StudyFinder
Search Results Within Category "Blood Disorders"
46 Study Matches
VITAS: Atezolizumab in Combination With Chemotherapy for Pediatric Relapsed/Refractory Solid Tumors
This trial is a multi-center, non-randomized, open-label Phase I/II study evaluating the feasibility and efficacy of vincristine, irinotecan, temozolomide, and atezolizumab in children with relapsed/refractory solid tumors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Arhanti Sadanand
ALL
6 Months to 30 Years old
PHASE1
NCT04796012
STU-2021-0606
Inclusion Criteria:
• Signed informed consent
• Relapsed or refractory solid tumor after at least one prior course of therapy.
• Hodgkin lymphoma or non-Hodgkin lymphoma are not permitted.
• Patients with CNS malignancy or asymptomatic CNS metastases may be enrolled, provided all of the following criteria are met. * No metastatic or primary disease affecting the brainstem, midbrain, pons, or cerebellum, or within 10 mm of optic nerve * No history of leptomeningeal disease * No history of intracranial or spinal cord hemorrhage * No evidence of progression of neurologic deficit, in the investigator's judgment, within 7 days prior to initiation of study medications.
• Must have histologically confirmed rhabdomyosarcoma (RMS) for RMS efficacy cohort.
• Age ≥ 6 months and ≤ 30 years
• Lansky Performance Status (patients \< 16 years old) or Karnofsky Performance Status (patients ≥ 16 years old) ≥ 50
• Ability to comply with the study protocol, in the investigator's judgment
• For RMS efficacy cohort, disease must be measurable as defined by RECIST v1.1.
• For the feasibility cohort, disease must be evaluable, but patients enrolled in the feasibility cohort will be prospectively assessed for measurable disease, RMS patients will also be included in the RMS efficacy cohort.
• Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation.
• Availability of a tumor specimen suitable for determination of PD-L1 status, either from initial diagnosis or from a recurrence.
• For PD-L1 staining to be performed at the central site, a formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 15 slides containing unstained, freshly cut, serial sections must be available along with an associated pathology report prior to study enrollment.
• Patients for whom the required number of slides are not available may still be eligible to enroll on study with PI approval
• For the RMS efficacy cohort, it will be required that at least 8 of 17 patients have PD-L1(+) tumor. PD-L1 status will be determined at time of enrollment for all patients. When the maximum allowable number of PD-L1(-) patients has been enrolled and treated on study, PD-L1 positivity will be required for all further enrolled patients.
• Staining will be performed in the central site CAP/CLIA-certified laboratory using the 22c3 antibody for immunohistochemical analysis
• PD-L1(+) status will be defined as staining on ≥1% of tumor cells or ≥1% of stroma.
• For the feasibility cohort, PD-L1 positivity is not required but will be performed centrally in all cases for exploratory biomarker studies.
• Adequate organ and marrow function as defined by the following laboratory values obtained within 21 days prior to initiation of study medication.
• For patients without known bone marrow involvement: * Absolute neutrophil count ≥ 1.0 x 10\^9 / L (1000/µL) without granulocyte colony-stimulating factor support (≥14 days after the last dose of a long-acting growth factor such as pegfilgrastim, or 7 days after short-acting growth factor) * Platelet count ≥ 75 x 10\^9 / L (75,000/µL) without transfusion in the last 7 days
• Patients with known bone marrow metastatic disease will be eligible for the study if they meet the following criteria: * Patients with documented liver metastases: AST and ALT ≤ 5 x ULN * Patients with documented liver or bone metastases: ALP ≤ 5 x ULN * Absolute neutrophil count (ANC) ≥ 750/mm\^3 * Platelet count ≥ 50,000/mm\^3 (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions) * These patients will not be evaluable for hematologic toxicity. At least 4 of 6 patients in the feasibility cohort must be evaluable for hematologic toxicity. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity.
• Total bilirubin ≤1.5 x upper limit of normal (ULN) for age (Patients with known Gilbert disease: serum bilirubin ≤ 3 x ULN)
• AST (SGOT) and ALT (SPGT) ≤ 2.5 x ULN for age
• Serum albumin ≥ 25 g/L (2.5 g/dL)
• Creatinine ≤ 1.5 x ULN for age or creatinine clearance (or radioisotope glomerular filtration rate) ≥ 70 mL/min/1.73 m2
• Left ventricular ejection fraction ≥ 50% or shortening fraction ≥ 30%
• Hemoglobin ≥ 90 g/L (9 g/dL)
• Patients may be transfused to meet this criterion.
• For patients not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN
• For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
• Negative HIV and hepatitis B surface antigen (HBsAg) tests at screening
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs, as defined below:
• Women must remain abstinent or use contraceptive methods with a failure rate of \< 1% per year during the treatment period and for 5 months after the final doses of atezolizumab, vincristine, and temozolomide. Women must refrain from donating eggs during this same period.
• A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus), regardless of sexual orientation or marital status.
• Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
• The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception.
• For men who are not surgically sterile: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:
• With a female partner of childbearing potential who is not pregnant, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of less 1% per year during the treatment period and for 5 months after the final doses of atezolizumab, irinotecan, and temozolomide. Men must refrain from donating sperm during this same period.
• The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception
Exclusion Criteria:
• Pregnancy or breast-feeding:
• Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of study treatment
• Women of childbearing potential must have a negative serum pregnancy test result within 21 days prior to initiation of study treatment.
• Medical conditions that are excluded:
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Guillain-Barré syndrome, multiple sclerosis, or Kawasaki syndrome with the following exceptions: * Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study. * Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study. * Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met at study initiation: (1) Rash must cover less 10% of body surface area, (2) Disease is well controlled at baseline and requires only low-potency topical corticosteroids, (3) No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
• Uncontrolled or symptomatic hypercalcemia (ionized calcium \> 1.5 mmol/L, calcium \> 12 mg/dL or corrected serum calcium \> ULN)
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) * Patients with indwelling catheters (e.g., PleurX®) are allowed.
• Uncontrolled tumor-related pain * Patients requiring pain medication must be on a stable regimen at study entry for at least 2 weeks. Intermittent use of as-needed medication is allowed during this period.
• Clinically significant gastrointestinal disorder that may interfere with absorption of orally administered drugs (at the discretion of the treating physician)
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan * History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
• History of severe asthma or uncontrolled asthma
• Dyspnea at rest or requirement for supplemental oxygen
• Uncontrolled seizures. Patients taking a stable dose of anticonvulsants (for 2 weeks) are permitted, as long as they are not strong inducers or inhibitors of CYP3A4.
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications in the opinion of the treating investigator
• Washout periods from prior therapies:
• Myelosuppressive chemotherapy or radiotherapy within 21 days prior to starting study treatment. * Subjects must have recovered from all acute prior treatment-related toxicities to grade 1 or baseline (excluding alopecia and clinically stable toxicities requiring ongoing medical management, such as hypothyroidism).
• Non-myelosuppressive cancer therapy, such as kinase inhibitors, within 7 days prior to study treatment.
• Treatment with monoclonal antibodies with long half-lives, within 3 half-lives prior to study treatment.
• Treatment with targeted cellular therapies within 28 days prior to starting study treatment.
• Major surgical procedure, other than for diagnosis, within 30 days prior to initiation of study treatment, or anticipation of the need for a major surgical procedure during the first four cycles of the study. * Biopsy tissue collection or placement of a vascular access device is permitted if the site has healed prior to initiation of study medications. * For patients with CNS disease, no neurosurgical resection, brain biopsy, or stereotactic/whole-brain radiation within 30 days prior to Cycle 1, Day 1
• Treatment with a live, attenuated vaccine within 30 days prior to initiation of study treatment, or anticipation of the need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab
• Treatment with investigational therapy within 21 days prior to initiation of study treatment or concurrent participation with another investigational agent
• Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \[IL-2\]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
• Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-agents) within 2 weeks prior to initiation of study treatment, or anticipation of the need for systemic immunosuppressive medication during study treatment, with the following exceptions: * Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after Principal Investigator confirmation has been obtained. * Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study. * Patients with CNS disease can be receiving concurrent treatment with corticosteroids with approval from the Principal Investigator. Patients must be receiving a stable or decreasing dose for ≥ 5 days prior to the baseline MRI scan and at the time of drug initiation. The Principal Investigator should be informed when steroid doses are increased because of declining patient status.
• Use of strong CYP3A4 inhibitors or inducers or strong UGT1A1 inhibitors within 12 days of Cycle 1, Day 1.
• Treatment with high-dose chemotherapy and hematopoietic stem-cell rescue within 3 months prior to initiation of study drug
• Treatment with herbal cancer therapy within 1 week prior to initiation of study medications.
• Treatment with a long-acting hematopoietic growth factor (such as pegfilgrastim) within 2 weeks prior to initiation of study medications, or a short-acting hematopoietic growth factor (such as G-CSF) within 1 week prior to initiation of study medications.
• Prior treatments:
• Prior allogeneic stem cell or solid organ transplantation
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies to include all anti-PD-1, and anti-PD-L1 therapeutic antibodies
• Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \[IL-2\] within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
• Subjects must not have previously progressed while receiving regimens that include irinotecan or temozolomide. Patients who have received irinotecan or temozolomide and did not progress while on these medications are eligible.
• Known ongoing or untreated infection, including, but not limited to bacteremia, active tuberculosis, or severe pneumonia
• Active tuberculosis
• Current treatment with anti-viral therapy for HBV
• Active hepatitis C
• Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study
• Known allergy or hypersensitivity to any component of the study medications
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
DRUG: Atezolizumab, DRUG: Vincristine, DRUG: Irinotecan, DRUG: Temozolomide
Solid Tumor, Rhabdomyosarcoma, Brain and Nervous System, Colon, Lymphoma, Soft Tissue
Relapsed solid tumor, Refractory solid tumor, Rhabdomyosarcoma
UT Southwestern; Children’s Health
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 before C1D1 (the first dose of study treatment)
* 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 Human immunodeficiency virus (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 Chronic lymphocytic leukemia/ Small lymphocytic lymphoma (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. NOTE: As of Protocol Amendment 09, at least 10 CLL/SLL participants whose disease relapsed or was refractory to prior therapy with a covalent/irreversible BTKi, BCL2i and noncovalent/reversible BTKi (all three classes of therapies are required) will be enrolled into Cohort J
* Has active disease for CLL/SLL clearly documented to initiate therapy
* For SLL participants in Part 2: 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 Mantle-cell lymphoma (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 Marginal zone lymphoma (MZL) (including splenic, nodal, and extra nodal MZL) who are relapsed or refractory to at least one prior line of systemic therapy including an anti-CD20-based regimen
* Participants with Follicular lymphoma (FL) who are relapsed or refractory to chemoimmunotherapy and immunomodulatory agents (such as lenalidomide based regimen) (Cohort G)
* Have measurable disease defined as at least 1 lesion that can be accurately measured in at least 2 dimensions with spiral Computed tomography (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 Waldenström's macroglobulinemia (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 (e.g., 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 5 half-lives or 4 weeks (if prior therapy was a monoclonal antibody) before C1D1
* 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
POCUS: Hemostatic Potential and Joint Health in Patients With Severe Hemophilia A on Novel Replacement Therapies
This is a prospective, randomized control trial in which each patient will be randomly assigned to receive either extended half-life factor VIII based replacement therapy or non-FVIII based replacement therapy, which are both standard of care treatment for persons with Hemophilia A.
Call 214-648-5005
studyfinder@utsouthwestern.edu, lindsey.hartland@childrens.com
Jessica Garcia
ALL
up to 17 Years old
PHASE4
NCT04690322
STU-2020-1378
Inclusion Criteria:
* Subjects with moderate hemophilia A (baseline factor VIII activity 1-5%) or severe hemophilia A (baseline factor VIII activity \<1%) on prophylactic standard half-life FVIII infusions OR subjects with moderate or severe hemophilia A who have not started prophylactic treatment
* Less than 18 years of age
Exclusion Criteria:
* Subjects with documented FVIII inhibitor
* Subjects with a history of ≥ 2 target joints
* Subjects with a history of synovectomy
* Currently using medications known to impact bone and mineral metabolism (e.g., bisphosphonates, corticosteroids, estrogen, testosterone, calcitonin, thyroid hormone therapy);
* Disease states known to affect bone integrity (e.g., primary hyperparathyroidism, Paget's disease, clinically significant liver disease) DRUG: Eloctate, DRUG: Adynovate, DRUG: Emicizumab
Hemophilia A, Factor VIII, Bones and Joints, Other Hematopoietic
Children’s Health
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
Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs Administered to Children Per Standard of Care (POPS) (POPS or POP02)
The study investigators are interested in learning more about how drugs, that are given to children by their health care provider, act in the bodies of children and young adults in hopes to find the most safe and effective dose for children. The primary objective of this study is to evaluate the PK of understudied drugs currently being administered to children per SOC as prescribed by their treating provider.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Aruna.Ayalasomayajula@UTSouthwestern.edu
Mia Maamari
ALL
0 Years to 20 Years old
NCT04278404
STU-2021-0176
Inclusion Criteria:
• Participant is \< 21 years of age
• Parent/ Legal Guardian/ Adult Participant can understand the consent process and is willing to provide informed consent/HIPAA:
• (a) Participant is receiving one or more of the study drugs of interest at the time of enrollment or (b) Participant is NOT receiving one or more of the study drugs of interest but is SARS-COV-2 positive within 60 days prior to enrollment
Exclusion Criteria:
• Participant has a known pregnancy Below exclusion criteria apply only to: Participants receiving one or more of the study drugs of interest at the time of enrollment, DOI administration or PK sampling: (Refer to DOI specific appendices for details on enrollment cohort specifications and additional eligibility criteria)
• Has had intermittent dialysis within previous 24 hours
• Has had a kidney transplant within previous 30 days
• Has had a liver transplant within previous 1 year
• Has had a stem cell transplant within previous 1 year
• Has had therapeutic hypothermia within previous 24 hours
• Has had plasmapheresis within the previous 24 hours
• Has a Ventricular Assist Device
• Has any condition which would make the participant, in the opinion of the investigator, unsuitable for the study
DRUG: The POP02 study is collecting bodily fluid samples (i.e., whole blood, effluent samples) of children prescribed the following drugs of interest per standard of care:
Coronavirus Infection (COVID-19), Pulmonary Arterial Hypertension, Urinary Tract Infections in Children, Hypertension, Pain, Hyperphosphatemia, Primary Hyperaldosteronism, Edema, Hypokalemia, Heart Failure, Hemophilia, Menorrhagia, Insomnia, Pneumonia, Skin Infection, Arrythmia, Asthma in Children, Bronchopulmonary Dysplasia, Adrenal Insufficiency, Fibrinolysis, Hemorrhage, Attention Deficit Hyperactivity Disorder, Multisystem Inflammatory Syndrome in Children (MIS-C), Kawasaki Disease, Coagulation Disorder, Down Syndrome
Children’s Health
A Study of Repotrectinib in Pediatric and Young Adult Subjects Harboring ALK, ROS1, OR NTRK1-3 Alterations
Phase 1 will evaluate the safety and tolerability at different dose levels of repotrectinib in pediatric and young adult subjects with advanced or metastatic malignancies harboring anaplastic lymphoma kinase (ALK), receptor tyrosine kinase encoded by the gene ROS1 (ROS1), or neurotrophic receptor kinase genes encoding TRK kinase family (NTRK1-3) alterations to estimate the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) and select the Pediatric Recommended Phase 2 Dose (RP2D). Phase 2 will determine the anti-tumor activity of repotrectinib in pediatric and young adult subjects with advanced or metastatic malignancies harboring ROS1 or NTRK1-3 alterations.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tanya Watt
ALL
up to 25 Years old
PHASE1
NCT04094610
STU-2019-1268
Key
• Documented genetic ROS1 point mutation, fusion, or amplification or NTRK1-3 fusion as identified by local testing in a Clinical Laboratory Improvement Amendments (CLIA) laboratory in the US or equivalently accredited diagnostic lab outside the United States (US) is required.
• Phase 1: Age \<12 years; Phase 2: Age 12- 25 years
• Prior cytotoxic chemotherapy is allowed.
• Prior immunotherapy is allowed.
• Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
• All subjects must have measurable disease by RECIST v1.1 or Response Assessment in Neuro-Oncology (RANO) criteria at time of enrollment.
• Subjects with a primary CNS tumor or CNS metastases must be neurologically stable on a stable or decreasing dose of steroids for at least 7 days prior to enrollment.
• Subjects must have a Lansky (\< 16 years) or Karnofsky (≥ 16 years) score of at least 50.
• Life expectancy greater than or equal to 12 weeks, in the investigator's opinion.
• Adequate hematologic, renal and hepatic function. Phase 2
• Cohort Specific
• Subjects in Cohorts 1 and 2 must have prospectively confirmed measurable disease by BICR prior to enrollment. Key Exclusion Criteria (Phase 1 and Phase 2):
• Subjects with neuroblastoma with only bone marrow disease evaluable by bone marrow aspiration only.
• Major surgery within 14 days (2 weeks) of start of repotrectinib treatment. Central venous access (Broviac, Mediport, etc.) placement does not meet criteria for major surgery.
• Known active infections requiring ongoing treatment (bacterial, fungal, viral including HIV positivity).
• Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
• Any of the following cardiac criteria: * Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTc) \> 480 msec obtained from three ECGs, using the screening clinic ECG machine-derived QTc value * Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval \> 250 msec) * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval
• Peripheral neuropathy of CTCAE ≥grade 2.
• Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers.
• Any potential allergies to repotrectinib and/or its excipients.
Inclusion Criteria:
• Documented genetic ROS1 point mutation, fusion, or amplification or NTRK1-3 fusion as identified by local testing in a Clinical Laboratory Improvement Amendments (CLIA) laboratory in the US or equivalently accredited diagnostic lab outside the United States (US) is required.
• Phase 1: Age \<12 years; Phase 2: Age 12- 25 years
• Prior cytotoxic chemotherapy is allowed.
• Prior immunotherapy is allowed.
• Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
• All subjects must have measurable disease by RECIST v1.1 or Response Assessment in Neuro-Oncology (RANO) criteria at time of enrollment.
• Subjects with a primary CNS tumor or CNS metastases must be neurologically stable on a stable or decreasing dose of steroids for at least 7 days prior to enrollment.
• Subjects must have a Lansky (\< 16 years) or Karnofsky (≥ 16 years) score of at least 50.
• Life expectancy greater than or equal to 12 weeks, in the investigator's opinion.
• Adequate hematologic, renal and hepatic function. Phase 2
Inclusion Criteria:
• Cohort Specific
Inclusion Criteria:
* Cohort 1: Subjects with NTRK fusion gene positive (NTRK+) advanced solid tumors (including primary CNS tumors), that are tropomyosin receptor kinase (TRK) TKI naïve;
* Cohort 2: subjects with NTRK+ advanced solid tumors (including primary CNS tumors), that are TRK TKI pre-treated;
* Cohort 3: subjects with advanced solid tumors with ROS1 gene fusions or other ROS1 aberrations (including amplifications and point mutations) with measurable disease.
• Subjects in Cohorts 1 and 2 must have prospectively confirmed measurable disease by BICR prior to enrollment. Key Exclusion Criteria (Phase 1 and Phase 2):
• Subjects with neuroblastoma with only bone marrow disease evaluable by bone marrow aspiration only.
• Major surgery within 14 days (2 weeks) of start of repotrectinib treatment. Central venous access (Broviac, Mediport, etc.) placement does not meet criteria for major surgery.
• Known active infections requiring ongoing treatment (bacterial, fungal, viral including HIV positivity).
• Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
• Any of the following cardiac criteria: * Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTc) \> 480 msec obtained from three ECGs, using the screening clinic ECG machine-derived QTc value * Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval \> 250 msec) * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval
• Peripheral neuropathy of CTCAE ≥grade 2.
• Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers.
• Any potential allergies to repotrectinib and/or its excipients.
DRUG: Oral repotrectinib (TPX-0005)
Locally Advanced Solid Tumors, Metastatic Solid Tumors, Lymphoma, Primary CNS Tumors, Breast - Female, Breast - Male, Colon, Kidney, Lung/Thoracic, Rectum, Soft Tissue, Thyroid, Urinary Bladder
ALK, ROS1, NTRK1-3, Primary CNS tumor, anaplastic large cell lymphoma, metastatic solid tumor, advanced solid tumor, sarcoma, infantile fibrosarcoma, glioblastoma, soft tissue schwannoma, solitary fibrous tumor, glioma, inflammatory myofibroblastic tumor, pediatric
Children’s Health
Cobimetinib in Refractory Langerhans Cell Histiocytosis (LCH), and Other Histiocytic Disorders (NACHO-COBI)
This is a research study of a drug called cobimetinib in children and adults diagnosed with Langerhans cell histiocytosis (LCH), and other histiocytic disorders that has returned or does not respond to treatment. Cobimetinib blocks activation of a protein called Mitogen-activated protein kinase (MEK) that is part of incorrect growth signals in histiocytosis cells. Four different groups of patients will be enrolled.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Erin Butler
All
Not specified
Phase 2
NCT04079179
STU-2021-0830
INCLUSION CRITERIA:
Age at study entry
• For Group 1: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment
• For Group 2: Participant may be at least 6 months of age at the time of enrollment
• For Group 3: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment
• For Group 4: Participant must be 21 years of age or older at the time of enrollment
• Participant must be able to take an enteral dose and formulation of medication. Study medication is only available as an oral suspension or tablet which may be taken by mouth or other enteral route such as nasogastric or gastric tube.
• Biopsy proven LCH -AND
• Failure of at least front-line therapy for LCH with evaluable disease. -OR
• Diagnosis of LCH-associated neurodegenerative disease with radiologic or clinical progression within the past 3 months. -OR
• Biopsy proven JXG, ECD, RDD, histiocytic sarcoma, or other histiocytic lesion (newly diagnosed or relapsed/refractory disease) with evaluable active disease. Performance Level: -Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50% for patients ≤ 16 years of age. Adequate Hematologic Function Defined as:
• ANC ≥ 0.75 x 10^9/L (unsupported/without growth factor stimulant)
• Platelet count ≥ 75 x 10^9/L (unsupported/without transfusion within the past 7 days).
• Patients with marrow disease must have platelet count of >/= 75 x 10^9/L (transfusion support allowed) and must not be refractory to platelet transfusions.
• Hemoglobin ≥ 8 g/dL (unsupported/without transfusion within the past 7 days)
• Patients with marrow disease must have hemoglobin ≥ 8 g/dL (transfusion support allowed). Adequate Renal Function Defined as:
• Calculated creatinine clearance (or radioisotope GFR) ≥ 70 mL/min/1.73m^2 or serum creatinine based on age/gender as follows: Maximum Serum Creatinine (mg/dL) Age 2 to < 6 years: Male 0.8 mg/d, Female 0.8; 6 to < 10 years: Male 1 mg/dL,Female 1; 10 to < 13 years: Male 1.2 mg/dL; Female 1.2; 13 to < 16 years: Male 1.5 mg/dL ; Female 1.4; ≥ 16 years: Male 1.7 mg/dL; Female 1.4; Adequate Liver Function Defined as:
• Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
• AST and ALT ≤ 3x ULN (≤ 5 x ULN for participants with liver involvement)
• Serum albumin ≥ 2 g/dL. For patients with liver disease caused by histiocytic disorder: • Patients may be enrolled with abnormal bilirubin, AST, ALT and albumin with documentation of histiocytic liver disease. Adequate Cardiac Function Defined as:
• Fractional shortening (FS) of ≥ 30% or ejection fraction of ≥ 50% by echocardiogram at baseline, as determined by echocardiography or multigated acquisition scan (MUGA) within 28 days prior to enrollment. Depending on institutional standard, either FS or LVEF is adequate for enrollment if only one value is measured; if both values are measured, then both values must meet criteria above Pregnancy/Birth Control
• Female patients of childbearing potential require a negative urine or serum pregnancy test for eligibility and again at database registration, if more than 2 weeks has elapsed.
• Female patients of childbearing potential must agree to follow the contraceptive requirements using two forms of effective contraceptive methods for the duration of the study treatment. Male patients with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) must agree to use two forms of effective methods of contraception (one of which must be a barrier method) during the treatment period and for at least 3 months after the last dose of the study drug to avoid pregnancy and/or potential adverse effects on a developing embryo. Agreement to true abstinence (not periodic abstinence or withdrawal method) is an acceptable method of birth control. EXCLUSION CRITERIA:
• Prior and Concomitant Use of Drugs with CYP3A4 inducing/inhibiting activity: Patient taking strong inducers or inhibitors of CYP3A4 within 14 days prior to study enrollment, including but not limited to the following: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John's wort.
• Prior Therapy Restrictions Completion of previous chemotherapy, immunotherapy, radiotherapy, or targeted therapy for LCH (or other histiocytic disorder) at least 28 days (except where specified below) prior to study enrollment, with resolution of all associated toxicity to ≤ Grade 1 prior to study enrollment (exception for alopecia and ototoxicity which do not need to be resolved ≤ Grade 1). Patients 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 enrollment. If after the required timeframe, the laboratory eligibility criteria are met, the patient is considered to have recovered adequately.
• Radiation therapy within the 28 days prior to enrollment.
• Any prior treatment with Cobimetinib.
• Treatment with a long-acting hematopoietic growth factor within 14 days prior to initiation of study drug or a short-acting hematopoietic growth factor within 7 days prior to enrollment.
• Treatment with hormonal therapy (except hormone replacement therapy or oral contraceptives), immunotherapy, biologic therapy, investigational therapy, or herbal cancer therapy within 28 days or < 5 half-lives, whichever is longer, prior to study enrollment.
• Treatment with high-dose chemotherapy and stem-cell rescue (autologous stem cell transplant) or allogeneic stem cell transplant within 90 days prior to enrollment. Anti-GVHD agents post-transplant: Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial.
• For patients with brain tumors (intracranial masses), use of anticoagulants within 7 days prior to enrollment.
• Corticosteroid therapy <0.5 mg/kg/day averaged during the month prior to study enrollment is permissible but must be discontinued fourteen (14) days prior to enrollment. Patients with documented brain lesions receiving corticosteroids for management of cerebral edema must be on a stable dose for fourteen (14) days prior to enrollment.
• Patient has received treatment with investigational therapy within 4 weeks prior to initiation of study drug.
• Patients taking anticoagulants or have a pre-existing bleeding disorder unrelated to histiocytic disease.
• Exclusions for other illness
• Other active malignancy or history of secondary malignancy.
• Refractory nausea and vomiting, malabsorption, external biliary shunt
• Infection: Patients who have a known active infection (excluding documented fungal infection of the nail beds) within 28 days prior to enrollment that has not completely resolved.
• Major surgical procedure or significant traumatic injury within 28 days prior to enrollment, or anticipation of need for major surgical procedure during the course of the study. Placement of a vascular access device or minor surgery is permitted within fourteen (14) days prior to study enrollment (provided that the wound has healed).
• History of significant bowel resection that would preclude adequate absorption or other significant malabsorptive disease.
• History of pneumonitis.
• Ophthalmologic considerations: Patients with known significant ophthalmologic conditions or known risk factors for retinal vein occlusion are not eligible. Specifically, patients with a history of retinal vein occlusion (RVO), retinal detachment, retinal pathology on ophthalmologic exam, retinopathy of prematurity, central serous chorioretinopathy (CSSCR), neovascular retinopathy, intraocular pressure > 21 mmHg, and predisposing factors to RVO (e.g., uncontrolled hypertension, diabetes, or hyperlipidemia, coagulopathy) will be excluded. Patients with longstanding and stable ophthalmologic findings secondary to existing conditions are eligible with appropriate written documentation and approval from Study Chair.
• History of solid organ transplantation: Patients who have received a prior solid organ transplantation are not eligible.
• Any other disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that in the opinion of the investigator contraindicates use of an investigational drug or places the patient at unacceptable risk from treatment complications.
• History of clinically significant cardiac dysfunction, including the following:
• Clinically significant cardiac arrhythmias including brady-arrhythmias and/or patients who require anti-arrhythmic therapy (with the exception of beta blockers or digoxin). Patients with controlled atrial fibrillation are not excluded.
• Unstable arrhythmia
• Unstable angina, or new-onset angina within 3 months prior to initiation of study treatment
• Symptomatic congestive heart failure, defined as New York Heart Association Class II or higher
• Myocardial infarction within 3 months prior to initiation of study treatment
• Known chronic human immunodeficiency virus (HIV).
• History of Grade ≥ 2 CNS hemorrhage or history of any CNS hemorrhage within 28 days of enrollment.
• Female patients who are pregnant or lactating. Pregnant or lactating women will not be entered on this study because there is no available information regarding human fetal or teratogenic toxicities.
• For Group 1: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment
• For Group 2: Participant may be at least 6 months of age at the time of enrollment
• For Group 3: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment
• For Group 4: Participant must be 21 years of age or older at the time of enrollment
• Participant must be able to take an enteral dose and formulation of medication. Study medication is only available as an oral suspension or tablet which may be taken by mouth or other enteral route such as nasogastric or gastric tube.
• Biopsy proven LCH -AND
• Failure of at least front-line therapy for LCH with evaluable disease. -OR
• Diagnosis of LCH-associated neurodegenerative disease with radiologic or clinical progression within the past 3 months. -OR
• Biopsy proven JXG, ECD, RDD, histiocytic sarcoma, or other histiocytic lesion (newly diagnosed or relapsed/refractory disease) with evaluable active disease. Performance Level: -Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50% for patients ≤ 16 years of age. Adequate Hematologic Function Defined as:
• ANC ≥ 0.75 x 10^9/L (unsupported/without growth factor stimulant)
• Platelet count ≥ 75 x 10^9/L (unsupported/without transfusion within the past 7 days).
• Patients with marrow disease must have platelet count of >/= 75 x 10^9/L (transfusion support allowed) and must not be refractory to platelet transfusions.
• Hemoglobin ≥ 8 g/dL (unsupported/without transfusion within the past 7 days)
• Patients with marrow disease must have hemoglobin ≥ 8 g/dL (transfusion support allowed). Adequate Renal Function Defined as:
• Calculated creatinine clearance (or radioisotope GFR) ≥ 70 mL/min/1.73m^2 or serum creatinine based on age/gender as follows: Maximum Serum Creatinine (mg/dL) Age 2 to < 6 years: Male 0.8 mg/d, Female 0.8; 6 to < 10 years: Male 1 mg/dL,Female 1; 10 to < 13 years: Male 1.2 mg/dL; Female 1.2; 13 to < 16 years: Male 1.5 mg/dL ; Female 1.4; ≥ 16 years: Male 1.7 mg/dL; Female 1.4; Adequate Liver Function Defined as:
• Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
• AST and ALT ≤ 3x ULN (≤ 5 x ULN for participants with liver involvement)
• Serum albumin ≥ 2 g/dL. For patients with liver disease caused by histiocytic disorder: • Patients may be enrolled with abnormal bilirubin, AST, ALT and albumin with documentation of histiocytic liver disease. Adequate Cardiac Function Defined as:
• Fractional shortening (FS) of ≥ 30% or ejection fraction of ≥ 50% by echocardiogram at baseline, as determined by echocardiography or multigated acquisition scan (MUGA) within 28 days prior to enrollment. Depending on institutional standard, either FS or LVEF is adequate for enrollment if only one value is measured; if both values are measured, then both values must meet criteria above Pregnancy/Birth Control
• Female patients of childbearing potential require a negative urine or serum pregnancy test for eligibility and again at database registration, if more than 2 weeks has elapsed.
• Female patients of childbearing potential must agree to follow the contraceptive requirements using two forms of effective contraceptive methods for the duration of the study treatment. Male patients with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) must agree to use two forms of effective methods of contraception (one of which must be a barrier method) during the treatment period and for at least 3 months after the last dose of the study drug to avoid pregnancy and/or potential adverse effects on a developing embryo. Agreement to true abstinence (not periodic abstinence or withdrawal method) is an acceptable method of birth control. EXCLUSION CRITERIA:
• Prior and Concomitant Use of Drugs with CYP3A4 inducing/inhibiting activity: Patient taking strong inducers or inhibitors of CYP3A4 within 14 days prior to study enrollment, including but not limited to the following: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John's wort.
• Prior Therapy Restrictions Completion of previous chemotherapy, immunotherapy, radiotherapy, or targeted therapy for LCH (or other histiocytic disorder) at least 28 days (except where specified below) prior to study enrollment, with resolution of all associated toxicity to ≤ Grade 1 prior to study enrollment (exception for alopecia and ototoxicity which do not need to be resolved ≤ Grade 1). Patients 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 enrollment. If after the required timeframe, the laboratory eligibility criteria are met, the patient is considered to have recovered adequately.
• Radiation therapy within the 28 days prior to enrollment.
• Any prior treatment with Cobimetinib.
• Treatment with a long-acting hematopoietic growth factor within 14 days prior to initiation of study drug or a short-acting hematopoietic growth factor within 7 days prior to enrollment.
• Treatment with hormonal therapy (except hormone replacement therapy or oral contraceptives), immunotherapy, biologic therapy, investigational therapy, or herbal cancer therapy within 28 days or < 5 half-lives, whichever is longer, prior to study enrollment.
• Treatment with high-dose chemotherapy and stem-cell rescue (autologous stem cell transplant) or allogeneic stem cell transplant within 90 days prior to enrollment. Anti-GVHD agents post-transplant: Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial.
• For patients with brain tumors (intracranial masses), use of anticoagulants within 7 days prior to enrollment.
• Corticosteroid therapy <0.5 mg/kg/day averaged during the month prior to study enrollment is permissible but must be discontinued fourteen (14) days prior to enrollment. Patients with documented brain lesions receiving corticosteroids for management of cerebral edema must be on a stable dose for fourteen (14) days prior to enrollment.
• Patient has received treatment with investigational therapy within 4 weeks prior to initiation of study drug.
• Patients taking anticoagulants or have a pre-existing bleeding disorder unrelated to histiocytic disease.
• Exclusions for other illness
• Other active malignancy or history of secondary malignancy.
• Refractory nausea and vomiting, malabsorption, external biliary shunt
• Infection: Patients who have a known active infection (excluding documented fungal infection of the nail beds) within 28 days prior to enrollment that has not completely resolved.
• Major surgical procedure or significant traumatic injury within 28 days prior to enrollment, or anticipation of need for major surgical procedure during the course of the study. Placement of a vascular access device or minor surgery is permitted within fourteen (14) days prior to study enrollment (provided that the wound has healed).
• History of significant bowel resection that would preclude adequate absorption or other significant malabsorptive disease.
• History of pneumonitis.
• Ophthalmologic considerations: Patients with known significant ophthalmologic conditions or known risk factors for retinal vein occlusion are not eligible. Specifically, patients with a history of retinal vein occlusion (RVO), retinal detachment, retinal pathology on ophthalmologic exam, retinopathy of prematurity, central serous chorioretinopathy (CSSCR), neovascular retinopathy, intraocular pressure > 21 mmHg, and predisposing factors to RVO (e.g., uncontrolled hypertension, diabetes, or hyperlipidemia, coagulopathy) will be excluded. Patients with longstanding and stable ophthalmologic findings secondary to existing conditions are eligible with appropriate written documentation and approval from Study Chair.
• History of solid organ transplantation: Patients who have received a prior solid organ transplantation are not eligible.
• Any other disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that in the opinion of the investigator contraindicates use of an investigational drug or places the patient at unacceptable risk from treatment complications.
• History of clinically significant cardiac dysfunction, including the following:
• Clinically significant cardiac arrhythmias including brady-arrhythmias and/or patients who require anti-arrhythmic therapy (with the exception of beta blockers or digoxin). Patients with controlled atrial fibrillation are not excluded.
• Unstable arrhythmia
• Unstable angina, or new-onset angina within 3 months prior to initiation of study treatment
• Symptomatic congestive heart failure, defined as New York Heart Association Class II or higher
• Myocardial infarction within 3 months prior to initiation of study treatment
• Known chronic human immunodeficiency virus (HIV).
• History of Grade ≥ 2 CNS hemorrhage or history of any CNS hemorrhage within 28 days of enrollment.
• Female patients who are pregnant or lactating. Pregnant or lactating women will not be entered on this study because there is no available information regarding human fetal or teratogenic toxicities.
Drug: Cobimetinib
Langerhan's Cell Histiocytosis, Juvenile Xanthogranuloma, Erdheim-Chester Disease, Rosai Dorfman Disease, Neuro-Degenerative Disease, Histiocytic Sarcoma, Histiocytic Disorders, Malignant, Bones and Joints, Brain and Nervous System, Liver, Lung/Thoracic, Other Hematopoietic
Cobimetinib, Langerhans Cell Histiocytosis (LCH)
Children’s Health
First in Human Study of Ziftomenib in Relapsed or Refractory Acute Myeloid Leukemia
In this trial, ziftomenib, a menin-MLL(KMT2A) inhibitor, will be tested in patients for the first time. The trial includes a Main Study and four sub-studies. In the Main Study (including Phase 1a, Phase 1b, and Phase 2 portions), ziftomenib will be evaluated in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML). The main study has completed enrollment. In Sub-studies 1 and 2, the effects of taking ziftomenib and other common drugs at the same time will be investigated in AML patients. In Sub-study 3, ziftomenib will be evaluated in patients with R/R acute lymphoblastic leukemia (ALL). In Sub-study 4, ziftomenib will be evaluated in patients with R/R AML with certain genetic mutations.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
ALL
18 Years and over
PHASE1
NCT04067336
STU-2021-0258
Key
• Phase 1b: * Patients with a documented lysine\[K\]-specific methyltransferase 2-rearrangement (KMT2A-r), or * Patients with a documented nucleophosmin 1 mutation (NPM1-m)
• Phase 2: * Patients with a documented nucleophosmin 1 mutation (NPM1-m)
• Sub-studies: * Sub-studies 1 and 2: Patients with R/R AML with NPM1-m or other mutations associated with MEIS1 overexpression. * Sub-study 3: Patients with R/R Acute Lymphoblastic Leukemia (ALL) with KMT2A-r. * Sub-study 4: Patients with R/R AML with mutations associated with MEIS1 overexpression.
• ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, and a life expectancy of at least 2 months.
• Adequate liver and kidney function according to protocol requirements.
• Peripheral white blood cell (WBC) counts ≤ 30,000/μL. Patients may receive hydroxyurea to control and maintain white blood cell count prior to enrollment.
• Women of childbearing potential must be willing to use a highly effective method of contraception throughout the study and for at least 187 days after the last dose of study treatment.
• Males with female partners of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 97 days after the last dose of study treatment. Key
• Diagnosis of acute promyelocytic leukemia.
• Diagnosis of chronic myelogenous leukemia in blast crisis.
• Donor lymphocyte infusion \< 30 days prior to study entry.
• Clinically active central nervous system (CNS) leukemia.
• Undergone HSCT and have not had adequate hematologic recovery.
• Receiving immunosuppressive therapy post HSCT within 2 weeks of Cycle 1 Day 1.
• Grade ≥ 2 active graft-versus-host disease (GVHD), moderate or severe limited chronic GVHD, or extensive chronic GVHD of any severity.
• Received chemotherapy immunotherapy, radiotherapy, or any ancillary therapy that is considered to be investigational (i.e., used for non-approved indications(s) and in the context of a research investigation) \< 14 days prior to the first dose of ziftomenib or within 5 drug half-lives prior to the first dose of study drug.
• Not recovered to \< Grade 2 (National Cancer Institute Common Terminology Criteria for Adverse Events v5.0) from all acute toxicities or deemed back to a stable baseline.
• Treatment with concomitant drugs that are strong inhibitors or inducers of cytochrome P450-isozyme 3A4 (CYP3A4), as follows: * Phase 1a, 1b, 2, and sub-studies 3 and 4: with the exception of antibiotics, antifungals, and antivirals that are used as standard of care or to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the patient. * Sub-studies 1 and 2: No exceptions will be allowed except for the use of moderate CYP3A4 antifungal prophylaxis such as fluconazole or isavuconazole which is at steady state on Cycle 1 Day 1 and will continue through the completion of PKs on Cycle 1 Day 15 (for sub-study 1) or Cycle 1 Day 18 (for sub-study 2).
• Detectable viral load for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen indicative of active infection. Patients with controlled disease will not be excluded from study enrollment.
• Pre-existing disorder predisposing the patient to a serious or life-threatening infection (e.g. cystic fibrosis, congenital or acquired immunodeficiency, bleeding disorder, or cytopenias not related to AML).
• Active uncontrolled acute or chronic systemic fungal, bacterial, viral, or other infection.
• Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension or arrhythmia, history of cerebrovascular accident including transient ischemic attack within the past 6 months, congestive heart failure (NYHA Class III or IV) related to primary cardiac disease, ischemic or severe valvular heart disease, or a myocardial infarction within 6 months prior to the first dose of study treatment.
• Mean QTcF \>480 ms on triplicate ECG.
• Major surgery within 4 weeks prior to the first dose of study treatment.
• Women who are pregnant or lactating. All female patients with reproductive potential must have a negative serum pregnancy test within 72 hours prior to starting treatment.
• For sub-studies 1 and 2: Any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade, or other products containing grapefruit or Seville oranges within 7 days of the first administration of ziftomenib until the end of Cycle 1.
• For sub-studies 1 and 2: Moderate (Child-Pugh class B) or severe (Child-Pugh class C) hepatic impairment.
Inclusion Criteria:
Patients with refractory or relapsed AML defined as the reappearance of ≥ 5% blasts in the bone marrow and who have also failed or are ineligible for any approved standard of care therapies, including HSCT.
• Phase 1b: * Patients with a documented lysine\[K\]-specific methyltransferase 2-rearrangement (KMT2A-r), or * Patients with a documented nucleophosmin 1 mutation (NPM1-m)
• Phase 2: * Patients with a documented nucleophosmin 1 mutation (NPM1-m)
• Sub-studies: * Sub-studies 1 and 2: Patients with R/R AML with NPM1-m or other mutations associated with MEIS1 overexpression. * Sub-study 3: Patients with R/R Acute Lymphoblastic Leukemia (ALL) with KMT2A-r. * Sub-study 4: Patients with R/R AML with mutations associated with MEIS1 overexpression.
• ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, and a life expectancy of at least 2 months.
• Adequate liver and kidney function according to protocol requirements.
• Peripheral white blood cell (WBC) counts ≤ 30,000/μL. Patients may receive hydroxyurea to control and maintain white blood cell count prior to enrollment.
• Women of childbearing potential must be willing to use a highly effective method of contraception throughout the study and for at least 187 days after the last dose of study treatment.
• Males with female partners of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 97 days after the last dose of study treatment. Key
Exclusion Criteria:
• Diagnosis of acute promyelocytic leukemia.
• Diagnosis of chronic myelogenous leukemia in blast crisis.
• Donor lymphocyte infusion \< 30 days prior to study entry.
• Clinically active central nervous system (CNS) leukemia.
• Undergone HSCT and have not had adequate hematologic recovery.
• Receiving immunosuppressive therapy post HSCT within 2 weeks of Cycle 1 Day 1.
• Grade ≥ 2 active graft-versus-host disease (GVHD), moderate or severe limited chronic GVHD, or extensive chronic GVHD of any severity.
• Received chemotherapy immunotherapy, radiotherapy, or any ancillary therapy that is considered to be investigational (i.e., used for non-approved indications(s) and in the context of a research investigation) \< 14 days prior to the first dose of ziftomenib or within 5 drug half-lives prior to the first dose of study drug.
• Not recovered to \< Grade 2 (National Cancer Institute Common Terminology Criteria for Adverse Events v5.0) from all acute toxicities or deemed back to a stable baseline.
• Treatment with concomitant drugs that are strong inhibitors or inducers of cytochrome P450-isozyme 3A4 (CYP3A4), as follows: * Phase 1a, 1b, 2, and sub-studies 3 and 4: with the exception of antibiotics, antifungals, and antivirals that are used as standard of care or to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the patient. * Sub-studies 1 and 2: No exceptions will be allowed except for the use of moderate CYP3A4 antifungal prophylaxis such as fluconazole or isavuconazole which is at steady state on Cycle 1 Day 1 and will continue through the completion of PKs on Cycle 1 Day 15 (for sub-study 1) or Cycle 1 Day 18 (for sub-study 2).
• Detectable viral load for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen indicative of active infection. Patients with controlled disease will not be excluded from study enrollment.
• Pre-existing disorder predisposing the patient to a serious or life-threatening infection (e.g. cystic fibrosis, congenital or acquired immunodeficiency, bleeding disorder, or cytopenias not related to AML).
• Active uncontrolled acute or chronic systemic fungal, bacterial, viral, or other infection.
• Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension or arrhythmia, history of cerebrovascular accident including transient ischemic attack within the past 6 months, congestive heart failure (NYHA Class III or IV) related to primary cardiac disease, ischemic or severe valvular heart disease, or a myocardial infarction within 6 months prior to the first dose of study treatment.
• Mean QTcF \>480 ms on triplicate ECG.
• Major surgery within 4 weeks prior to the first dose of study treatment.
• Women who are pregnant or lactating. All female patients with reproductive potential must have a negative serum pregnancy test within 72 hours prior to starting treatment.
• For sub-studies 1 and 2: Any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade, or other products containing grapefruit or Seville oranges within 7 days of the first administration of ziftomenib until the end of Cycle 1.
• For sub-studies 1 and 2: Moderate (Child-Pugh class B) or severe (Child-Pugh class C) hepatic impairment.
DRUG: Ziftomenib, DRUG: Midazolam, DRUG: Itraconazole
Advanced Malignant Neoplasm, Acute Myeloid Leukemia, Mixed Lineage Leukemia, Mixed Lineage Acute Leukemia, Acute Leukemia of Ambiguous Lineage, Mixed Phenotype Acute Leukemia, Acute Lymphoblastic Leukemia, Myeloid and Monocytic Leukemia
AML, Hematological malignancy, KMT2A, NPM1, Menin, Leukemia, Acute Leukemia, ALL, MLL, Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, MEIS1
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
Project: Every Child for Younger Patients With Cancer
This study gathers health information for the Project: Every Child for younger patients with cancer. Gathering health information over time from younger patients with cancer may help doctors find better methods of treatment and on-going care.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Laura Klesse
ALL
up to 25 Years old
N/A
NCT02402244
STU 112015-029
Inclusion Criteria:
* Enrollment must occur within 6 months of initial disease presentation OR within 6 months of refractory disease, disease progression, disease recurrence, second or secondary malignancy, or post-mortem
* Patients previously enrolled on ACCRN07 are eligible to enroll on Tracking Outcome, Registry and Future Contact components of APEC14B1 any time after they reach age of majority
* Patients with a known or suspected neoplasm that occurs in the pediatric, adolescent or young adult populations are eligible for enrollment as follows:
* All cancer cases with an International Classification of Diseases for Oncology (ICD-O) histologic behavior code of one "1" (borderline), two "2" (carcinoma in situ) or three "3" (malignant)
* All neoplastic lesions of the central nervous system regardless of behavior, i.e., benign, borderline or malignant
* All neoplastic lesions of the kidney regardless of behavior, i.e., benign, borderline or malignant
* The following other benign/borderline conditions:
* Mesoblastic nephroma
* Teratomas (mature and immature types)
* Myeloproliferative diseases including transient myeloproliferative disease
* Langerhans cell histiocytosis
* Lymphoproliferative diseases
* Desmoid tumors
* Gonadal stromal cell tumors
* Neuroendocrine tumors including pheochromocytoma
* Melanocytic tumors, except clearly benign nevi
* Ganglioneuromas
* Subjects must be =\< 25 years of age at time of original diagnosis, except for patients who are being screened specifically for eligibility onto a COG (or COG participating National Clinical Trials Network \[NCTN\]) therapeutic study, for which there is a higher upper age limit
* All patients or their parents or legally authorized representatives must sign a written informed consent and agree to participate in at least one component of the study; parents will be asked to sign a separate consent for their own biospecimen submission
* If patients or their parents or legally authorized representatives have not signed the Part A subject consent form at the time of a diagnostic bone marrow procedure, it is recommended that they initially provide consent for drawing extra bone marrow using the Consent for Collection of Additional Bone Marrow; consent using the Part A subject consent form must be provided prior to any other procedures for eligibility screening or banking under APEC14B1 OTHER: Cytology Specimen Collection Procedure, OTHER: Medical Chart Review
Adrenal Gland Pheochromocytoma, Carcinoma In Situ, Central Nervous System Neoplasm, Childhood Immature Teratoma, Childhood Kidney Neoplasm, Childhood Langerhans Cell Histiocytosis, Childhood Mature Teratoma, Congenital Mesoblastic Nephroma, Desmoid Fibromatosis, Ganglioneuroma, Lymphoproliferative Disorder, Malignant Neoplasm, Malignant Solid Neoplasm, Melanocytic Neoplasm, Myeloproliferative Neoplasm, Neoplasm of Uncertain Malignant Potential, Neuroendocrine Neoplasm, Stromal 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, Rectum, Sarcoma, Small Intestine, Soft Tissue, Stomach, Throat, Thyroid, Unknown Sites, Urinary Bladder, Uterine (Endometrial), Vulva
Children’s Health
Long-Term Follow-Up of Patients Who Have Participated in Children's Oncology Group Studies
This clinical trial keeps track of and collects follow-up information from patients who are currently enrolled on or have participated in a Children's Oncology Group study. Developing a way to keep track of patients who have participated in Children's Oncology Group studies may allow doctors learn more about the long-term effects of cancer treatment and help them reduce problems related to treatment and improve patient quality of life.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Laura Klesse
ALL
Not specified
N/A
NCT00736749
STU 072011-021
Inclusion Criteria:
* The patient must reside in the U.S. on the date of enrollment to ALTE05N1
* 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: Assessment of Therapy Complications, OTHER: Questionnaire Administration
Hematopoietic Cell Transplantation Recipient, Leukemia, Solid Tumor, Anus, Bones and Joints, Brain and Nervous System, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, 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, Small Intestine, Soft Tissue, Stomach, Thyroid, Unknown Sites
Children’s Health
A Study of Pembrolizumab (MK-3475) in Pediatric Participants With an Advanced Solid Tumor or Lymphoma (MK-3475-051/KEYNOTE-051)
This is a two-part study of pembrolizumab (MK-3475) in pediatric participants who have any of the following types of cancer: - advanced melanoma (6 months to <18 years of age), - advanced, relapsed or refractory programmed death-ligand 1 (PD-L1)-positive malignant solid tumor or other lymphoma (6 months to <18 years of age), - relapsed or refractory classical Hodgkin lymphoma (rrcHL) (3 years to <18 years of age), or - advanced relapsed or refractory microsatellite-instability-high (MSI-H) solid tumors (6 months to <18 years of age). Part 1 will find the maximum tolerated dose (MTD)/maximum administered dose (MAD), confirm the dose, and find the recommended Phase 2 dose (RP2D) for pembrolizumab therapy. Part 2 will further evaluate the safety and efficacy at the pediatric RP2D. The primary hypothesis of this study is that intravenous (IV) administration of pembrolizumab to children with either advanced melanoma; a PD-L1 positive advanced, relapsed or refractory solid tumor or other lymphoma; advanced, relapsed or refractory MSI-H solid tumor; or rrcHL, will result in an Objective Response Rate (ORR) greater than 10% for at least one of these types of cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tanya Watt
All
6 Months to 17 Years old
Phase 1/Phase 2
NCT02332668
STU 052016-090
Inclusion Criteria:
• Between 6 months and <18 years of age (or between 3 years and <18 years of age for rrcHL participants) on day of signing informed consent/assent (the first 3 participants dosed in Part 1 are to be ≥ 6 years of age)
• Histologically- or cytologically-documented, locally-advanced, or metastatic solid malignancy or lymphoma that is incurable and has failed prior standard therapy, or for which no standard therapy exists, or for which no standard therapy is considered appropriate
• Any number of prior treatment regimens
• Tissue (or lymph node biopsy for rrcHL participants) available from an archival tissue sample or, if appropriate, a newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
• Advanced melanoma or PD-L1-positive advanced, relapsed, or refractory solid tumor or lymphoma
• Measurable disease based on RECIST 1.1 (Or based on IWG [Cheson, 2007] [i.e., measurement must be >15 mm in longest diameter or >10 mm in short axis] for rrcHL participants)
• Participants with neuroblastoma with only metaiodobenzylguanidine (MIBG)-positive evaluable disease may be enrolled
• Lansky Play Scale ≥50 for participants from 6 months up to and including 16 years of age; or Karnofsky score ≥50 for participants >16 years of age
• Adequate organ function
• Female participants of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication
• Female participants of childbearing potential must be willing to use 2 methods of contraception or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication
• Male participants of reproductive potential must agree to use an adequate method of contraception starting with the first dose of study medication through 120 days after the last dose of study medication
Exclusion Criteria:
• Currently participating and receiving study therapy in, or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the date of allocation/randomization
• Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the date of allocation/randomization
• Prior systemic anti-cancer therapy including investigational agent within 2 weeks prior to study Day 1 or not recovered from adverse events due to a previously administered agent
• Prior radiotherapy within 2 weeks of start of study treatment
• Known additional malignancy that is progressing or requires active treatment with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (eg, breast carcinoma, cervical carcinoma in situ) with potentially curative therapy, or in situ cervical cancer
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Tumor(s) involving the brain stem
• Severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients
• Active autoimmune disease that has required systemic treatment in past 2 years; replacement therapy (such as thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is acceptable
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Active infection requiring systemic therapy
• Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial through 120 days after the last dose of study medication
• Prior therapy with an anti-programmed cell death (PD)-1, anti-PD-ligand 1 (anti-PD-L1), anti-PD-L2 agent, or any agent directed to another stimulatory or inhibitory T-cell receptor (eg, cytotoxic lymphocyte associated protein-4 [CTLA-4], OX-40, CD137)
• Human immunodeficiency virus (HIV)
• Hepatitis B or C
• Known history of active tuberculosis (TB; Bacillus tuberculosis)
• Received a live vaccine within 30 days of planned start of study medication
• Has undergone solid organ transplant at any time, or prior allogeneic hematopoietic stem cell transplantation within the last 5 years. (Participants who have had an allogeneic hematopoietic transplant >5 years ago are eligible as long as there are no symptoms of Graft Versus Host Disease [GVHD].)
• History or current evidence of any condition, therapy, or laboratory abnormality, or known severe hypersensitivity to any component or analog of the trial treatment, that might confound the results of the trial, or interfere with the participant's participation for the full duration of the study
• Known psychiatric or substance abuse disorders that would interfere with the requirements of the study
Biological: Pembrolizumab
Melanoma, Lymphoma, Solid Tumor, Classical Hodgkin Lymphoma, Microsatellite-instability-high Solid Tumor, Melanoma, skin, Other
PD1, PD-1, PDL1, PD-L1, cHL, MSI-H
Children’s Health
Safety Study of Cord Blood Units for Stem Cell Transplants
Background: - Cord blood is blood that is taken from the umbilical cord and placenta of healthy newborns after childbirth. The cord blood collected from a baby is called a cord blood unit. Cord blood units are stored frozen in public cord blood banks. About 10,000 cord blood transplants have been performed in children and adults for blood cancers and other diseases in the world. These transplants have helped save lives and improve treatments. However, not all available units of cord blood have been collected, stored, and licensed according to specific government requirements. These unlicensed units can still be used in transplant, but they can only be given as part of specific research studies. This study will evaluate the safety of giving these unlicensed units by recording any problems that may occur during and after giving the cord blood. Objectives: - To test the safety and effectiveness of unlicensed cord blood units in people who need stem cell transplants. Eligibility: - Individuals who are scheduled to have a stem cell transplant. Design: - Participants will be screened with a medical history and physical exam. - Participants will receive the cord blood unit as part of their stem cell transplant procedure. The transplant will be performed according to the current standard of care for the procedure. - After the transplant, participants will be monitored for up to 1 year. Any problems or side effects from the transplant will be treated as necessary. All outcomes will be reported to the National Cord Blood Program and to the Center for International Blood and Marrow Transplant.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Gevel.Jackson@childrens.com
Victor Aquino
All
Not specified
Phase 2
NCT01861093
STU 082013-056
• INCLUSION CRITERIA:
• Patients of any age or either gender with indications for receipt of investigational HPC-CORD BLOOD who are participating in an NIH-IRB approved clinical trial for unrelated hematopoietic stem cell transplantation.
• Signed informed consent (and assent when applicable). EXCLUSION CRITERIA:
• Patients who are receiving licensed CB products (only)
• Patients who are receiving unlicensed CB products from other CB banks (i.e. NMDP)
Procedure: Cord Blood Units
Aplastic Anemia, Leukemia, Myelodysplastic Syndrome (MDS), Lymphoma, Unknown Sites
Unrelated Hematopoietic Stem Cell Transplantation, Cryopreserved Cord Blood Units, National Cord Blood Program
Children’s Health
Phase 1 Dose-escalating Study of MM-398 (Irinotecan Sucrosofate Liposome Injection) Plus Intravenous Cyclophosphamide in Recurrent or Refractory Pediatric Solid Tumors
This is a Phase 1 study of the combination of two drugs: MM-398 and Cyclophosphamide. The goal is to find the highest dose of MM-398 that can be given safely when it is used together with the chemotherapy drug Cyclophosphamide.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Patrick Leavey
All
12 Months to 20 Years old
Phase 1
NCT02013336
STU 092013-007
Inclusion Criteria:
• Histologically or cytologically-confirmed Ewing sarcoma, rhabdomyosarcoma, neuroblastoma, or osteosarcoma
• Disease progression after prior therapy in locally advanced or metastatic setting
• Measurable or evaluable disease based on the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria
• Age 12 months to <21 years
• Adequate bone marrow reserves, hepatic function, and renal function
• Recovered from effects of any prior surgery or cancer therapy
• Patients 18 years or older will provide written consent. A parent or legal guardian of a patient <18 years of age will provide informed consent and patients 11 to 18 years of age will provide written assent or as per participating institutional policy.
Exclusion Criteria:
• Clinically significant gastrointestinal disorders
• NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure
• Active infection or unexplained fever
• Known hypersensitivity to any of the components of MM-398 or other liposomal products
• Recent Investigational therapy
• Pregnant or breast feeding; females of child-bearing potential must test negative for pregnancy at the time of enrollment
Drug: MM-398 (Irinotecan Sucrosofate Liposome Injection) plus cyclophosphamide
Recurrent or Refractory Solid Tumors, Ewing Sarcoma, Rhabdomyosarcoma, Neuroblastoma, Osteosarcoma, Anus, Bones and Joints, Brain and Nervous System, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Eye and Orbit, Gall Bladder, Head and Neck, Hodgkins Lymphoma, Kaposis sarcoma, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Mycosis Fungoides, Nose, 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, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva
pediatric, MM-398, cyclophosphamide, irinotecan
Children’s Health