapy with steroids, TKIs, and blinatumomab work better than the standard of care.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
ALL
18 Years to 75 Years old
PHASE3
NCT04530565
STU-2021-0640
Inclusion Criteria:
* ELIGIBILITY CRITERIA FOR PRE-REGISTRATION (TO STEP 0)
* Patient must be \>= 18 and =\< 75 years of age
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status between 0-3
* Patient must be newly diagnosed with B acute lymphoblastic leukemia (B-ALL) or is suspected to have acute lymphoblastic leukemia (ALL)
* Patient must have BCR-ABL1 positive disease. The diagnosis of ALL and the presence of BCR-ABL translocation must be confirmed centrally. Patients can be registered and begin step 1 therapy while awaiting central laboratory eligibility confirmation
* NOTE: Bone marrow aspirate and/or peripheral blood specimen must be submitted to the ECOG-American College of Radiology Imaging Network (ACRIN) Leukemia Laboratory at MD Anderson Cancer Center to determine patient's eligibility for registration to Step 1 or confirm patient evaluability. Centrally fluorescence-activated cell sorting (FACS) analysis will be performed to determine B-ALL and to exclude acute myeloid leukemia (AML) or acute bi-phenotypic leukemia and baseline BCR-ABL status will be determined by fluorescent in situ hybridization (FISH). The ECOG-ACRIN Leukemia Laboratory will forward results within 48 hours of receipt of the specimen to the submitting institution. Bone marrow aspirate is to be from first pull (initial or re-direct). Specimens must contain sufficient blast cells. In cases where the bone marrow aspiration may be inadequate, or the bone marrow examination has already been performed prior to study consent and enrollment on Step 0, peripheral blood may be submitted, with recommendation that adequate circulating blasts are present (\> 10%). If a diagnosis of BCR-ABL positive B-ALL has already been established by local Clinical Laboratory Improvement Act (CLIA) certified laboratories, the patient may be registered to step 1 without waiting for central confirmation
* Patient must not have a diagnosis of BCR/ABL T-ALL
* Patient must not have received chemotherapy for B-ALL. Patients who received up to five days of therapy (hydroxyurea and/or steroids of any kind) with the aim to reduce disease burden prior to study registration to Step 1 are eligible
* Patient must not have unstable epilepsy that requires treatment
* Patients with lymphoid blast crisis chronic myeloid leukemia (CML) are not eligible
* ELIGIBILITY CRITERIA FOR REGISTRATION TO STEP 1
* Patient must have a diagnosis of Philadelphia chromosome positive (Ph+) ALL that has been determined locally and bone marrow and/or peripheral blood was sent and receipt confirmed for central confirmation or determined centrally by the ECOG-ACRIN Leukemia Laboratory at MD Anderson Cancer Center
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy. A patient of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patients must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse from the time of step 1 registration, while on study treatment, and until at least six months after the last dose of study treatment
* Total bilirubin =\< 3 mg/dL (patients with Gilbert's syndrome must have a total bilirubin =\< 5 mg/dL) (obtained =\< 28 days prior to step 1 registration)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X the institutional upper limit of normal (ULN) (obtained =\< 28 days prior to step 1 registration)
* Estimated creatinine clearance \> 45 mL/min (based on Cockcroft-Gault equation) (obtained =\< 28 days prior to step 1 registration)
* Patients with acute organ dysfunction at step 1 registration, which may be attributed to leukemia can be registered regardless of lab results at presentation. Such patients will be allowed to register and can start Arm A steroid + TKI therapy but will only be allowed to proceed to step 2 randomization if the eligibility criteria outlined is met
* Patients who presented with no evidence of acute organ dysfunction but during step 0 experienced a rise in liver enzymes which investigator suspects to be a side effect of any of prescribed drugs, are allowed to be registered regardless of the level of liver enzymes. Step 2 randomization must be withheld until the eligibility criteria outline is met but no more than 14 days after concluding Arm A therapy
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable or on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have an undetectable HCV viral load and if indicated, on treatment
* Patients with a prior malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patient must not have active concomitant malignancy. Patients on chronic hormonal therapy for breast or prostate cancer or patients treated with maintenance with targeted agents but are in remission with no evidence for the primary malignancies are eligible
* Patient must not have complaints of symptoms and/or have clinical and/or radiological signs that indicate an uncontrolled infection or any other concurrent medical condition that could be exacerbated by the treatment or would seriously complicate compliance with the protocol
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients must be class 2B or better
* Investigators must confirm which TKI patient is to receive
* NOTE: Patients with known T315I mutation status should receive ponatinib treatment
* NOTE: In situations due to insurance coverage issues and the pre-selected TKI is not immediately available, patients can receive dasatinib or imatinib during step 1. The investigator must re-specify dasatinib or ponatinib prior to step 2 randomization and from then on patients must receive the pre-selected TKI only
* ELIGIBILITY CRITERIA FOR RANDOMIZATION TO STEP 2
* Patient must have completed at least 7 and no more than 21 days of protocol-treatment on Arm A prior to step 2 randomization. (Days in which arm A therapy was withheld for any reason are not counted)
* NOTE: First day of steroids prescription after registration will be considered as the first day of study therapy. The selected TKI must be initiated prior to randomization
* Patients who presented with acute organ dysfunction within 2 weeks of registration to step 1 must have total bilirubin =\< 2 X institutional upper limit of normal (ULN)
* AST(SGOT) and ALT(SGPT) =\< 2 X the institutional upper limit of normal (ULN)
* Estimated creatinine clearance \> 45 mL/min (based on Cockcroft-Gault equation)
* Investigators must confirm which TKI patient is to receive.
* NOTE: Patients with known T315I mutation status should receive ponatinib treatment
* For patients under age 70, intended chemotherapy regimen must have been determined prior to randomization
* Patient must not have active central nervous system (CNS) involvement by leukemic blasts. Patients with signs of CNS involvement at presentation are eligible for randomization if clearance of blasts from the cerebrospinal fluid (CSF) is demonstrated
* Patients must have resolved any serious infectious complications related to therapy
* Any significant medical complications related to therapy must have resolved
* ELIGIBILITY CRITERIA FOR REGISTRATION TO STEP 3 (RE-INDUCTION)
* Institution has received centralized MRD results confirming positive status
* Patients who presented with acute organ dysfunction within 2 weeks of registration to step 1 must have total bilirubin =\< 2 X institutional ULN
* Patients who presented with acute organ dysfunction must have AST (SGOT)/ALT (SGPT) =\< 2 X institutional upper limit of normal (ULN)
* Patients who presented with acute organ dysfunction must have an estimated creatinine clearance \> 45 mL/min (based on Cockcroft-Gault equation)
* Investigators must confirm which TKI patient is to receive
* NOTE: Patients with known T315I mutation status should receive ponatinib treatment
* For patients under age 70 and previously assigned to Arm C, intended chemotherapy regimen must have been determined
* Step 3 (Re-Induction): Patients must have resolved any serious infectious complications related to therapy
* Step 3 (Re-Induction): Any significant medical complications related to therapy must have resolved PROCEDURE: Biospecimen Collection, BIOLOGICAL: Blinatumomab, PROCEDURE: Bone Marrow Aspiration and Biopsy, DRUG: Cyclophosphamide, DRUG: Cytarabine, DRUG: Dasatinib, DRUG: Dexamethasone, DRUG: Doxorubicin Hydrochloride, PROCEDURE: Echocardiography Test, PROCEDURE: Electrocardiography, PROCEDURE: Lumbar Puncture, DRUG: Mesna, DRUG: Methotrexate, PROCEDURE: Multigated Acquisition Scan, DRUG: Ponatinib Hydrochloride, DRUG: Prednisone, DRUG: Vincristine Sulfate
B Acute Lymphoblastic Leukemia With t(9,22)(q34.1,q11.2), BCR-ABL1, Leukemia, Other
UT Southwestern
Pemigatinib After Chemotherapy for the Treatment of Newly Diagnosed Acute Myeloid Leukemia
This phase I trial identifies the best dose and clinical benefit of giving pemigatinib following standard induction chemotherapy in patients with newly diagnosed acute myeloid leukemia. Pemigatinib selectively inhibits FGFR (fibroblast growth factor receptor) activity, a receptor that may contribute to the growth of leukemia cells. The genetic changes responsible for activating the growth of leukemia cells can be unique to each patient and can change during the course of the disease. Chemotherapy drugs, such as cytarabine and daunorubicin work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
ALL
18 Years to old
PHASE1
NCT04659616
STU-2023-0606
Inclusion Criteria:
* PRE-SCREENING INCLUSION CRITERIA: Ability to understand and the willingness to sign a written informed consent document
* PRE-SCREENING INCLUSION CRITERIA: Age \>= 18 years at time of informed consent. Both men and women of all races and ethnic groups will be included
* PRE-SCREENING INCLUSION CRITERIA: Participants must consent to a bone marrow aspirate/biopsy that will be collected prior to start of planned 7+3 induction therapy. Patients with known favorable risk AML (2022 European Leukemia Net \[ELN\] Guidelines) or FLT3 mutations should not be pre-screened. If the risk category is unknown, then it is okay to pre-screen patients for study. Adverse or intermediate risk needs to be confirmed prior to treatment with pemigatinib (during screening period) as outlined below
* TREATMENT INCLUSION CRITERIA: Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* TREATMENT INCLUSION CRITERIA: For both the dose-determining and dose-expansion cohort, study population is limited to: Newly diagnosed, morphologically documented AML, based on the World Health Organization (WHO) 2008 classification, with wild-type FLT3 and cytogenetics or mutations associated with intermediate or adverse prognostic risk per European Leukemia Net (ELN) guidelines. These include:
* t(9;11)(p21.3;q23.3); MLLT3-KMT2A
* Cytogenetic abnormalities not classified as favorable
* t(6;9)(p23;q34.1); DEK-NUP214
* t(v;11q23.3); KMT2A rearranged
* t(9;22)(q34.1;q11.2); BCR-ABL1
* inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2,MECOM(EVI1)
* -5 or del(5q); -7; -17/abn(17p)
* Complex karyotype - defined as three or more unrelated chromosome abnormalities in the absence of 1 of the WHO-designated recurring translocations or inversions, that is, t(8;21), inv(16) or t(16;16), t(9;11), t(v;11)(v;q23.3), t(6;9), inv(3) or t(3;3); AML with BCR-ABL1
* Monosomal karyotype - defined by the presence of 1 single monosomy (excluding loss of X or Y) in association with at least 1 additional monosomy or structural chromosome abnormality (excluding core-binding factor AML)
* Mutated RUNX1 (without favorable risk cytogenetics/mutations)
* Mutated BCOR (without favorable risk cytogenetics/mutations)
* Mutated EZH2 (without favorable risk cytogenetics/mutations)
* Mutated ASXL1 (without favorable risk cytogenetics/mutations)
* Mutated SF3B1 (without favorable risk cytogenetics/mutations)
* Mutated SRSF2 (without favorable risk cytogenetics/mutations)
* Mutated STAG2 (without favorable risk cytogenetics/mutations)
* Mutated U2AF1, (without favorable risk cytogenetics/mutations)
* Mutated ZRSR2 (without favorable risk cytogenetics/mutations)
* Mutated TP53 (mono- or biallelic) at a variant allele fraction of at least 10%
* TREATMENT INCLUSION CRITERIA: Serum creatinine clearance \>= 30 mL/min (as calculated by Cockcroft-Gault formula) (on or by day 8 of induction therapy, prior to starting pemigatinib)
* TREATMENT INCLUSION CRITERIA: Serum phosphate within institutional upper limit of normal (ULN) or can be corrected with supplementation/ phosphate binders to be within institutional ULN (on or by day 8 of induction therapy, prior to starting pemigatinib)
* TREATMENT INCLUSION CRITERIA: Serum electrolytes within institutional ULN: potassium, calcium (total, or corrected for serum albumin in case of hypoalbuminemia) and magnesium. If outside of normal limits, participant will be eligible when electrolytes are corrected (on or by day 8 of induction therapy, prior to starting pemigatinib)
* TREATMENT INCLUSION CRITERIA: Total serum bilirubin =\< 3 x ULN (on or by day 8 of induction therapy, prior to starting pemigatinib)
* TREATMENT INCLUSION CRITERIA: Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) =\< 3 x ULN (on or by day 8 of induction therapy, prior to starting pemigatinib)
* TREATMENT INCLUSION CRITERIA: Participants must consent to standard of care bone marrow aspirate/biopsies during treatment. Bone marrow biopsies will be obtained prior to study, on day 21 (+/- 3 days, if considered institutional standard of care), after recovery from induction therapy, and at the end of consolidation and/or prior to allogeneic stem cell transplant
* TREATMENT INCLUSION CRITERIA: Female participants of childbearing potential must agree to use effective contraception (2 forms of contraception or abstinence) from the screening visit until 6 months following the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
* TREATMENT INCLUSION CRITERIA: Male patients of childbearing potential having intercourse with females of childbearing potential must agree to abstain from heterosexual intercourse or have their partner use 2 forms of contraception from the screening visit until 3 months following the last dose of study treatment. The male participant must also refrain from sperm donation from the screening visit until 3 months following the last dose of study treatment
Exclusion Criteria:
* PRE-SCREENING EXCLUSION CRITERIA: Diagnosis of acute promyelocytic leukemia (APL, or AML M3 subtype) per WHO classification
* PRE-SCREENING EXCLUSION CRITERIA: AML with FLT3 mutations that qualify for standard of care treatment with 7+3 and midostaurin (e.g. FLT3 ITD or TKD with allelic ratio \> 0.05)
* PRE-SCREENING EXCLUSION CRITERIA: Favorable risk AML: inv(16), t(8;21), NPM1 mutations without FLT3-ITD, or in-frame mutations (mono- or biallelic) affecting the basic leucine zipper region of CEBPA
* PRE-SCREENING EXCLUSION CRITERIA: Any cancer-directed therapy within 2 weeks prior to starting planned 7+3 induction regimen, with the exception of hydroxyurea, which is allowed to control white blood cell count, or empiric all-trans retinoic acid (ATRA) for suspected APL
* PRE-SCREENING EXCLUSION CRITERIA: Prior receipt of a selective FGFR inhibitor
* PRE-SCREENING EXCLUSION CRITERIA: Known liver disease
* PRE-SCREENING EXCLUSION CRITERIA: History of calcium and phosphate hemostasis disorder or systemic mineral imbalance with ectopic calcification of soft tissues
* Except for commonly observed calcifications in soft tissues such as the skin, kidney tendon, or vessels due to injury, disease, or aging in the absence of systemic mineral imbalance)
* PRE-SCREENING EXCLUSION CRITERIA: History of hypovitaminosis D being actively treated with supraphysiologic doses (e.g., 50,000 IU/weekly) to replenish the deficiency. Supraphysiologic doses of vitamin D need to be discontinued prior to starting pemigatinib. Vitamin D supplements are allowed
* PRE-SCREENING EXCLUSION CRITERIA: Untreated human immunodeficiency virus (HIV) or active hepatitis C detectable by PCR, or chronic hepatitis B
* Individuals positive for hepatitis B core antibody who are receiving intravenous immunoglobulin (IVIg) are eligible if HepB PCR is negative
* PRE-SCREENING EXCLUSION CRITERIA: History of cerebrovascular accident or intracranial hemorrhage within 2 months of enrollment
* PRE-SCREENING EXCLUSION CRITERIA: Unwillingness to receive infusion of blood products
* PRE-SCREENING EXCLUSION CRITERIA: Inability to take oral medication
* PRE-SCREENING EXCLUSION CRITERIA: Gastrointestinal condition/disorders that may raise gastric and/or small intestinal pH that could interfere with absorption, metabolism, or excretion of pemigatinib
* PRE-SCREENING EXCLUSION CRITERIA: Known history and/or current evidence of ectopic mineralization/calcification, including (but not limited to): soft tissue, kidneys, intestine, myocardia, or lung, excepting calcified lymph nodes and asymptomatic arterial or cartilage/tendon calcification
* PRE-SCREENING EXCLUSION CRITERIA: Concurrent active malignancy with expected survival of \< 1 year
* PRE-SCREENING EXCLUSION CRITERIA: Active central nervous system involvement with AML
* TREATMENT EXCLUSION CRITERIA: Clinically significant coagulation abnormality (e.g., disseminated intravascular coagulation) that is present on or by day 8 of induction therapy prior to starting pemigatinib
* TREATMENT EXCLUSION CRITERIA: Clinically significant or uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months from day 1 of planned induction therapy, New York Heart Association class III or IV congestive heart failure, and uncontrolled arrhythmia (participants with pacemaker or with atrial fibrillation and well controlled heart rate are allowed). History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful.
* A screening QT interval by Fridericia's Correction Formula (QTcF) interval \> 480 ms will result in exclusion.
* For participants with an intraventricular conduction delay (QRS interval \> 120 ms), the JTc interval may be used in place of the QTc with approval from Sponsor-Investigator. The JTc must be =\< 340 ms if JTc is used in place of the QTc.
* TREATMENT EXCLUSION CRITERIA: Left ventricular ejection fraction (LVEF) by echocardiogram \< 45% prior to initiating pemigatinib
* TREATMENT EXCLUSION CRITERIA: Active infection that is not well-controlled by antibacterial or antiviral therapy
* TREATMENT EXCLUSION CRITERIA: Current use of prohibited medications including use of any potent CYP3A4 inducers within 14 days or five half-lives (whichever is longer) before the first dose of study drug.
* Use of CYP3A4 inhibitors should be avoided but, if medically necessary, is permitted with a dose reduction of study drug
* Use of moderate CYP3A4 inhibitors are permitted.
* Based on the low overall bioavailability of topical ketoconazole, there are no restrictions on topical ketoconazole
* TREATMENT EXCLUSION CRITERIA: Current use of prohibited medication
* TREATMENT EXCLUSION CRITERIA: Hypersensitivity to pemigatinib, or its excipients, when administered alone
* TREATMENT EXCLUSION CRITERIA: Current evidence of corneal disorder/keratopathy, including (but not limited to): bullous/band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivitis, etc., as confirmed by ophthalmologic examination.
* TREATMENT EXCLUSION CRITERIA: Pregnancy or breastfeeding at the time of enrollment
* TREATMENT EXCLUSION CRITERIA: Any concurrent condition that, in the investigator's opinion, would jeopardize the safety of the participant or compliance with the protocol
* TREATMENT EXCLUSION CRITERIA: Active central nervous system involvement with AML
* TREATMENT EXCLUSION CRITERIA: Patients with FLT mutations PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspirate, PROCEDURE: Bone Marrow Biopsy, DRUG: Cytarabine, DRUG: Daunorubicin, PROCEDURE: Electrocardiography, DRUG: Pemigatinib
Acute Myeloid Leukemia, Myeloid and Monocytic Leukemia
UT Southwestern
A Study to Compare Standard Chemotherapy to Therapy With CPX-351 and/or Gilteritinib for Patients With Newly Diagnosed AML With or Without FLT3 Mutations
This phase III trial compares standard chemotherapy to therapy with liposome-encapsulated daunorubicin-cytarabine (CPX-351) and/or gilteritinib for patients with newly diagnosed acute myeloid leukemia with or without FLT3 mutations. Drugs used in chemotherapy, such as daunorubicin, cytarabine, and gemtuzumab ozogamicin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. CPX-351 is made up of daunorubicin and cytarabine and is made in a way that makes the drugs stay in the bone marrow longer and could be less likely to cause heart problems than traditional anthracycline drugs, a common class of chemotherapy drug. Some acute myeloid leukemia patients have an abnormality in the structure of a gene called FLT3. Genes are pieces of DNA (molecules that carry instructions for development, functioning, growth and reproduction) inside each cell that tell the cell what to do and when to grow and divide. FLT3 plays an important role in the normal making of blood cells. This gene can have permanent changes that cause it to function abnormally by making cancer cells grow. Gilteritinib may block the abnormal function of the FLT3 gene that makes cancer cells grow. The overall goals of this study are, 1) to compare the effects, good and/or bad, of CPX-351 with daunorubicin and cytarabine on people with newly diagnosed AML to find out which is better, 2) to study the effects, good and/or bad, of adding gilteritinib to AML therapy for patients with high amounts of FLT3/ITD or other FLT3 mutations and 3) to study changes in heart function during and after treatment for AML. Giving CPX-351 and/or gilteritinib with standard chemotherapy may work better in treating patients with acute myeloid leukemia compared to standard chemotherapy alone.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
ALL
up to 21 Years old
PHASE3
NCT04293562
STU-2020-0830
Inclusion Criteria:
* All patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part A) prior to enrollment and treatment on AAML1831
* Patients must be less than 22 years of age at the time of study enrollment
* Patient must be newly diagnosed with de novo AML according to the 2016 World Health Organization (WHO) classification with or without extramedullary disease
* Patient must have 1 of the following:
* \>= 20% bone marrow blasts (obtained within 14 days prior to enrollment)
* In cases where extensive fibrosis may result in a dry tap, blast count can be obtained from touch imprints or estimated from an adequate bone marrow core biopsy
* \< 20% bone marrow blasts with one or more of the genetic abnormalities associated with childhood/young adult AML as provided in the protocol (sample obtained within 14 days prior to enrollment)
* A complete blood count (CBC) documenting the presence of at least 1,000/uL (i.e., a white blood cell \[WBC\] count \>= 10,000/uL with \>= 10% blasts or a WBC count of \>= 5,000/uL with \>= 20% blasts) circulating leukemic cells (blasts) if a bone marrow aspirate or biopsy cannot be performed (performed within 7 days prior to enrollment)
* ARM C: Patient must be \>= 2 years of age at the time of Late Callback
* ARM C: Patient must have FLT3/ITD allelic ratio \> 0.1 as reported by Molecular Oncology
* ARM C: Patient does not have any congenital long QT syndrome or congenital heart block
* ARM C: Females of reproductive potential must agree to use effective contraception during treatment and for at least 6 months after the last dose of gilteritinib
* ARM C: Lactating women must agree not to breastfeed during treatment with gilteritinib and for 2 months after the last dose of gilteritinib
* ARM C: Males of reproductive potential must agree to use effective contraception during treatment and for at least 4 months after the last dose of gilteritinib
* ARM D: Patient must be \>= 2 years of age at the time of Late Callback
* ARM D: Patient must have one of the clinically relevant non-ITD FLT3 activating mutations as reported by Foundation Medicine
* ARM D: Females of reproductive potential must agree to use effective contraception during treatment and for at least 6 months after the last dose of gilteritinib
* ARM D: Lactating women must agree not to breastfeed during treatment with gilteritinib and for 2 months after the last dose of gilteritinib
* ARM D: Males of reproductive potential must agree to use effective contraception during treatment and for at least 4 months after the last dose of gilteritinib
* NEUROPSYCHOLOGICAL TESTING: Patient must be enrolled on Arm A or Arm B. Patients who transfer to Arm C or Arm D are not eligible
* NEUROPSYCHOLOGICAL TESTING: Patient must be 5 years or older at the time of enrollment
* NEUROPSYCHOLOGICAL TESTING: English-, French- or Spanish-speaking
* NEUROPSYCHOLOGICAL TESTING: No known history of neurodevelopmental disorder prior to diagnosis of AML (e.g., Down syndrome, fragile X, William syndrome, mental retardation)
* NEUROPSYCHOLOGICAL TESTING: No significant visual or motor impairment that would prevent computer use or recognition of visual test stimuli
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
* Fanconi anemia
* Shwachman Diamond syndrome
* Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21
* Telomere disorders
* Germline predispositions known, or suspected by the treating physician to increase risk of toxicity with AML therapy
* Any concurrent malignancy
* Juvenile myelomonocytic leukemia (JMML)
* Philadelphia chromosome positive AML
* Mixed phenotype acute leukemia
* Acute promyelocytic leukemia
* Acute myeloid leukemia arising from myelodysplasia
* Therapy-related myeloid neoplasms
* Patients with persistent cardiac dysfunction prior to enrollment, defined as ejection fraction (EF) \< 50% (preferred method Biplane Simpson's EF) or if EF unavailable, shortening fraction (SF) \< 24%. \*Note: if clinically safe and feasible, repeat echocardiogram is strongly advised in order to confirm cardiac dysfunction following clinical stabilization, particularly if occurring in the setting of sepsis or other transient physiologic stressor. If the repeat echocardiogram demonstrates an EF \>= 50%, the patient is eligible to enroll and may receive an anthracycline-containing Induction regimen
* Administration of prior anti-cancer therapy except as outlined below:
* Hydroxyurea
* All-trans retinoic acid (ATRA)
* Corticosteroids (any route)
* Intrathecal therapy given at diagnosis
* In particular, strong inducers of CYP3A4 and/or P-glycoprotein (P-gp) should be avoided from the time of enrollment until it is determined whether the patient will receive gilteritinib. Patients receiving gilteritinib will be required to avoid strong CYP3A4 inducers and/or strong P-gp inducers for the duration of the study treatment
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
* ARM D: Patient does not have any congenital long QT syndrome or congenital heart block PROCEDURE: Allogeneic Hematopoietic Stem Cell Transplantation, DRUG: Asparaginase Erwinia chrysanthemi, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Computed Tomography, DRUG: Cytarabine, DRUG: Daunorubicin Hydrochloride, DRUG: Dexrazoxane Hydrochloride, DRUG: Etoposide, OTHER: Fludeoxyglucose F-18, DRUG: Gemtuzumab Ozogamicin, DRUG: Gilteritinib Fumarate, DRUG: Liposome-encapsulated Daunorubicin-Cytarabine, PROCEDURE: Magnetic Resonance Imaging, DRUG: Methotrexate, DRUG: Mitoxantrone Hydrochloride, PROCEDURE: Positron Emission Tomography, OTHER: Questionnaire Administration, DRUG: Therapeutic Hydrocortisone
Acute Myeloid Leukemia, Myeloid and Monocytic Leukemia
Children’s Health
A Study of ASTX030 (Cedazuridine in Combination With Azacitidine) in MDS, CMML, or AML
Study ASTX030-01 is designed to move efficiently from Phase 1 to Phase 3. Phase 1 consists of an open-label Dose Escalation Stage (Stage A) using multiple cohorts at escalating dose levels of oral cedazuridine and azacitidine (only one study drug will be escalated at a time) followed by a Dose Expansion Stage (Stage B). Phase 2 is a randomized, open-label, crossover study to compare oral ASTX030 to subcutaneous (SC) azacitidine. Phase 3 is a randomized open-label crossover study comparing the final oral ASTX030 dose to SC azacitidine. The duration of this phase 1-3 study is approximately 7 years.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
ALL
18 Years and over
PHASE2
NCT04256317
STU-2023-0235
Inclusion Criteria:
Phase 2:
• Has Confirmed MDS, CMML, MDS/MPN or AML diagnosis who are candidates to receive and benefit from single agent azacitidine and as applicable according to local country approvals and/or local institution standard practice. Phase 3:
• Has confirmed MDS or CMML and is a candidate to receive and benefit from single agent azacitidine as applicable according to local country approvals and/or local institution standard practice: a) French-American-British myelodysplastic syndrome subtypes: refractory anemia (RA) or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), and CMML or MDS with intermediate-2 or high risk MDS according to the International Prognostic Scoring System (IPSS).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Participants with adequate organ function.
• For participants with prior allogeneic stem cell transplant, no evidence of graft-versus-host disease (GVHD).
• Participants with no major surgery within 3 weeks before first study treatment.
• Participants with no cytotoxic chemotherapy (excluding hydroxyurea) within 4 weeks before first study treatment.
• Participants with projected life expectancy of at least 12 weeks.
Exclusion Criteria:
Phase 2 and 3:
• Has an active uncontrolled gastric or duodenal ulcer.
• Has poor medical risk because of other conditions.
• Has known human immunodeficiency virus (HIV) infection.
• Is known to be positive for Hepatitis B or C infection.
• Has a life-threatening illness.
• Has a history of other malignancies prior to study entry, with the exception of adequately treated in situ carcinoma of the breast or cervix uteri; localized basal cell carcinoma or squamous cell carcinoma of the skin; previous malignancy confined and surgically resected or adequately treated and controlled with other modalities; and any early stage malignancy for which no definitive therapy is required.
• Participants with MDS/MPN including CMML who have clinical extramedullary disease including clinically palpable hepatomegaly or splenomegaly.
• Has previous treatment with more than 1 cycle of decitabine, azacitidine, or guadecitabine (Phases 2 and 3 only).
• Has been treated with any investigational drug or therapy within 2 weeks, or 5 half-lives, whichever is longer, before the protocol-defined first dose of study treatment, or ongoing clinically significant adverse events from previous treatment with investigational drug or therapy.
• Has a known or suspected hypersensitivity to cedazuridine or azacitidine or any of their excipients.
DRUG: Azacitidine, DRUG: ASTX030 (cedazuridine + azacitidine), DRUG: Azacitidine, DRUG: ASTX030 (cedazuridine + azacitidine), DRUG: Cedazuridine
Myelodysplastic Syndromes, Acute Myeloid Leukemia, Myelodysplastic Syndrome/Neoplasm, Chronic Myelomonocytic Leukemia, Leukemia, Other, Myeloid and Monocytic Leukemia
ASTX030, Myeloid Neoplasm, Hematologic Disease, Leukemia, Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), Chronic Myelomonocytic Leukemia (CMML), Vidaza™, Azacitadine, Azacitadine and cedazuridine drug combination
UT Southwestern
Inotuzumab Ozogamicin and Post-Induction Chemotherapy in Treating Patients With High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and B-LLy
This phase III trial studies whether inotuzumab ozogamicin added to post-induction chemotherapy for patients with High-Risk B-cell Acute Lymphoblastic Leukemia (B-ALL) improves outcomes. This trial also studies the outcomes of patients with mixed phenotype acute leukemia (MPAL), and B-lymphoblastic lymphoma (B-LLy) when treated with ALL therapy without inotuzumab ozogamicin. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a type of chemotherapy called calicheamicin. Inotuzumab attaches to cancer cells in a targeted way and delivers calicheamicin to kill them. Other drugs used in the chemotherapy regimen, such as cyclophosphamide, cytarabine, dexamethasone, doxorubicin, daunorubicin, methotrexate, leucovorin, mercaptopurine, prednisone, thioguanine, vincristine, and pegaspargase or calaspargase pegol work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial will also study the outcomes of patients with mixed phenotype acute leukemia (MPAL) and disseminated B lymphoblastic lymphoma (B-LLy) when treated with high-risk ALL chemotherapy. The overall goal of this study is to understand if adding inotuzumab ozogamicin to standard of care chemotherapy maintains or improves outcomes in High Risk B-cell Acute Lymphoblastic Leukemia (HR B-ALL). The first part of the study includes the first two phases of therapy: Induction and Consolidation. This part will collect information on the leukemia, as well as the effects of the initial treatment, to classify patients into post-consolidation treatment groups. On the second part of this study, patients with HR B-ALL will receive the remainder of the chemotherapy cycles (interim maintenance I, delayed intensification, interim maintenance II, maintenance), with some patients randomized to receive inotuzumab. The patients that receive inotuzumab will not receive part of delayed intensification. Other aims of this study include investigating whether treating both males and females with the same duration of chemotherapy maintains outcomes for males who have previously been treated for an additional year compared to girls, as well as to evaluate the best ways to help patients adhere to oral chemotherapy regimens. Finally, this study will be the first to track the outcomes of subjects with disseminated B-cell Lymphoblastic Leukemia (B-LLy) or Mixed Phenotype Acute Leukemia (MPAL) when treated with B-ALL chemotherapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
ALL
1 Year to 25 Years old
PHASE3
NCT03959085
STU-2019-1574
Inclusion Criteria:
* B-ALL and MPAL patients must be enrolled on APEC14B1 and consented to eligibility studies (Part A) prior to treatment and enrollment on AALL1732. Note that central confirmation of MPAL diagnosis must occur within 22 days of enrollment for suspected MPAL patients. If not performed within this time frame, patients will be taken off protocol.
* APEC14B1 is not a requirement for B-LLy patients but for institutional compliance every patient should be offered participation in APEC14B1. B-LLy patients may directly enroll on AALL1732.
* Patients must be \> 365 days and \< 25 years of age
* White blood cell count (WBC) criteria for patients with B-ALL (within 7 days prior to the start of protocol-directed systemic therapy):
* Age 1-9.99 years: WBC \>= 50,000/uL
* Age 10-24.99 years: Any WBC
* Age 1-9.99 years: WBC \< 50,000/uL with:
* Testicular leukemia
* CNS leukemia (CNS3)
* Steroid pretreatment.
* White blood cell count (WBC) criteria for patients with MPAL (within 7 days prior to the start of protocol-directed systemic therapy):
* Age 1-24.99 years: any WBC NOTE: Patients enrolled as suspected MPAL but found on central confirmatory testing to have B-ALL must meet the B-ALL criteria above (age, WBC, extramedullary disease, steroid pretreatment) to switch to the B-ALL stratum before the end of induction.
* Patient has newly diagnosed B-ALL or MPAL (by World Health Organization \[WHO\] 2016 criteria) with \>= 25% blasts on a bone marrow (BM) aspirate;
* OR If a BM aspirate is not obtained or is not diagnostic of acute leukemia, the diagnosis can be established by a pathologic diagnosis of acute leukemia on a BM biopsy;
* OR A complete blood count (CBC) documenting the presence of at least 1,000/uL circulating leukemic cells if a bone marrow aspirate or biopsy cannot be performed.
* Patient has newly diagnosed B-LLy Murphy stages III or IV.
* Patient has newly diagnosed B-LLy Murphy stages I or II with steroid pretreatment.
* Note: For B-LLy patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to B-ALL. For tissue processed by other means (i.e., paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of B-LLy defined by the submitting institution will be accepted.
* Central nervous system (CNS) status must be determined prior to enrollment based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment and cytoreduction. It is recommended that intrathecal cytarabine be administered at the time of the diagnostic lumbar puncture. This is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture. This is allowed prior to enrollment. Systemic chemotherapy must begin within 72 hours of this intrathecal therapy.
* All patients and/or their parents or legal guardians must sign a written informed consent.
* All institutional, Food and Drug Administration (FDA), and NCI requirements for human studies must be met.
Exclusion Criteria:
* Patients with Down syndrome are not eligible (patients with Down syndrome and B-ALL are eligible for AALL1731, regardless of NCI risk group).
* With the exception of steroid pretreatment and steroid cytoreduction or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for the current diagnosis of B-ALL, MPAL, or B-LLy or for any cancer diagnosed prior to initiation of protocol therapy on AALL1732.
* Patients who have received \> 72 hours of hydroxyurea within one week prior to start of systemic protocol therapy.
* Patients with B-ALL or MPAL who do not have sufficient diagnostic bone marrow submitted for APEC14B1 testing and who do not have a peripheral blood sample submitted containing \> 1,000/uL circulating leukemia cells.
* Patients with acute undifferentiated leukemia (AUL) are not eligible.
* For Murphy stage III/IV B-LLy patients, or stage I/II patients with steroid pretreatment, the following additional exclusion criteria apply:
* T-lymphoblastic lymphoma.
* Morphologically unclassifiable lymphoma.
* Absence of both B-cell and T-cell phenotype markers in a case submitted as lymphoblastic lymphoma.
* Patients with known Charcot-Marie-Tooth disease.
* Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL, regardless of blast immunophenotype.
* Patients requiring radiation at diagnosis.
* Female patients who are pregnant, since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
* Lactating women who plan to breastfeed their infants while on study and for 2 months after the last dose of inotuzumab ozogamicin.
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of study participation. For those patients randomized to inotuzumab ozogamicin, there is a minimum of 8 months after the last dose of inotuzumab ozogamicin for females and 5 months after the last dose of inotuzumab ozogamicin for males. PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Bone Scan, DRUG: Calaspargase Pegol, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, DRUG: Cytarabine, DRUG: Daunorubicin Hydrochloride, DRUG: Dexamethasone, DRUG: Doxorubicin Hydrochloride, BIOLOGICAL: Inotuzumab Ozogamicin, DRUG: Leucovorin Calcium, PROCEDURE: Magnetic Resonance Imaging, DRUG: Mercaptopurine, DRUG: Methotrexate, DRUG: Pegaspargase, PROCEDURE: Positron Emission Tomography, DRUG: Prednisolone, OTHER: Questionnaire Administration, RADIATION: Radiation Therapy, RADIATION: Radiation Therapy, DRUG: Thioguanine, DRUG: Vincristine Sulfate
B Acute Lymphoblastic Leukemia, B Lymphoblastic Lymphoma, Central Nervous System Leukemia, Mixed Phenotype Acute Leukemia, Testicular Leukemia, Leukemia, Other
Children’s Health
Study of Efficacy and Safety of Tisagenlecleucel in HR B-ALL EOC MRD Positive Patients (CASSIOPEIA)
This is a single arm, open-label, multi-center, phase II study to determine the efficacy and safety of tisagenlecleucel in de novo HR pediatric and young adult B-ALL patients who received first-line treatment and are EOC MRD positive. The study will have the following sequential phases: screening, pre-treatment, treatment & follow-up, and survival. After tisagenlecleucel infusion, patient will have assessments performed more frequently in the first month and then at Day 29, then every 3 months for the first year, every 6 months for the second year, then yearly until the end of the study. Efficacy and safety will be assessed at study visits and as clinically indicated throughout the study. The study is expected to end in approximately 8 years after first patient first treatment (FPFT). A post-study long term follow-up safety will continue under a separate protocol per health authority guidelines.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Samuel John
All
1 Year to 25 Years old
Phase 2
NCT03876769
STU-2019-0770
Inclusion Criteria:
• CD19 expressing B-cell Acute Lymphoblastic Leukemia
• De novo NCI HR B-ALL who received first-line treatment and are MRD ≥ 0.01% at EOC. EOC bone marrow MRD will be collected prior to screening and will be assessed by multi-parameter flow cytometry using central laboratory analysis.
• Age 1 to 25 years at the time of screening
• Lansky (age < 16 years) or Karnofsky (age ≥ 16 years) performance status ≥ 60%
• Adequate organ function during the screening period: A. Renal function based on age/gender B. ALT ≤ 5 times ULN for age C. AST ≤ 5 times ULN for age D. Total bilirubin < 2 mg/dL (for Gilbert's Syndrome subjects total bilirubin < 4 mg/dL) E. Adequate pulmonary function defined as:
• no or mild dyspnea (≤ Grade 1)
• oxygen saturation of > 90% on room air F. Adequate cardiac function defined as LVSF ≥ 28% confirmed by echocardiogram or LVEF ≥ 45% confirmed by echocardiogram or MUGA within 6 weeks of screening
• Prior induction and consolidation chemotherapy allowed: 1st line subjects: ≤ 3 blocks of standard chemotherapy for first-line B-ALL, defined as 4-drug induction, Berlin-Frankfurt-Münster (BFM) consolidation or Phase 1b, and interim maintenance with high-dose methotrexate.
Exclusion Criteria:
• M3 marrow at the completion of 1st line induction therapy
• M2 or M3 marrow or persistent extramedullary disease at the completion of first-line consolidation therapy or evidence of disease progression in the peripheral blood or new extramedullary disease prior to enrollment. Patients with previous CNS disease are eligible if there is no active CNS involvement of leukemia at the time of screening.
• Philadelphia chromosome positive ALL
• Hypodiploid: less than 44 chromosomes and/or DNA index < 0.81, or other clear evidence of a hypodiploid clone
• Prior tyrosine kinase inhibitor therapy
• Subjects with concomitant genetic syndromes associated with bone marrow failure states: such as subjects with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome. Subjects with Down syndrome will not be excluded.
• Subjects with Burkitt's lymphoma/leukemia (i.e. subjects with mature B-ALL, leukemia with B-cell [sIg positive and kappa or lambda restricted positivity] ALL, with FAB L3 morphology and /or a MYC translocation)
• Has had treatment with any prior anti-CD19 therapy 9. Treatment with any prior gene or engineered T cell therapy Other protocol-defined inclusion/exclusion may apply.
Biological: CTL019
B-cell Acute Lymphoblastic Leukemia, Lymphoid Leukemia
CTL019, Kymriah, B-Cell Acute Lymphoblastic Leukemia, ALL, tisagenlecleucel, HR B-ALL EOC MRD, Minimal Residual Disease (MRD), Positive at the End of Consolidation (EOC)
Children’s Health
Nivolumab in Treating Patients With Autoimmune Disorders and Advanced, Metastatic, or Unresectable Cancer
This phase Ib trial studies the side effects of nivolumab and to see how well it works in treating patients with autoimmune disorders and cancer that has spread to other places in the body or cannot removed by surgery. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Hans Hammers
ALL
18 Years and over
PHASE1
NCT03816345
STU-2021-0100
Inclusion Criteria:
* Patients can have either histologically confirmed malignancy that is radiologically evaluable and metastatic or unresectable, or have a malignancy for which a PD-1/PD-L1 inhibitor has been approved in the adjuvant setting. Eligible tumor types include solid tumors and malignancies in which there is known evidence of clinical activity for single agent PD-1 or PD-L1 antibodies. Nivolumab is Food and Drug Administration (FDA)-approved for the treatment of melanoma, non-small cell lung cancer (NSCLC), Merkel cell cancer, bladder cancer, renal cell carcinoma (RCC), gastric cancer, hepatocellular carcinoma (HCC), cervical cancer, head and neck cancer, Hodgkin lymphoma (HL), metastatic small cell lung cancer (SCLC), and any solid tumor with microsatellite instability (MSI)-high status confirmed. Patients with HL are eligible but must follow standard response criteria. Additional tumor types may be eligible on a case by case basis upon discussion with principal investigator (PI). Patients enrolling on the trial for adjuvant use will be restricted to those with histology for which a PD-1/PD-L1 inhibitor has been approved in the adjuvant setting including but not limited to NSCLC, melanoma, RCC, cervical cancer, and bladder cancer
* Patients who have previously received other forms of immunotherapy (high-dose \[HD\] IL-2, IFN, CTLA-4) are allowed. Patients must not have received cytokine immunotherapy for at least 4 weeks before nivolumab administration. Patients who have received prior anti-CTLA4 will be allowed and the washout period is 6 weeks
* Age \>= 18 years; children are excluded from this study but may be eligible for future pediatric phase 1 combination trials
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (Karnofsky \>= 60)
* Life expectancy of greater than 12 weeks
* Leukocytes \>= 1,000/mcL
* Absolute neutrophil count \>= 500/mcL
* Platelets \>= 50,000/mcL
* Total bilirubin =\< 2 x institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 5 x institutional ULN or =\< 8 x institutional ULN for patients with liver metastases or an autoimmune disease that is contributing to the elevation of these values
* Creatinine ULN OR glomerular filtration rate (GFR) \>= 30 mL/min (if using the Cockcroft-Gault formula)
* Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial
* If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy if indicated
* If history of hepatitis C virus (HCV) infection, must be treated with undetectable HCV viral load
* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate central nervous system (CNS) specific treatment is not required and is unlikely to be required for at least 4 weeks (or scheduled assessment after the first cycle of treatment), and a risk-benefit analysis (discussion) by the patient and the investigator favors participation in the clinical trial
* The effects of nivolumab on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. WOCBP receiving nivolumab will be instructed to adhere to contraception for a period of 5 months after the last dose of investigational product. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product. Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 24 hours prior to the start of nivolumab. Women must not be breastfeeding. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men) do not require contraception. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL. These durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days, and men who are sexually active with WOCBP use contraception for 5 half-lives plus 90 days. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she (or the participating partner) should inform the treating physician immediately
* Ability to understand and the willingness to sign a written informed consent document
* Patients with more than one autoimmune disease are eligible. The treating physician would determine which autoimmune disease is dominant and the patient would be treated under that specific cohort
Exclusion Criteria:
* Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (AEs) due to agents administered more than 4 weeks earlier have not resolved or stabilized. Palliative (limited-field) radiation therapy (RT) is permitted (2 week washout from start of treatment), if all of the following criteria are met:
* Repeat imaging demonstrates no new sites of bone metastases
* The lesion being considered for palliative radiation is not a target lesion
* Patients with prior therapy with an anti-PD-1 or anti-PD-L1
* Patients with prior allogeneic hematologic transplant
* Patients who are receiving any other anticancer investigational agents
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements PROCEDURE: Biospecimen Collection, BIOLOGICAL: Nivolumab
Autoimmune Disease, Crohn Disease, Dermatomyositis, Hematopoietic and Lymphoid Cell Neoplasm, Inflammatory Bowel Disease, Malignant Solid Neoplasm, Multiple Sclerosis, Psoriasis, Psoriatic Arthritis, Rheumatoid Arthritis, Sjogren Syndrome, Systemic Lupus Erythematosus, Systemic Scleroderma, Ulcerative Colitis, Anus, Bones and Joints, Brain and Nervous System, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Head and Neck, Hodgkins Lymphoma, Kaposis sarcoma, Kidney, Larynx, Leukemia, Not Otherwise Specified, Leukemia, Other, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Lymphoid Leukemia, Lymphoma, Melanoma, skin, Multiple Myeloma, Mycosis Fungoides, Myeloid and Monocytic Leukemia, Non-Hodgkins Lymphoma, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Hematopoietic, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Sarcoma, Small Intestine, Soft Tissue, Stomach, Thyroid, Unknown Sites, Urinary Bladder
UT Southwestern; Parkland Health & Hospital System
Inotuzumab Ozogamicin in Treating Younger Patients With B-Lymphoblastic Lymphoma or Relapsed or Refractory CD22 Positive B Acute Lymphoblastic Leukemia
This phase II trial studies how well inotuzumab ozogamicin works in treating younger patients with B-lymphoblastic lymphoma or CD22 positive B acute lymphoblastic leukemia that has come back (relapsed) or does not respond to treatment (refractory). Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a toxic agent called ozogamicin. Inotuzumab attaches to CD22 positive cancer cells in a targeted way and delivers ozogamicin to kill them.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
ALL
1 Year to 21 Years old
PHASE2
NCT02981628
STU 062017-028
Inclusion Criteria:
* Patients must be \>= 1 year and \< 22 years of age at the time of enrollment
* Patients must have B-ALL, or previously diagnosed B lymphoblastic lymphoma (B-LL), with \>= 5% (M2 or M3) bone marrow blasts with or without extramedullary disease
* NOTE: Relapsed patients previously diagnosed with B-lymphoblastic lymphoma (B-LL) are eligible if they have an M2 or M3 marrow at the time of enrollment on this study
* Patients with ALL or B-LL who have M2 morphology must have local confirmatory testing showing \>= 5% blasts by flow cytometry, fluorescence in situ hybridization (FISH) testing or other molecular method
* Leukemic blasts must demonstrate surface expression of CD22 at the time of relapse by local/institutional flow cytometry of a bone marrow aspirate sample; (assessment of CD22 using a bright fluorophore such as phycoerythrin \[PE\] is strongly recommended)
* In the case of an inadequate aspirate sample (dry tap) or if bone marrow aspirate is unable to be performed due to patient clinical status, flow cytometry of peripheral blood specimen may be substituted if the patient has at least 1,000/uL circulating blasts; alternatively, CD22 expression may be documented by immunohistochemistry of a bone marrow biopsy specimen
* Patients with one of the following:
* Second or greater relapse;
* Primary refractory disease with at least 2 prior induction attempts;
* First relapse refractory to at least one prior re-induction attempt
* Any relapse after HSCT (Cohort 1 ONLY)
Patients with Down syndrome are eligible ONLY for Cohort 1 with:
* Any of above disease status, OR
* First relapse with no prior re-induction attempt NOTE: Patients with Down syndrome or prior HSCT are NOT eligible for Cohort 2 combination therapy
* Patients with Philadelphia chromosome (Ph)+ ALL must have had two prior therapy attempts including two different tyrosine kinase inhibitors (TKIs)
* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy, defined as resolution of all such toxicities to =\< grade 2 or lower per the inclusion/exclusion criteria prior to entering this study. Apply to Cohort 2:
* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment.
* A waiting period prior to enrollment is not required for patients receiving standard cytotoxic maintenance chemotherapy (i.e., corticosteroid, vincristine, 6MP, and/or methotrexate).
* A waiting period is not required for patients receiving a single dose of intrathecal methotrexate, hydrocortisone, and/or cytarabine within 7 days prior to enrollment
* \>= 14 days must have elapsed after the completion of other cytotoxic therapy, with the exception of hydroxyurea, for patients not receiving standard maintenance therapy. For patients who previously received calaspargase pegol, \>= 21 days must have elapsed after the last dose. Additionally, patients must have fully recovered from all acute toxic effects of prior therapy.
* Note: Cytoreduction with hydroxyurea must be discontinued \>= 24 hours prior to the start of protocol therapy.
* Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): \>= 7 days after the last dose of agent. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment.
* Anti-cancer agents that are antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1. There is an exception for blinatumomab infusions, for which patients must have been off for at least 3 days and all drug related toxicity must have resolved to grade 2 or lower as outlined in the inclusion/exclusion criteria.
* Corticosteroids: If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid. A waiting period prior to enrollment is not required for patients receiving corticosteroid for leukemia therapy/cytoreduction.
* Radiotherapy: \>= 2 weeks must have elapsed since local palliative radiation therapy (XRT) (small port); \>= 3 months must have elapsed if prior cranial or craniospinal XRT was received, if \>= 50% of the pelvis was irradiated, or if total body irradiation (TBI) was received; \>= 6 weeks must have elapsed if other substantial bone marrow irradiation was given.
* Stem cell transplant or rescue without TBI: For Cohort 1, at least 90 days must have elapsed since stem cell transplant and at least 30 days from donor lymphocyte infusion. Patient must have had no more than one previous HSCT and currently have no evidence of active graft vs. host disease (GVHD). For Cohort 2, no prior HSCT is allowed.
* Chimeric antigen receptor (CAR) T cell therapy: At least 30 days must have elapsed from the last CAR-T cell infusion
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or
* A serum creatinine based on age/gender as follows:
* 1 to \< 2 years: maximum serum creatinine 0.6 mg/dL (both male and female)
* 2 to \< 6 years: maximum serum creatinine 0.8 mg/dL (both male and female)
* 6 to \< 10 years: maximum serum creatinine 1 mg/dL (both male and female)
* 10 to \< 13 years: maximum serum creatinine 1.2 mg/dL (both male and female)
* 13 to \< 16 years: maximum serum creatinine 1.5 mg/dL (male), 1.4 mg/dL (female)
* \>= 16 years: maximum serum creatinine 1.7 mg/dL (male), 1.4 mg/dL (female)
* Direct bilirubin =\< 1.5 x upper limit of normal (ULN) for age, and
* Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 5 x ULN for age; for the purpose of this study, the ULN for ALT will be 45 U/L
Exclusion Criteria:
* Patients with any prior history of SOS irrespective of severity
* Patients with isolated central nervous system (CNS), testicular, or any other extramedullary site of relapse
* Patients who have been previously treated with inotuzumab ozogamicin
* Patients who have previously received HSCT (Cohort 2 only)
* Patients with Down syndrome (Cohort 2 only)
* History of allergic reaction attributed to compounds of similar or biologic composition to inotuzumab ozogamicin or other agents in the study
* Note: Patients with history of allergy to pegaspargase/calaspargase pegol are eligible for enrollment on Cohort 2 if Erwinia formulation of asparaginase can be obtained
* Patients with active optic nerve and/or retinal involvement are not eligible; patients who are presenting with visual disturbances should have an ophthalmologic exam and, if indicated, a magnetic resonance imaging (MRI) to assess optic nerve or retinal involvement
* Patients who are currently receiving another investigational drug
* Patients who are currently receiving or plan to receive other anti-cancer agents (except hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy, and intrathecal chemotherapy)
* Anti-GVHD or agents to prevent organ rejection post-transplant; patients who are receiving cyclosporine, tacrolimus, or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial; at least 3 half-lives must have elapsed after the last dose of GVHD or anti-rejection medications
* Patients who are currently receiving or plan to receive corticosteroids except as described below
* Systemic corticosteroids may be administered for cytoreduction up to 24 hours prior to the start of protocol therapy, (Cohort 1 only) for all patients, corticosteroids may be administered as a premedication for inotuzumab ozogamicin and as treatment for allergic reactions or for physiologic replacement/stress dosing of hydrocortisone for documented adrenal insufficiency; corticosteroids are not allowed for other indications
* Patients with known human immunodeficiency virus (HIV), hepatitis B or C infections; testing to prove negative status is not required for enrollment unless it is deemed necessary for usual medical care of the patient
* Patients who have an active uncontrolled infection defined as:
* Positive bacterial blood culture within 48 hours of study enrollment;
* Fever above 38.2 degree Celsius (C) within 48 hours of study enrollment with clinical signs of infection; fever that is determined to be due to tumor burden is allowed if patients have documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability
* A positive fungal culture within 30 days of study enrollment or active therapy for presumed invasive fungal infection
* Patients may be receiving IV or oral antibiotics to complete a course of therapy for a prior documented infection as long as cultures have been negative for at least 48 hours and signs or symptoms of active infection have resolved; for patients with clostridium (C.) difficile diarrhea, at least 72 hours of antibacterial therapy must have elapsed and stools must have normalized to baseline
* Active viral or protozoal infection requiring IV treatment
* Patients known to have one of the following concomitant genetic syndromes: Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Schwachman (Schwachman-Diamond-Blackfan) syndrome or any other known bone marrow failure syndrome
* There have been no human studies of inotuzumab ozogamicin in pregnant women and no reports of exposure in utero; based on nonclinical safety studies, inotuzumab ozogamicin has the potential to impair human male and female fertility and to adversely affect human embryo fetal development; women of childbearing potential should be advised to avoid becoming pregnant while receiving inotuzumab ozogamicin; there is no information regarding the presence of inotuzumab ozogamicin in human milk, the effects on the breast-fed infant, or the effects on milk production; because of the potential for adverse reactions in breast-fed infants, women should not breast-feed during treatment with inotuzumab ozogamicin and for at least 2 months after the final dose
* Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained within 7 days prior to enrollment
* Female patients who are sexually active and of reproductive potential are not eligible unless they agree to use an effective contraceptive method for the duration of their study participation and for 8 months after the last dose of inotuzumab ozogamicin
* Men with female partners of childbearing potential should use effective contraception during treatment with inotuzumab ozogamicin and for at least 5 months after the last dose of inotuzumab ozogamicin
* Lactating females are not eligible unless they agree not to breastfeed their infants DRUG: Asparaginase Erwinia chrysanthemi, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration and Biopsy, DRUG: Calaspargase Pegol, DRUG: Cyclophosphamide, DRUG: Cytarabine, PROCEDURE: Diagnostic Imaging, BIOLOGICAL: Inotuzumab Ozogamicin, DRUG: Leucovorin Calcium, PROCEDURE: Lumbar Puncture, DRUG: Methotrexate, DRUG: Pegaspargase, DRUG: Vincristine
Recurrent B Acute Lymphoblastic Leukemia, Recurrent B Lymphoblastic Lymphoma, Refractory B Acute Lymphoblastic Leukemia, Refractory B Lymphoblastic Lymphoma, Leukemia, Other
Children’s Health
Stereotactic Radiosurgery (SRS) Dose-Escalation Study for Brain Metastasis (SRS)
SRS dose escalation for brain metastases in radiation-naïve patients will establish true tolerable doses, which may exceed the current standard doses. This may lead to an improvement in local control, patient survival, and/or quality-of life.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Robert Timmerman
ALL
18 Years and over
NA
NCT02645487
STU 022015-106
Inclusion Criteria
• Biopsy-proven non-hematopoietic malignancy, except for small cell lung cancer, germ cell cancer, or unknown primary tumor.
• Radiographic evidence by MRI (or by CT scan with CT contrast if ineligible or intolerant of MRI) of brain metastasis. (If patient is unable to tolerate MRI contrast, an MRI without contrast is acceptable if lesions are visible)
• All brain metastases must be outside the brain stem (midbrain, pons and medulla).
• Patient must have 10 or less brain metastases.
• The maximum diameter of any lesion must be less than or equal to 3.0 cm.
• Previous treatment with surgery, radiation, chemotherapy, immunotherapy or any targeted agents are allowed provided that: * Radiation was not to the brain. * Surgery to the brain was \> 7 days prior to SRS and there remains at least one additional brain metastasis that can be targeted with SRS
• Age ≥ 18 years.
• ECOG Performance Score of 2 or better/Karnofsky Performance Status score of 50-60 or better.
• All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Ability to understand and the willingness to sign a written informed consent. Exclusion Criteria
• Patients had craniotomy and surgery to the brain within 7 days from the date of SRS.
• Patients with leptomeningeal metastasis. NOTE: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive CSF cytology and/or equivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology, unless a parenchymal lesion can adequately explain the neurologic symptoms and/or signs. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion.
• Patients with a contraindication to both MRI (with or without contrast) and CT scan (with contrast)
• Patients with life expectancy \< 3 months.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects must not be pregnant or nursing at the time of SRS treatment due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• Biopsy-proven non-hematopoietic malignancy, except for small cell lung cancer, germ cell cancer, or unknown primary tumor.
• Radiographic evidence by MRI (or by CT scan with CT contrast if ineligible or intolerant of MRI) of brain metastasis. (If patient is unable to tolerate MRI contrast, an MRI without contrast is acceptable if lesions are visible)
• All brain metastases must be outside the brain stem (midbrain, pons and medulla).
• Patient must have 10 or less brain metastases.
• The maximum diameter of any lesion must be less than or equal to 3.0 cm.
• Previous treatment with surgery, radiation, chemotherapy, immunotherapy or any targeted agents are allowed provided that: * Radiation was not to the brain. * Surgery to the brain was \> 7 days prior to SRS and there remains at least one additional brain metastasis that can be targeted with SRS
• Age ≥ 18 years.
• ECOG Performance Score of 2 or better/Karnofsky Performance Status score of 50-60 or better.
• All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Ability to understand and the willingness to sign a written informed consent. Exclusion Criteria
• Patients had craniotomy and surgery to the brain within 7 days from the date of SRS.
• Patients with leptomeningeal metastasis. NOTE: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive CSF cytology and/or equivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology, unless a parenchymal lesion can adequately explain the neurologic symptoms and/or signs. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion.
• Patients with a contraindication to both MRI (with or without contrast) and CT scan (with contrast)
• Patients with life expectancy \< 3 months.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects must not be pregnant or nursing at the time of SRS treatment due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
RADIATION: Stereotactic Radiosurgery
Brain Neoplasms, Adult, Malignant, Brain and Nervous System, Anklylosing Spondylitis, Anus, Bones and Joints, Breast - Female, Breast - Male, Cardiovascular, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Eye and Orbit, Gall Bladder, Head and Neck, Hodgkins Lymphoma, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Lymphoid Leukemia, Lymphoma, Melanoma, skin, Multiple Myeloma, Nose, Other, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Sarcoma, Small Intestine, Soft Tissue, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva
UT Southwestern; Parkland Health & Hospital System
CAR-T Long Term Follow Up (LTFU) Study (PAVO)
Per Health Authorities guidelines for gene therapy medicinal products that utilize integrating vectors (e.g. lentiviral vectors), long term safety and efficacy follow up of treated patients is required. The purpose of this study is to monitor all patients exposed to CAR-T therapied for 15 years following their last CAR-T (e.g. CTL019) infusion to assess the risk of delayed adverse events (AEs), monitor for replication competent lentivirus (RCL) and assess long-term efficacy, including vector persistence.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Samuel John
ALL
Not specified
PHASE3
NCT02445222
STU 032015-068
Inclusion Criteria:
* All patients who have received a CAR-T therapy and completed or discontinued early from a Novartis sponsored treatment protocol that utilized CAR-T cells or from any CAR-T trial sponsored by the University of Pennsylvania with which Novartis has a contractual agreement to co-develop the CAR technology.
* Patients who have provided informed consent for the long term follow up study prior to their study participation .
Exclusion Criteria:
* There are no specific exclusion criteria for this study. GENETIC: Previously treated CAR-T patients
Long Term Safety of Patients Receiving CAR-T in an Eligible Clinical Trial or Managed Access Program, Leukemia, Other
Children’s Health
Vincristine Sulfate Liposome Injection (Marqibo®) in Combination With UK ALL R3 Induction Chemotherapy for Children, Adolescents, and Young Adults With Relapsed ALL
This is a pilot study utilizing Marqibo® (vincristine sulfate liposome injection) combined with dexamethasone, mitoxantrone and asparaginase (UK ALL R3) for relapsed acute lymphoblastic leukemia (ALL).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
All
1 Year to 21 Years old
Phase 1
NCT02879643
STU 082016-009
Inclusion Criteria
Age
-Patients must be ≥ 1 and ≤ 21 years of age at the time of enrollment.
Diagnosis
• Cohort A: Patients must have a diagnosis of acute lymphoblastic leukemia (ALL) or mixed phenotypic acute leukemia with ≥ 5% blasts in the bone marrow (M2 or M3), with or without extramedullary disease) or a diagnosis of lymphoblastic lymphoma.
• Cohorts B & C: Patients must have a diagnosis of acute lymphoblastic leukemia (ALL), lymphoblastic lymphoma, or mixed phenotypic acute leukemia with any level of detectable disease (minimal residual disease level acceptable) with or without extramedullary disease Performance Level -Karnofsky > 50% for patients > 16 years of age and Lansky > 50% for patients ≤ 16 years of age. Prior Therapy
• Patients must have recovered from the acute toxic effects (≤ Grade 2 or baseline) of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study, unless otherwise specified. Subjects with disease related cytopenias will be eligible.
• Patients must have relapsed or refractory disease after attaining at least a first remission. They may be in first to third relapse..
• Patients with Philadelphia chromosome t(9;22) positive disease must have received at least two prior tyrosine kinase inhibitors.
• Patients who have experienced their relapse after a Hematopoietic stem cell transplantation (HSCT) are eligible, provided they have no evidence of graft-versus-host disease (GVHD) and are at least 100 days post-transplant at the time of enrollment.
• Prior anthracycline lifetime cumulative exposure: Patients must have less than 320 mg/m2 (or 400 mg/m2 if prior cardioprotection) lifetime exposure of anthracycline chemotherapy.
• Cohort A: Patients must have less than 320 mg/m2 (or 400 mg/m2 if prior cardioprotection) lifetime exposure of anthracycline chemotherapy (See Appendix 2 for anthracycline calculation worksheet).
• Cohorts B & C: There is no limit on prior anthracycline exposure.
• Hematopoietic growth factors: It must have been at least seven days since the completion of therapy with granulocyte colony-stimulating factor (GCSF) or other growth factors at the time of enrollment. It must have been at least 14 days since the completion of therapy with pegfilgrastim (Neulasta®).
• Biologic anti-neoplastic agents: At least seven days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond seven days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair or vice chair.
• Monoclonal antibodies: At least three half-lives (or 30 days—whichever is longer) of the antibody must have elapsed after the last dose of monoclonal antibody. (e.g., Rituximab = 66 days, Epratuzumab = 69 days)
• Immunotherapy: At least 30 days after the completion of any type of immunotherapy, e.g. tumor vaccines, chimeric antigen receptor T-cells.
• Recent prior chemotherapy: At least 10 days after standard vincristine and the completion of any type of chemotherapy induction regimen. At least 3 weeks after radiation therapy. At least 30 days after the completion of any investigational neoplastic agent is also required. An investigational agent is defined as any drug that is not approved and licensed for sale by the FDA for institutions in the United States, by Health Canada for institutions in Canada and by The Therapeutic Goods Administration for institutions in Australia. Exceptions:
• There is no time restriction in regard to prior intrathecal chemotherapy provided there is complete recovery from any acute toxic effects of such; it is allowable to enroll a patient that has received IT Cytarabine (ARA-C), IT Methotrexate (MTX) or triple IT therapy within 14 days of enrollment as part of their evaluation to diagnose disease relapse. The IT therapy given within 14 days of initiation of protocol specified chemotherapy, may substitute for the day 1 IT in cohorts A and B
• Subjects with rapidly progressive disease may receive hydroxyurea until they begin study therapy;
• Patients who relapse while on maintenance-type ALL therapy or are receiving maintenance therapy for disease stabilization will not require a wash-out period before entry into this study. However, there must be at least 10 days after any dose of standard vincristine. Renal and Hepatic Function
• Renal function: Patient's serum creatinine must be ≤ 1.5 x institutional upper limit of normal (ULN) according to age. If the serum creatinine is greater than 1.5 times normal, the patient must have a calculated creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70milliliter/min/1.73m2. Alternatively, a 24-hour creatinine clearance may also be used.
• Hepatic function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be < 5 x institutional upper limit of norm ULN. Total bilirubin must be ≤ 1.5 x ULN (except in the case of subjects with documented Gilbert's disease ≤ 5 × ULN). Cardiac Function -Patients must have a shortening fraction ≥ 27% or an ejection fraction ≥ 55% by echocardiogram, cardiac MRI or multigated acquisition scan (MUGA). Reproductive Function
• Female patients must not be pregnant and those of childbearing potential must have a negative urine or serum pregnancy test confirmed within one week prior to enrollment.
• Female patients with infants must agree not to breastfeed their infants while on this study.
• Male and female patients of childbearing potential must agree to use an effective method of contraception during the study. Exclusion Criteria Patients will be excluded if they have isolated testicular disease. Patients will be excluded if they have previously received Marqibo®. Patients will be excluded if they have a known allergy to any of the drugs used in the study, with the exception that patients with an allergy to PEG-asparaginase who can receive Erwinia asparaginase are eligible. Patients unable to receive any formulation of asparaginase may only enroll on cohort C Patients will be excluded if they have active, uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics or other treatment. Patients who require azole antifungal agents will be excluded. Azoles must be discontinued at least one week prior to the start of Marqibo®. Patients will be excluded if there is a plan to administer non-protocol chemotherapy, radiation therapy, another investigational agent or immunotherapy during the study period. Patients with pre-existing, persistent grade 2 or greater sensory or motor neuropathy from any cause will be excluded. Patients will be excluded if they have, significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or adherence with the protocol treatment or procedures or interfere with consent, study participation, follow up, or interpretation of study results.Patients with Down syndrome will not be eligible for enrollment on Cohort A Patients with a known history of human immunodeficiency virus (HIV) will will be excluded due to the increased risk of complications such as severe infection and unknown interaction of Marqibo® with antiretroviral drugs. Active hepatitis B or C infection as defined by seropositive for hepatitis B (hepatitis B surface antigen (HBsAg)) or hepatitis C and elevated liver transaminases (defined as above the ULN per the institution normal ranges).
• Cohort A: Patients must have a diagnosis of acute lymphoblastic leukemia (ALL) or mixed phenotypic acute leukemia with ≥ 5% blasts in the bone marrow (M2 or M3), with or without extramedullary disease) or a diagnosis of lymphoblastic lymphoma.
• Cohorts B & C: Patients must have a diagnosis of acute lymphoblastic leukemia (ALL), lymphoblastic lymphoma, or mixed phenotypic acute leukemia with any level of detectable disease (minimal residual disease level acceptable) with or without extramedullary disease Performance Level -Karnofsky > 50% for patients > 16 years of age and Lansky > 50% for patients ≤ 16 years of age. Prior Therapy
• Patients must have recovered from the acute toxic effects (≤ Grade 2 or baseline) of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study, unless otherwise specified. Subjects with disease related cytopenias will be eligible.
• Patients must have relapsed or refractory disease after attaining at least a first remission. They may be in first to third relapse..
• Patients with Philadelphia chromosome t(9;22) positive disease must have received at least two prior tyrosine kinase inhibitors.
• Patients who have experienced their relapse after a Hematopoietic stem cell transplantation (HSCT) are eligible, provided they have no evidence of graft-versus-host disease (GVHD) and are at least 100 days post-transplant at the time of enrollment.
• Prior anthracycline lifetime cumulative exposure: Patients must have less than 320 mg/m2 (or 400 mg/m2 if prior cardioprotection) lifetime exposure of anthracycline chemotherapy.
• Cohort A: Patients must have less than 320 mg/m2 (or 400 mg/m2 if prior cardioprotection) lifetime exposure of anthracycline chemotherapy (See Appendix 2 for anthracycline calculation worksheet).
• Cohorts B & C: There is no limit on prior anthracycline exposure.
• Hematopoietic growth factors: It must have been at least seven days since the completion of therapy with granulocyte colony-stimulating factor (GCSF) or other growth factors at the time of enrollment. It must have been at least 14 days since the completion of therapy with pegfilgrastim (Neulasta®).
• Biologic anti-neoplastic agents: At least seven days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond seven days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair or vice chair.
• Monoclonal antibodies: At least three half-lives (or 30 days—whichever is longer) of the antibody must have elapsed after the last dose of monoclonal antibody. (e.g., Rituximab = 66 days, Epratuzumab = 69 days)
• Immunotherapy: At least 30 days after the completion of any type of immunotherapy, e.g. tumor vaccines, chimeric antigen receptor T-cells.
• Recent prior chemotherapy: At least 10 days after standard vincristine and the completion of any type of chemotherapy induction regimen. At least 3 weeks after radiation therapy. At least 30 days after the completion of any investigational neoplastic agent is also required. An investigational agent is defined as any drug that is not approved and licensed for sale by the FDA for institutions in the United States, by Health Canada for institutions in Canada and by The Therapeutic Goods Administration for institutions in Australia. Exceptions:
• There is no time restriction in regard to prior intrathecal chemotherapy provided there is complete recovery from any acute toxic effects of such; it is allowable to enroll a patient that has received IT Cytarabine (ARA-C), IT Methotrexate (MTX) or triple IT therapy within 14 days of enrollment as part of their evaluation to diagnose disease relapse. The IT therapy given within 14 days of initiation of protocol specified chemotherapy, may substitute for the day 1 IT in cohorts A and B
• Subjects with rapidly progressive disease may receive hydroxyurea until they begin study therapy;
• Patients who relapse while on maintenance-type ALL therapy or are receiving maintenance therapy for disease stabilization will not require a wash-out period before entry into this study. However, there must be at least 10 days after any dose of standard vincristine. Renal and Hepatic Function
• Renal function: Patient's serum creatinine must be ≤ 1.5 x institutional upper limit of normal (ULN) according to age. If the serum creatinine is greater than 1.5 times normal, the patient must have a calculated creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70milliliter/min/1.73m2. Alternatively, a 24-hour creatinine clearance may also be used.
• Hepatic function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be < 5 x institutional upper limit of norm ULN. Total bilirubin must be ≤ 1.5 x ULN (except in the case of subjects with documented Gilbert's disease ≤ 5 × ULN). Cardiac Function -Patients must have a shortening fraction ≥ 27% or an ejection fraction ≥ 55% by echocardiogram, cardiac MRI or multigated acquisition scan (MUGA). Reproductive Function
• Female patients must not be pregnant and those of childbearing potential must have a negative urine or serum pregnancy test confirmed within one week prior to enrollment.
• Female patients with infants must agree not to breastfeed their infants while on this study.
• Male and female patients of childbearing potential must agree to use an effective method of contraception during the study. Exclusion Criteria Patients will be excluded if they have isolated testicular disease. Patients will be excluded if they have previously received Marqibo®. Patients will be excluded if they have a known allergy to any of the drugs used in the study, with the exception that patients with an allergy to PEG-asparaginase who can receive Erwinia asparaginase are eligible. Patients unable to receive any formulation of asparaginase may only enroll on cohort C Patients will be excluded if they have active, uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics or other treatment. Patients who require azole antifungal agents will be excluded. Azoles must be discontinued at least one week prior to the start of Marqibo®. Patients will be excluded if there is a plan to administer non-protocol chemotherapy, radiation therapy, another investigational agent or immunotherapy during the study period. Patients with pre-existing, persistent grade 2 or greater sensory or motor neuropathy from any cause will be excluded. Patients will be excluded if they have, significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or adherence with the protocol treatment or procedures or interfere with consent, study participation, follow up, or interpretation of study results.Patients with Down syndrome will not be eligible for enrollment on Cohort A Patients with a known history of human immunodeficiency virus (HIV) will will be excluded due to the increased risk of complications such as severe infection and unknown interaction of Marqibo® with antiretroviral drugs. Active hepatitis B or C infection as defined by seropositive for hepatitis B (hepatitis B surface antigen (HBsAg)) or hepatitis C and elevated liver transaminases (defined as above the ULN per the institution normal ranges).
Drug: Marqibo
ALL, Childhood, Lymphoblastic Leukemia, Acute, Childhood, Lymphoblastic Leukemia, Acute, Lymphoid Leukemia
Children’s Health