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22 Study Matches
Vincristine Pharmacokinetics in Infants
This pilot trial compares drug exposure levels using a new method for dosing vincristine in infants and young children compared to the standard dosing method based on body surface area (BSA) in older children. Vincristine is an anticancer drug used to a variety of childhood cancers. The doses anticancer drugs in children must be adjusted based on the size of the child because children vary significantly in size (height, weight, and BSA) and ability to metabolize drugs from infancy to adolescence. The dose of most anticancer drugs is adjusted to BSA, which is calculated from a patient's weight and height. However, infants and young children have more severe side effects if the BSA is used to calculate their dose, so new dosing models have to be made to safely give anticancer drugs to the youngest patients. This new method uses a BSA-banded approach to determine the dose. Collecting blood samples before and after a dose of the drug will help researchers determine whether this new vincristine dosing method results in equivalent drug levels in the blood over time in infants and young children compared to older children.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Laura Klesse
13954
All
up to 12 Years old
Early Phase 1
NCT05359237
STU-2022-1175
Inclusion Criteria:
• Patients must be =< 12 years of age at the time of study enrollment. Patients will be stratified into 4 age groups:
• 0 to 6 months
• 6 months and 1 day to 12 months
• 12 months and 1 day to 36 months
• 36 months and 1 day to 12 years
• Newly diagnosed and relapsed cancer diagnosis that is being treated with vinCRIStine at the 1.5 mg/m^2 dose level
• Any disease status
• Patients must have a Lansky performance status of 50 or higher
• Patients must be receiving a treatment regimen that includes 1.5 mg/m^2 vinCRIStine (maximum dose 2 mg)
• Patients with a BSA < 0.6 m^2 must be dosed according to the Children's Oncology Group (COG) BSA-banded infant dosing table for the 1.5mg/m2 dose level for vinCRIStine
• Note: Patients can be studied after any dose of vinCRIStine
• Patients who are NOT enrolled on a COG clinical trial and who have a BSA < 0.6 m^2 and who are being dosed according to another infant dosing method (e.g., the 30-Rule) can receive a dose of vinCRIStine from the infant dosing table for the pharmacokinetic study. These patients will NOT be part of the Dose Modification Assessment
• Patients with a seizure disorder may be enrolled if on allowable anticonvulsants and well controlled as evidenced by no increase in seizure frequency in the prior 7 days
• Nervous system toxicities (Common Terminology Criteria for Adverse Events [CTCAE]) version (v)5 resulting from prior therapy must be grade =< 2
• Central venous access device in place (e.g., percutaneous indwelling central catheter [PICC], port, Broviac) or scheduled to be placed prior to the dose of vinCRIStine and that can be used for pharmacokinetic (PK) sampling
• VinCRIStine may be given as an outpatient, as long as all sample time points can be collected, which will require return for hour 24 sampling
Exclusion Criteria:
• Azoles antifungals and macrolide antibiotics: Patients who are currently receiving an azole or macrolide (e.g., fluconazole, isavuconazole, itraconazole, posaconazole, voriconazole, ketoconazole, eryromycin, clarithromycin, azithromycin, roxithromycin, or telithromycin) are not eligible
• CYP3A4/5 inducers/inhibitors: Patients receiving any medications or substances that are considered moderate or strong inhibitors or inducers of CYP3A4/5 are not eligible. Moderate or strong inducers or inhibitors of CYP3A4/5 should be avoided from 14 days prior to enrollment to the end of the study.
• Note the following are allowed:
• Dexamethasone for CNS tumors or metastases, on a stable dose
• Aprepitant for management of nausea and vomiting
• Anticonvulsants: Patients receiving moderate or strong CYP3A4/5 enzyme inducing anticonvulsants are not eligible.
• Patients with Charcot-Marie-Tooth disease
• A baseline neurological disorder with manifestations that overlap with vinCRIStine-associated neurotoxicities
• Patients being treated on a Children Oncology Group (COG) clinical trial, that does not use the infant dosing tables for vinCRIStine are not eligible for this study.
• Patients receiving a modified dose (< 1.5 mg/m^2) of vinCRIStine due to prior toxicity
• Patients who in the opinion of the investigator may not be able to comply with the sampling requirements of the study
Procedure: Biospecimen Collection, Drug: Vincristine
Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm, Brain and Nervous System, Bones and Joints, Kidney, Hodgkins Lymphoma, Lymphoid Leukemia, Non-Hodgkins Lymphoma, Soft Tissue
Children’s Health
Study of the Adverse Events and Change in Disease State of Pediatric Participants (and Young Adults Between the Ages of 18-25) With Relapsed/Refractory Aggressive Mature B-cell Neoplasms Receiving Subcutaneous (SC) Injections of Epcoritamab
The most common types of mature B-cell lymphomas (MBLs) in children are Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). Initial treatment cures 90% - 95% of children with these malignancies, leaving a very small population of relapsed/refractory disease with a poor prognosis. The purpose of this study is to assess the safety and tolerability of epcoritamab in pediatric participants with relapsed/refractory aggressive mature B-cell neoplasms and young adult participants with Burkitt's or Burkitt-like lymphoma/leukemia. Adverse events and change in disease activity will be assessed. Epcoritamab is an investigational drug being developed for the treatment of relapsed/refractory aggressive mature B-cell neoplasms. Participants will receive subcutaneous (SC) of epcoritamab. Approximately 15 pediatric participants with a diagnosis of relapsed/refractory aggressive mature B-cell neoplasms and and young adult participants, ages of 18-25, with a diagnosis of Burkitt's or Burkitt-like lymphoma/leukemia will be enrolled at 50 sites globally. Participants will receive subcutaneous epcoritamab in 28-day cycles. Participants will be followed for a minimum of 3 years after enrollment. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
67555
All
1 Year to 25 Years old
Phase 1
NCT05206357
STU-2022-1118
Inclusion Criteria:
• Participants >= 1 and < 18 years old at time of primary diagnosis with Burkitt's or Burkitt-like lymphoma/leukemia, diffuse large B-cell lymphoma (DLBCL), or other aggressive mature (CD20+) B-cell lymphomas. Participants up to 25 years of age with Burkitt's or Burkitt-like lymphoma/leukemia are also eligible.
• Disease pathologically confirmed (tumor tissue) by local testing.
• Relapsed or primary refractory disease meeting any of the following criteria:
• Progressive disease at any time during second-line chemoimmunotherapy (CIT).
• Best response of stable disease (SD) after a minimum of 2 cycles of second-line CIT.
• Best response of partial response (PR) after a minimum of 3 cycles of second-line CIT.
• Complete Response (CR) after a minimum of 3 cycles of second-line CIT therapy but unfit or ineligible for consolidation with cell therapy.
• Not in CR and unable to initiate or tolerate (i.e., must discontinue) second-line CIT.
• Have received cell therapy (allogeneic or autologous transplant or chimeric antigen receptor T-cell (CAR-T) therapy) as consolidation but have not obtained or maintained a CR.
• Recovery from toxic effects of prior chemoimmunotherapy.
• Performance status by Lansky (< 16 years old at evaluation) or Karnofsky (>= 16 years old at evaluation) score >= 50 or Eastern Cooperative Oncology Group (ECOG) score <= 2 .
• Adequate bone marrow, hepatic, and renal function.
Exclusion Criteria:
• Known central nervous system (CNS) involvement by lymphoma at screening as confirmed by screening magnetic resonance imaging (MRI)/computed tomography (CT)/positron emission tomography (PET) brain scans (participants with evidence of CNS disease only in the cerebrospinal fluid (CSF) will be eligible).
• Other malignancy requiring therapy.
• Currently receiving anti-cancer therapy, including chemotherapy (excluding intrathecal therapy), radiotherapy, small molecules, monoclonal antibodies, cell therapy, or other investigational agents.
Drug: Epcoritamab
Lymphoma, Non-hodgkin Lymphoma
Non-hodgkin Lymphoma, ABBV-GMAB-3013, Epcoritamab, Burkitt's or Burkitt-like Lymphoma/Leukemia, Diffuse Large B-cell Lymphoma, Aggressive Mature (CD20+) B-cell Lymphoma, Cancer, Relapsed/Refractory Aggressive Mature B-cell Neoplasms
Children’s Health
Venetoclax in Children With Relapsed Acute Myeloid Leukemia (AML)
A study to evaluate if the randomized addition of venetoclax to a chemotherapy backbone (fludarabine/cytarabine/gemtuzumab ozogamicin [GO]) improves survival of children/adolescents/young adults with acute myeloid leukemia (AML) in 1st relapse who are unable to receive additional anthracyclines, or in 2nd relapse.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kathleen Ludwig
114894
All
29 Days to 21 Years old
Phase 3
NCT05183035
STU-2022-0725
Inclusion Criteria
• Participants must have enrolled on APAL2020SC, NCT Number: NCT04726241 prior to enrollment on ITCC-101/APAL2020D. (This is only applicable for participants in USA/Canada/Australia/New Zealand sites/LLS territory).
• Participants must be ≥ 29 days of age and ≤ 21 years of age at enrollment.
• Participants must have one of the following:
• Children, adolescents, and young adults with acute myeloid leukemia without FLT3/internal tandem duplication (ITD) mutation in:
• Second relapse, who are sufficiently fit to undergo another round of intensive chemotherapy
• First relapse who per investigator discretion cannot tolerate additional anthracycline containing chemotherapy.
• Participants must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2 (≥ 50% Lansky or Karnofsky score)
• Participants must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to start of protocol treatment:
• Cytotoxic chemotherapy: Must not have received cytotoxic chemotherapy within 14 days prior to start of protocol treatment, except for corticosteroids, low dose cytarabine or hydroxyurea that can be given up to 24 hours prior to start of protocol treatment.
• Intrathecal cytotoxic therapy: No wash-out time is required for participants having received any combination of intrathecal cytarabine, methotrexate, and/or hydrocortisone.
• Antibodies: ≥ 21 days must have elapsed from infusion of last dose of an antibody-drug conjugate before start of protocol treatment. For unmodified antibodies or T cell engaging antibodies, 2 half-lives must have elapsed before start of protocol treatment. Any toxicity related to prior antibody therapy must be recovered to Grade ≤ 1.
• Interleukins, Interferons and Cytokines (other than Hematopoietic Growth Factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than Hematopoietic Growth Factors) before start of protocol treatment.
• Hematopoietic growth factors: ≥ 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or ≥7 days for short-acting growth factor before start of protocol treatment.
• Radiation therapy (RT) (before start of protocol treatment):
• ≥ 14 days have elapsed for local palliative RT (small port);
• ≥ 84 days must have elapsed if prior craniospinal RT or if ≥ 50% radiation of pelvis;
• ≥ 42 days must have elapsed if other substantial bone marrow (BM) radiation.
• Stem Cell Infusions (before start of protocol treatment):
• ≥ 84 days since allogeneic (non-autologous) bone marrow or stem cell transplant (with or without total body irradiation [TBI]) or boost infusion (any stem cell product; not including donor lymphocyte infusion [DLI])
• No evidence of active graft versus host disease (GVHD).
• Participants who are receiving cyclosporine, tacrolimus or other agents to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial. Participants must be off medications to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant for at least 14 days prior to enrollment.
• Cellular Therapy: ≥ 42 days after the completion of donor lymphocyte infusion (DLI) or any type of cellular therapy (e.g., modified T cells, natural killer [NK] cells, dendritic cells, etc.) before start of protocol treatment.
• Participants with prior exposure to venetoclax are eligible in this trial
• Adequate organ function:
• Adequate Renal Function defined as:
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 60ml/min/1.73 m^2, or
• Normal serum creatinine based on age/sex
• Adequate Liver Function defined as:
• Direct bilirubin < 1.5 x upper limit of normal (ULN), and
• Alkaline phosphatase ≤ 2.5 x ULN, and
• Serum glutamic pyruvic transaminase (SGPT) alanine aminotransferase (ALT) ≤
• 5 x ULN. If liver abnormality is due to radiographically identifiable leukemia infiltrate, the participant will remain eligible.
• Cardiac performance: Minimum cardiac function defined as:
• No history of congestive heart failure in need of medical treatment
• No pre-treatment diminished left ventricular function on echocardiography (shortening fraction [SF] < 25% or ejection fraction [EF] < 40%)
• No signs of congestive heart failure at presentation of relapse.
• Participant, parent or guardian must sign and date informed consent and pediatric assent (when required), prior to the initiation of screening or study specific procedures, according to local law and legislation. Exclusion Criteria
• Participants who in the opinion of the investigator may not be able to comply with the study requirements of the study, are not eligible.
• Participants with Down syndrome.
• Participants with Acute promyelocytic leukemia (APL) or Juvenile myelomonocytic leukemia (JMML).
• Participants with isolated CNS3 disease or symptomatic CNS3 disease.
• Participants with malabsorption syndrome or any other condition that precludes enteral administration of venetoclax.
• Participants who are currently receiving another investigational drug (GO is not considered investigational in this study).
• Participants with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known congenital bone marrow failure syndrome.
• Participants with known prior allergy to any of the medications used in protocol therapy.
• Participants with documented active, uncontrolled infection at the time of study entry.
• No known human immunodeficiency virus (HIV) infection.
• Post menarchal female participants with positive pregnancy test.
• Concomitant Medications
• Participants who have received strong and moderate CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort within 7 days of the start of study treatment.
• Participants who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit within 3 days of the start of study treatment.
• Participants who have hypersensitivity to the active substance or to any of the excipients listed in summary of product characteristics (SPC).
• Pregnancy or Breast-Feeding:
• Participants who are pregnant or breast-feeding.
• Participants of reproductive potential may not participate unless they have agreed to use a highly effective contraceptive method per clinical trials facilitation group (CTFG) guidelines for the duration of study therapy and for 6 months after the completion of all study therapy.
• Male participants must use a condom during intercourse and agree not to father a child or donate sperm during therapy and for the duration of study therapy and for 4 months after the completion of all study therapy. Additional criteria to receive a gemtuzumab ozogamicin infusion: Gemtuzumab ozogamicin should not be given:
• to participants with history of veno-occlusive disease (VOD)/Sinusoidal obstruction syndrome (SOS) grade 4
• to participants with history of VOD/SOS grade 3
• to participants with CD33 negative leukemic blasts (determined at local lab) Note that these participants are eligible for the study but will not be treated with gemtuzumab ozogamicin.
• Participants must have enrolled on APAL2020SC, NCT Number: NCT04726241 prior to enrollment on ITCC-101/APAL2020D. (This is only applicable for participants in USA/Canada/Australia/New Zealand sites/LLS territory).
• Participants must be ≥ 29 days of age and ≤ 21 years of age at enrollment.
• Participants must have one of the following:
• Children, adolescents, and young adults with acute myeloid leukemia without FLT3/internal tandem duplication (ITD) mutation in:
• Second relapse, who are sufficiently fit to undergo another round of intensive chemotherapy
• First relapse who per investigator discretion cannot tolerate additional anthracycline containing chemotherapy.
• Participants must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2 (≥ 50% Lansky or Karnofsky score)
• Participants must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to start of protocol treatment:
• Cytotoxic chemotherapy: Must not have received cytotoxic chemotherapy within 14 days prior to start of protocol treatment, except for corticosteroids, low dose cytarabine or hydroxyurea that can be given up to 24 hours prior to start of protocol treatment.
• Intrathecal cytotoxic therapy: No wash-out time is required for participants having received any combination of intrathecal cytarabine, methotrexate, and/or hydrocortisone.
• Antibodies: ≥ 21 days must have elapsed from infusion of last dose of an antibody-drug conjugate before start of protocol treatment. For unmodified antibodies or T cell engaging antibodies, 2 half-lives must have elapsed before start of protocol treatment. Any toxicity related to prior antibody therapy must be recovered to Grade ≤ 1.
• Interleukins, Interferons and Cytokines (other than Hematopoietic Growth Factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than Hematopoietic Growth Factors) before start of protocol treatment.
• Hematopoietic growth factors: ≥ 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or ≥7 days for short-acting growth factor before start of protocol treatment.
• Radiation therapy (RT) (before start of protocol treatment):
• ≥ 14 days have elapsed for local palliative RT (small port);
• ≥ 84 days must have elapsed if prior craniospinal RT or if ≥ 50% radiation of pelvis;
• ≥ 42 days must have elapsed if other substantial bone marrow (BM) radiation.
• Stem Cell Infusions (before start of protocol treatment):
• ≥ 84 days since allogeneic (non-autologous) bone marrow or stem cell transplant (with or without total body irradiation [TBI]) or boost infusion (any stem cell product; not including donor lymphocyte infusion [DLI])
• No evidence of active graft versus host disease (GVHD).
• Participants who are receiving cyclosporine, tacrolimus or other agents to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial. Participants must be off medications to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant for at least 14 days prior to enrollment.
• Cellular Therapy: ≥ 42 days after the completion of donor lymphocyte infusion (DLI) or any type of cellular therapy (e.g., modified T cells, natural killer [NK] cells, dendritic cells, etc.) before start of protocol treatment.
• Participants with prior exposure to venetoclax are eligible in this trial
• Adequate organ function:
• Adequate Renal Function defined as:
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 60ml/min/1.73 m^2, or
• Normal serum creatinine based on age/sex
• Adequate Liver Function defined as:
• Direct bilirubin < 1.5 x upper limit of normal (ULN), and
• Alkaline phosphatase ≤ 2.5 x ULN, and
• Serum glutamic pyruvic transaminase (SGPT) alanine aminotransferase (ALT) ≤
• 5 x ULN. If liver abnormality is due to radiographically identifiable leukemia infiltrate, the participant will remain eligible.
• Cardiac performance: Minimum cardiac function defined as:
• No history of congestive heart failure in need of medical treatment
• No pre-treatment diminished left ventricular function on echocardiography (shortening fraction [SF] < 25% or ejection fraction [EF] < 40%)
• No signs of congestive heart failure at presentation of relapse.
• Participant, parent or guardian must sign and date informed consent and pediatric assent (when required), prior to the initiation of screening or study specific procedures, according to local law and legislation. Exclusion Criteria
• Participants who in the opinion of the investigator may not be able to comply with the study requirements of the study, are not eligible.
• Participants with Down syndrome.
• Participants with Acute promyelocytic leukemia (APL) or Juvenile myelomonocytic leukemia (JMML).
• Participants with isolated CNS3 disease or symptomatic CNS3 disease.
• Participants with malabsorption syndrome or any other condition that precludes enteral administration of venetoclax.
• Participants who are currently receiving another investigational drug (GO is not considered investigational in this study).
• Participants with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known congenital bone marrow failure syndrome.
• Participants with known prior allergy to any of the medications used in protocol therapy.
• Participants with documented active, uncontrolled infection at the time of study entry.
• No known human immunodeficiency virus (HIV) infection.
• Post menarchal female participants with positive pregnancy test.
• Concomitant Medications
• Participants who have received strong and moderate CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort within 7 days of the start of study treatment.
• Participants who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit within 3 days of the start of study treatment.
• Participants who have hypersensitivity to the active substance or to any of the excipients listed in summary of product characteristics (SPC).
• Pregnancy or Breast-Feeding:
• Participants who are pregnant or breast-feeding.
• Participants of reproductive potential may not participate unless they have agreed to use a highly effective contraceptive method per clinical trials facilitation group (CTFG) guidelines for the duration of study therapy and for 6 months after the completion of all study therapy.
• Male participants must use a condom during intercourse and agree not to father a child or donate sperm during therapy and for the duration of study therapy and for 4 months after the completion of all study therapy. Additional criteria to receive a gemtuzumab ozogamicin infusion: Gemtuzumab ozogamicin should not be given:
• to participants with history of veno-occlusive disease (VOD)/Sinusoidal obstruction syndrome (SOS) grade 4
• to participants with history of VOD/SOS grade 3
• to participants with CD33 negative leukemic blasts (determined at local lab) Note that these participants are eligible for the study but will not be treated with gemtuzumab ozogamicin.
Drug: Fludarabine, Drug: Cytarabine, Drug: Gemtuzumab Ozogamicin, Drug: Azacitidine, Drug: Venetoclax
Acute Myeloid Leukemia, Leukemia, Other, Leukemia, Not Otherwise Specified
Venetoclax, Gemtuzumab Ozogamicin, Fludarabine, Cytarabine, Relapsed refractory, Azacitidine
Children’s Health
Pediatric Radiation Oncology With Movie Induced Sedation Effect (PROMISE)
PROMISE (Pediatric Radiation Oncology with Movie Induced Sedation Effect) is an interactive incentive-based movie system that integrates with a video surveillance gating module (VisionRT) as an alternative sedation solution for pediatric patients undergoing radiation treatment (RT). This single-arm, open label, single-center phase II clinical trial is to implement PROMISE for all children ages 3-11 who are planned to undergo RT at the institution. The primary goal is to decrease the total number of pediatric patients who require general anesthesia through the use of PROMISE, with secondary goals being to assess the impact that PROMISE has on patient/family anxiety and quality of life, treatment time and clinical efficiency, and overall cost. The investigators hypothesize that PROMISE will lead to a reduction in the percentage of patients ages 3-7 who require general anesthesia use from 70% (historical control) to 30%.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kiran Kumar
181795
All
3 Years to 11 Years old
Phase 2
NCT05148078
STU-2021-1005
Inclusion Criteria:
• Planned to undergo radiation treatment
• Age 3-11 years
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at screening
• Parents or guardians with the ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
• Subjects with documented medical behavior conditions or other conditions necessitating anesthesia use
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects whose parents opt to not include them (the subject) in the clinical trial.
Other: PROMISE (Pediatric Radiation Oncology with Movie Induced Sedation Effect)
Multiple Myeloma, Pediatric Cancer, Brain and Nervous System, Eye and Orbit, Bones and Joints, Kidney, Lip, Oral Cavity and Pharynx, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Rectum, Thyroid, Leukemia, Other, Leukemia, Not Otherwise Specified, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Non-Hodgkins Lymphoma, Other Hematopoietic, Soft Tissue
radiotherapy
UT Southwestern; Children’s Health
Caloric Restriction and Activity to Reduce Chemoresistance in B-ALL (IDEAL2)
This study is for older children, adolescents, and young adults with B-cell Acute Lymphoblastic Leukemia (B-ALL). Higher amounts of body fat is associated with resistance to chemotherapy in patients with B-ALL. Chemotherapy during the first month causes large gains in body fat in most people, even those who start chemotherapy at a healthy weight. This study is being done to find out if caloric restriction achieved by a personalized nutritional menu and exercise plan during routine chemotherapy can make the patient's ALL more sensitive to chemotherapy and also reduce the amount of body fat gained during treatment. The goals of this study are to help make chemotherapy more effective in treating the patient's leukemia as demonstrated by fewer patients with leukemia minimal residual disease (MRD) while also trying to reduce the amount of body fat that chemotherapy causes the patient to gain in the first month.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
67555
All
10 Years to 25 Years old
Phase 2
NCT05082519
STU-2022-0479
Inclusion Criteria:
• Patients must be ≥ 10.0 and <26.0 years of age.
• Patients must have a diagnosis of de novo B-ALL
• Patients must have a M3 marrow (>25% blasts by morphology) or at least 1,000/µL circulating leukemia cells in PB confirmed by Flow Cytometry (or other convincing evidence of a B-ALL diagnosis not meeting above criteria following central review by the Study Hematopathologist and Study Chair or Vice-Chair).
• The treatment regimen must be the first treatment attempt for B-ALL-
• Must be a multi-agent induction regimen inclusive of vincristine, glucocorticoid, pegaspargase/calaspargase, and daunorubicin or doxorubicin and with a planned duration <35 days.
• Organ function must meet that required for initiation of chemotherapy
• Patients at diagnosis must meet Karnofsky > 50% for patients > 16 years of age and Lansky > 50% for patients ≤ 16 years of age (or be expected to recover prior to Day 8) .
• If the patient is a female of childbearing potential, a negative urine or serum pregnancy test is required within two weeks prior to enrollment.
Exclusion Criteria:
• Patient will be excluded if they are underweight at time of enrollment (BMI% <5th percentile for age for patients age 10-19 years, BMI <18.5 in patients 20-29 years).
• Patients with Down syndrome or a DNA fragility syndrome (such as Fanconi anemia, Bloom syndrome) will be excluded.
• Patient receiving a SJCRH-style "Total Therapy" regimen will be excluded.
• Patients receiving anti-CD20 monoclonal antibody therapy during induction therapy.
• Patients will be excluded if they received treatment for a previous malignancy.
• Patient will be excluded if they are pregnant.
• Patient will be excluded if they have a pre-diagnosis requirement for enteral or parenteral supplementation .
• Patient will be excluded due to inability to perform the intervention (e.g., specific nutritional needs, severe developmental delay, paraplegia)
• Patients will be excluded if they have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results
Behavioral: IDEAL2 Intervention
Obesity, B-cell Acute Lymphoblastic Leukemia, Lymphoid Leukemia
obesity, leukemia, B-cell leukemia, Pediatric obesity, Pediatric ALL
Children’s Health
Study of Selinexor and Venetoclax in Combination With Chemotherapy in Pediatric and Young Adult Patients With Refractory or Relapsed Acute Myeloid Leukemia
The purpose of this study is to test the safety and determine the best dose of venetoclax and selinexor when given with chemotherapy drugs in treating pediatric and young adult patients with acute myeloid leukemia (AML) or acute leukemia of ambiguous lineage (ALAL) that has come back (relapsed) or did not respond to treatment (refractory). Primary Objective - To determine the safety and tolerability of selinexor and venetoclax in combination with chemotherapy in pediatric patients with relapsed or refractory AML or ALAL. Secondary Objectives - Describe the rates of complete remission (CR) and complete remission with incomplete count recovery (CRi) for patients treated with selinexor and venetoclax in combination with chemotherapy at the recommended phase 2 dose (RP2D). - Describe the overall survival of patients treated at the RP2D. Exploratory Objectives - Explore associations between leukemia cell genomics, BCL2 family member protein quantification, BH3 profiling, and response to therapy as assessed by minimal residual disease (MRD) and variant clearance using cell-free deoxyribonucleic acid (DNA) (cfDNA). - Describe the quality of life of pediatric patients undergoing treatment with selinexor and venetoclax in combination with chemotherapy and explore associations of clinical factors with patient-reported quality of life outcomes. - Describe the clinical and genetic features associated with exceptional response to the combination of venetoclax and selinexor without the addition of chemotherapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kathleen Ludwig
114894
All
2 Years to 30 Years old
Phase 1
NCT04898894
STU-2021-0697
Inclusion Criteria:
• Participants must have a diagnosis of AML or ALAL and meet the criteria below:
• Refractory leukemia, defined as persistent leukemia after at least two courses of induction chemotherapy, OR
• Early relapsed leukemia, defined as the re-appearance of leukemia after the achievement of remission and within one year of diagnosis, OR
• Relapsed leukemia that is refractory to at least one course of salvage therapy (i.e., therapy given after the relapse has occurred), OR
• Relapsed leukemia following HCT, OR
• Second or greater relapse
• Patients with late first relapses, defined as the re-appearance of leukemia after the achievement of remission and greater than one year of diagnosis, may be enrolled in the dose expansion portion of the study after safety data from the dose escalation portion is available. Patients must have ≥ 5% blasts in the bone marrow as assessed by morphology or flow cytometry. However, if flow cytometry cannot be performed or if an adequate bone marrow sample cannot be obtained (e.g., in a patient with acute megakaryoblastic leukemia with marrow fibrosis), patients may be enrolled if there is unequivocal evidence of leukemia with ≥ 5% blasts in the blood. In addition, patients in all categories must not be eligible to undergo curative therapy, such as immediate HCT, because of disease burden, time to identify a stem cell donor, or other reasons.
• Adequate organ function defined as the following:
• Direct bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
• Normal creatinine for age or a calculated creatinine clearance ≥ 30 mL/min/1.73m^2
• Left ventricular ejection fraction ≥ 40% or shortening fraction ≥ 25%
• Patients must be ≥ 2 years of age and ≤ 30 years old. The upper age limit may be defined by each institution, but may not exceed 30 years. Patients treated at St. Jude Children's Research Hospital must be ≤ 24 years old.
• Performance status: Lansky ≥ 50 for patients who are ≤ 16 years old and Karnofsky ≥ 50% for patients who are > 16 years old.
• At least 14 days must have elapsed since the completion of myelosuppressive therapy or hypomethylating agents and the first doses of venetoclax and selinexor.
• At least 24 hours must have elapsed since the completion of low-dose or non- myelosuppressive therapy, such as hydroxyurea or low-dose cytarabine (up to 100 mg/m^2/day), or leukapheresis, and the first doses of venetoclax and selinexor.
• For patients who have received prior HCT, there can be no evidence of GVHD and greater than 60 days must have elapsed since the HCT.
• At least 14 days must have elapsed since the completion of any calcineurin inhibitors (e.g. tacrolimus, cyclosporine).
• Patients may not receive strong or moderate CYP3A inducers, such as rifampin, within 3 days of the first dose of venetoclax or during the administration of venetoclax. During the dose-escalation portion of the trial, we discourage the use of strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, voriconazole, posaconazole) within 3 days of the first dose of venetoclax or during the administration of venetoclax. However, if an azole is required for the treatment or prevention of fungal infection during any phase of the trial, venetoclax dosing will be reduced to 60 mg/m^2 (100 mg max) in patients who require treatment with voriconazole and reduced to 40 mg/m^2 (70 mg max) in patients who require posaconazole.
Exclusion Criteria:
• Must not be pregnant or breastfeeding. Male or female of reproductive potential must agree to use effective contraception for the duration of study participation.
• Patients with Down syndrome, acute promyelocytic leukemia, juvenile myelomonocytic leukemia, or bone marrow failure syndromes are not eligible.
• Uncontrolled infection. Patients with infections that are controlled on concurrent anti-microbial agents are eligible.
• Impairment of GI function or GI disease that, in the opinion of the treating physician, may significantly alter the absorption of venetoclax or selinexor.
• History of cerebellar toxicity or cerebellar neurological findings on exam.
• Previous toxicity or hypersensitivity directly attributed to venetoclax.
Drug: Venetoclax, Drug: Selinexor, Drug: Cytarabine, Drug: Fludarabine, Biological: Filgrastim, Drug: Methotrexate, Drug: methotrexate/hydrocortisone/cytarabine
Refractory Acute Myeloid Leukemia, Myeloid and Monocytic Leukemia, Acute Leukemia of Ambiguous Lineage in Relapse, Acute Myeloid Leukemia, in Relapse, Refractory Acute Leukemia of Ambiguous Lineage
Acute Myeloid Leukemia, in Relapse, Refractory Acute Myeloid Leukemia, Acute Leukemia of Ambiguous Lineage in Relapse, Refractory Acute Leukemia of Ambiguous Lineage, Pediatric, Young Adult
Children’s Health
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
114894
All
up to 22 Years old
Phase 1/Phase 2
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:
• Patient has known or suspected relapsed/refractory (including primary refractory) AML
• This includes isolated myeloid sarcoma
• Patient has known or suspected relapsed/refractory (including primary refractory) myeloid leukemia of Down syndrome
• Patient has known or suspected relapsed ALL 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)
• Patient has known or suspected de novo or relapsed/refractory (including primary refractory) treatment-related AML (t-AML) or treatment-related myelodysplastic syndrome (t-MDS)
• Patient has known or suspected de novo or relapsed/refractory (including primary refractory) myelodysplastic syndrome (MDS)
• Patient has known or suspected de novo or relapsed/refractory (including primary refractory) juvenile myelomonocytic leukemia (JMML)
• 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, Myelodysplastic Syndrome, Juvenile Myelomonocytic Leukemia, Acute Myeloid Leukemia, Myeloid Leukemia Associated With Down Syndrome, Mixed Phenotype Acute Leukemia, Acute Myeloid Leukemia Post Cytotoxic Therapy, Myelodysplastic Syndrome Post Cytotoxic Therapy
Children’s Health
The OPAL Study: AVM0703 for Treatment of Lymphoid Malignancies (OPAL)
This is an open-label, Phase 1/2 study designed to characterize the safety, tolerability, Pharmacokinetics(PK), and preliminary antitumor activity of AVM0703 administered as a single intravenous (IV) infusion to patients with lymphoid malignancies.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
67555
All
12 Years to 95 Years old
Phase 1/Phase 2
NCT04329728
STU-2021-0058
Inclusion Criteria:
• 1. Age ≥12 years and weight ≥40 kg;
• Histologically confirmed diagnosis per 2016 World Health Organization (WHO) classification of lymphoid neoplasms160 and per the 2016 WHO classification of acute leukemia161 of the following indications:
• DLBCL, including arising from follicular lymphoma;
• High-grade B-cell lymphoma;
• MCL;
• Primary mediastinal large B-cell lymphoma;
• Primary DLBCL of the CNS;
• Burkitt or Burkitt-like lymphoma/leukemia;
• CLL/SLL; or
• B-lymphoblastic leukemia/lymphoma, T-lymphoblastic leukemia/lymphoma, acute leukemia/lymphoma, acute leukemias of ambiguous lineage, or NK cell lymphoblastic leukemia/lymphoma;
• Patients must have relapsed or refractory (R/R) disease with prior therapies defined below:
• DLBCL and high-grade B-cell lymphoma: e) R/R after autologous hematopoietic cell transplant (HCT); or f) R/R after chimeric antigen receptor T-cell (CAR T) therapy; or g) Patients not eligible for autologous HCT or CAR T therapy; or h) R/R after ≥2 lines of therapy including anti-CD20 antibody and failed, intolerant or ineligible for polatuzamab vedotin, or for whom no standard therapy is available.
• MCL: c) R/R after autologous HCT; or d) Patients not eligible for autologous HCT must have failed acalabrutinib or be R/R after ≥2 lines of therapy including at least 1 of the following: a Bruton's tyrosine kinase (BTK) inhibitor, bortezomib, or lenalidomide; or for whom no standard therapy is available;
• Primary mediastinal large B-cell lymphoma: R/R after ≥1 line of therapy and are not eligible for or have recurred after autologous HCT or CAR T cell therapy, or for whom no standard therapy is available;
• Primary DLBCL of the CNS: R/R after ≥1 line of therapy including methotrexate (unless intolerant to methotrexate) and are not eligible for or have recurred after autologous HCT or CAR T cell therapy, or for whom no standard therapy is available;
• Burkitt or Burkitt-like lymphoma/leukemia: R/R after ≥1 line of therapy including methotrexate (unless intolerant to methotrexate) and are not eligible for or have recurred after autologous HCT or CAR T cell therapy, or for whom no standard therapy is available;
• CLL/SLL: patients who have active disease requiring treatment and who are deemed at high-risk for disease progression by the investigator or have high risk features per the iwCLL criteria, such as primary resistance to first-line chemo(immune)therapy, or progression of disease <3 years after fludarabine-based chemo(immune)therapy, or leukemia cells with del(17p)/TP53 mutation, must be: d) R/R after autologous or allogeneic HCT; or e) Patients not eligible for HCT; or f) R/R after ≥2 lines of therapy including at least 1 of the following: a BTK inhibitor, venetoclax, idelalisib, or duvelisib, or for whom no standard therapy is available;
• Acute lymphoblastic leukemia (ALL): c) R/R after allogeneic HCT and for whom no standard therapy is available; or d) Patients not eligible for allogeneic HCT must be R/R according to the following disease specific specifications:
• B-cell lymphoblastic leukemia/lymphoma: ≥2 lines of therapy including approved CAR T cell therapies, inotuzumab ozogamicin, or blinatumomab, or for whom no standard therapy is available;
• T-cell lymphoblastic leukemia/lymphoma: ≥2 lines of therapy including nelarabine, or for whom no standard therapy is available;
• NK cell leukemia/lymphoma: ≥1 line of therapy or for whom no standard therapy is available;
• All other diagnoses: R/R after autologous or allogeneic HCT; or R/R after at least one line of therapy, or for whom no standard therapy is available.
• Lansky (12 to 15 years of age) (Appendix G) or Karnofsky (≥16 years of age) (Appendix H) performance status ≥50;
• Screening laboratory values that meet all of the following criteria:
• Absolute neutrophil count ≥0.05 × 109/L;
• Platelet count ≥25 × 109/L;
• Hemoglobin ≥6.5 g/dL;
• • Aspartate aminotransferase or alanine aminotransferase ≥2.5 × ULN, unless due to the disease;
• Total bilirubin <1.5 × ULN (if secondary to Gilbert's syndrome, <3 × ULN is permitted), unless due to the disease; and
• Glomerular filtration rate ≥30 mL/min ; except for patients on metformin at baseline GFR must be ≥45 mL/min; GFR can be calculated by the Cockcroft-Gault formula Appendix C);
• Minimum level of pulmonary reserve defined as
• The ability to understand and willingness to sign a written informed consent form (ICF) and the ability to adhere to the study schedule and prohibitions. Patients under the age of 18 years (or other age as defined by regional law or regulation) must be willing and able to provide written assent and have a parent(s) or guardian(s) willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to performance of any study-related procedure.
Exclusion Criteria:
• Patients who meet any of the following criteria will be excluded from participation in the study for Phase 2:
• History of another malignancy, except for the following:
• Adequately treated local basal cell or squamous cell carcinoma of the skin;
• Adequately treated carcinoma in situ without evidence of disease;
• Adequately treated papillary, noninvasive bladder cancer; or
• Other cancer that has been in complete remission for ≥2 years. Patients with low-grade prostate cancer, on active surveillance, and not expected to clinically progress over 2 years are allowed;
• Significant cardiovascular disease (e.g., myocardial infarction, arterial thromboembolism, cerebrovascular thromboembolism) within 3 months prior to the start of AVM0703 administration, angina requiring therapy, symptomatic peripheral vascular disease, New York Heart Association Class III or IV congestive heart failure, left ventricular ejection fraction <30%, left ventricular fractional shortening <20%, or uncontrolled ≥Grade 3 hypertension (diastolic blood pressure >100 mmHg or systolic blood pressure >150 mmHg) despite antihypertensive therapy for patients ≥18 years of age, or uncontrolled stage 2 hypertension (diastolic blood pressure >90 mmHg or systolic blood pressure >140 mmHg) despite antihypertensive therapy for patients ≥12 years of age;
• Significant screening electrocardiogram (ECG) abnormalities, including unstable cardiac arrhythmia requiring medication, atrial fibrillation/flutter, second degree atrioventricular (AV) block type 2, third-degree AV block, ≥Grade 2 bradycardia, or heart rate corrected QT interval using Fridericia's formula >480 msec;
• Known gastric or duodenal ulcer;
• Uncontrolled type 1 or type 2 diabetes;
• Known hypersensitivity or allergy to the study drug or any of its excipients;
• Untreated ongoing bacterial, fungal, or viral infection (including upper respiratory tract infections) at the start of AVM0703 administration, including the following:
• Positive hepatitis B surface antigen and/or hepatitis B core antibody test plus a positive hepatitis B polymerase chain reaction (PCR) assay. Patients with a negative PCR assay are permitted with appropriate antiviral prophylaxis;
• Positive hepatitis C virus antibody (HCV Ab) test. Patients with a positive HCV Ab test are eligible if they are negative for hepatitis C virus by PCR;
• Positive human immunodeficiency virus (HIV) antibody test with detectable HIV load by PCR, or the patient is not able to tolerate antiretroviral therapy; or
• Positive tuberculosis test during screening; test must be positive and not indeterminate due to anergy; if the result is indeterminate due to anergy the patient must not have a history of recent exposure to tuberculosis. Patients in Phase 2 repeat dosing cohorts should not travel to any destination where they might be exposed to tuberculosis during their entire treatment period with AVM0703.
• Received live vaccination within 8 weeks of screening;
• Pregnant or breastfeeding;
• Concurrent participation in another therapeutic clinical study (except AVM0703-001); or
• Uncontrolled bipolar disorder or schizophrenia. Patients with a diagnosis, past or current, of bipolar disorder or schizophrenia or having a history of severe depression or substance abuse must be prophylactically treated with circadian physiologic hydrocortisone per section 5.5.3.3 CNS prophylaxis, without exception.
Drug: AVM0703
Lymphoma, Lymphoid Leukemia, Lymphoid Malignancies
Diffuse large B-cell lymphoma (DLBCL), B-cell lymphoma, Mantle cell lymphoma (MCL), Primary mediastinal large B-cell Lymphoma, Primary DLBCL of the central nervous system (CNS), Burkitt or Burkitt-like lymphoma/leukemia, Chronic lymphocytic leukemia (CLL), Small lymphocytic leukemia (SLL), B-cell leukemia/lymphoma, T-cell leukemia/lymphoma, Acute leukemias of ambiguous lineage, Natural Killer (NK) cell lymphoblastic leukemia/lymphoma, Advanced or Aggressive lymphoma/lymphoproliferative disease, Follicular Lymphoma
Children’s Health
Enasidenib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia Patients With an IDH2 Mutation
This trial studies the side effects of enasidenib and to see how well it works in treating patients with acute myeloid leukemia that has come back after treatment (relapsed) or has been difficult to treat with chemotherapy (refractory). Patients must also have a specific genetic change, also called a mutation, in a protein called IDH2. Enasidenib may stop the growth of cancer cells by blocking the mutated IDH2 protein, which is needed for cell growth.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kathleen Ludwig
114894
All
24 Months to 21 Years old
Phase 2
NCT04203316
STU-2020-0395
Inclusion Criteria:
• Patients must be >= 24 months and < 21 years of age at the time of study enrollment
• Patient must have AML with an IDH2 mutation identified from a peripheral blood or bone marrow sample at the time of diagnosis and/or relapsed/refractory disease
• Patient must have bone marrow assessment (aspiration or biopsy) with > 5% leukemic blasts by morphology and/or flow cytometry in at least one of the following clinical scenarios:
• Second or greater relapse after chemotherapy or hematopoietic stem cell transplant (HSCT)
• Refractory after >= 2 attempts at induction therapy
• Relapsed patients
• Must not have received prior re-induction therapy for this relapse
• Each block of chemotherapy (i.e., cytarabine, daunorubicin and etoposide [ADE], cytarabine and mitoxantrone [MA]) is a separate re-induction attempt
• Donor lymphocyte infusion (DLI) is considered a re-induction attempt
• Refractory patients
• Each attempt at induction therapy may include up to two chemotherapy courses
• Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
• Evaluation of cerebrospinal fluid (CSF) is only required if there is a clinical suspicion of central nervous system (CNS) involvement by leukemia during eligibility screening. Should a patient be found to have CNS2 or CNS3 status by CSF prior to eligibility screening, patient may receive intrathecal chemotherapy > 72 hours prior to starting study drug. CNS1 status must be established before starting study drug
• 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 numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive. The duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
• >= 14 days must have elapsed after the completion of other cytotoxic therapy with the exception of hydroxyurea. Additionally, patients must have fully recovered from all acute toxic effects of prior therapy. NOTE: Cytoreduction with hydroxyurea must be discontinued >= 24 hours prior to the start of protocol therapy
• Intrathecal chemotherapy must be completed >= 72 hours prior to the start of the first cycle of treatment
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent. The duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair and the study research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
• Stem cell Infusions (with or without total body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion:
• >= 60 days after infusion for bone marrow or stem cell transplant and
• >= 4 weeks after infusion for any stem cell infusion including DLI or boost infusion
• There must be no evidence of graft versus host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular Therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
• XRT/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-metaiodobenzylguanidine [MIBG]): >= 42 days after systemically administered radiopharmaceutical therapy
• Study-specific limitations on prior therapy: small molecule investigational agents: >= 14 days or > 5 half-lives must have elapsed from the last dose of the agent, whichever is greater
• Platelet count >= 20,000/mm^3 (may receive platelet transfusions)
• Hemoglobin >= 8.0 g/dL at baseline (may receive red blood cell [RBC] transfusions)
• Creatinine clearance or radioisotope glomerular filtration rate [GFR] >= 70 ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• Age: Maximum serum creatinine (mg/dL)
• 2 to < 6 years: 0.8 (male and female)
• 6 to < 10 years: 1 (male and female)
• 10 to < 13 years: 1.2 (male and female)
• 13 to < 16 years: 1.5 (male); 1.4 (female)
• >= 16 years: 1.7 (male); 1.4 (female)
• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 225 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L
• Serum albumin >= 2 g/dL
• Left ventricular ejection fraction of >= 50% by echocardiogram
• Regulatory Requirements
• All patients and/or their parents or legal authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
• AML associated with Down syndrome or t(15;17) is not eligible for study
• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study therapy and for 2 months after the last dose of enasidenib. Abstinence is an acceptable method of birth control. It is not known if enasidenib is present in breast milk. Breastfeeding is not recommended during therapy or for at least 30 days after the last dose of enasidenib
• Concomitant Medications:
• Corticosteroids: Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid. The use of corticosteroids to manage the side effect of IDH inhibitor-associated differentiation syndrome (IDH-DS), is permitted on study
• Investigational drugs: Patients who are currently receiving another investigational drug are not eligible
• Anti-cancer agents: Patients who are currently receiving other anti-cancer agents are not eligible (except leukemia patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy; the use of hydroxyurea to manage the side effect of IDH-DS, is permitted on study)
• 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
• Patients must be able to swallow intact tablets whole or use the alternate enasidenib formulation.
• Patients with known hypersensitivity to any of the components of enasidenib are not eligible.
• Patients with prior exposure to enasidenib or another IDH2 inhibitor are not eligible.
• Patients taking the following drugs will be excluded from study entry unless these drugs are discontinued or patients are transferred to a medically acceptable alternative > 5 half-lives before the first dose of enasidenib.
• Drugs with a narrow therapeutic range that are sensitive substrates of the following cytochrome P450 (CYP) enzymes: CYP2C8 (e.g. paclitaxel), 2C9 (e.g. phenytoin and warfarin), 2C19 (e.g. s-mephenytoin), 2D6 (e.g. thioridazine), and 1A2 (e.g. theophylline and tizanidine).
• Breast cancer resistant protein (BCRP) transporter-sensitive substrate rosuvastatin
• Patients with the following leukemia complications are not eligible for this trial:
• No intrathecal chemotherapy is permitted on study. Prior to study enrollment, cerebrospinal fluid (CSF) evaluation is only required if there is a clinical suspicion for CNS leukemia. Clinical signs of CNS leukemia (such as facial nerve palsy, brain/eye involvement or hypothalamic syndrome) are not eligible for this trial
• Immediately life-threatening, severe complications of leukemia including uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation
• Patients who have received a prior solid organ transplantation are not eligible
• Infection: Patients who have an uncontrolled infection or patients with known human immunodeficiency virus (HIV) or active hepatitis B or C are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspiration, Procedure: Bone Marrow Biopsy, Drug: Enasidenib, Drug: Enasidenib Mesylate
Refractory Acute Myeloid Leukemia, Recurrent Acute Myeloid Leukemia, Leukemia, Other
Children’s Health
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
67555
All
1 Year to 25 Years old
Phase 3
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, Central Nervous System Leukemia, Testicular Leukemia, Mixed Phenotype Acute Leukemia, B Lymphoblastic Lymphoma
Children’s Health
A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia
This phase III trial studies how well blinatumomab works in combination with chemotherapy in treating patients with newly diagnosed, standard risk B-lymphoblastic leukemia or B-lymphoblastic lymphoma with or without Down syndrome. Monoclonal antibodies, such as blinatumomab, may induce changes in the body's immune system and may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs, such as vincristine, dexamethasone, prednisone, prednisolone, pegaspargase, methotrexate, cytarabine, mercaptopurine, doxorubicin, cyclophosphamide, and thioguanine, 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. Leucovorin decreases the toxic effects of methotrexate. Giving monoclonal antibody therapy with chemotherapy may kill more cancer cells. Giving blinatumomab and combination chemotherapy may work better than combination chemotherapy alone in treating patients with B-ALL. This trial also assigns patients into different chemotherapy treatment regimens based on risk (the chance of cancer returning after treatment). Treating patients with chemotherapy based on risk may help doctors decide which patients can best benefit from which chemotherapy treatment regimens.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
67555
All
365 Days to 31 Years old
Phase 3
NCT03914625
STU-2019-1128
Inclusion Criteria:
• All B-ALL patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part A) prior to treatment and enrollment on AALL1731. APEC 14B1 is not a requirement for B-LLy patients. B-LLy patients may directly enroll on AALL1731.
• Age at diagnosis:
• Patients must be >= 365 days and < 10 years of age (B-ALL patients without DS).
• Patients must be >= 365 days and =< 31 years of age (B-ALL patients with DS).
• Patients must be >= 365 days and =< 31 years of age (B-LLy patients with or without DS).
• B-ALL patients without DS must have an initial white blood cell count < 50,000/uL (performed within 7 days prior to enrollment).
• B-ALL patients with DS are eligible regardless of the presenting white blood cell count (WBC) (performed within 7 days prior to enrollment).
• Patient has newly diagnosed B-cell ALL, with or without Down syndrome: > 25% blasts on a bone marrow (BM) aspirate;
• OR if a BM aspirate is not obtained or is not diagnostic of B-ALL, the diagnosis can be established by a pathologic diagnosis of B-ALL on a BM biopsy;
• OR a complete blood count (CBC) documenting the presence of at least 1,000/uL circulating leukemic cells;
• OR patient has newly diagnosed B-cell LLy Murphy stages I or II, with or without Down syndrome.
• 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 (diagnostic biopsy for B-LLy must be performed within 14 days prior to enrollment).
• 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:
• Patient must not have secondary ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy. Note: patients with Down syndrome with a prior history of transient myeloproliferative disease (TMD) are not considered to have had a prior malignancy. They would therefore be eligible whether or not the TMD was treated with cytarabine.
• With the exception of steroid pretreatment or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for either the current diagnosis of B ALL or B LLy or for any cancer diagnosed prior to initiation of protocol therapy on AALL1731.
• For patients receiving steroid pretreatment, the following additional exclusion criteria apply:
• Non-DS B-ALL patients must not have received steroids for more than 24 hours in the 2 weeks prior to diagnosis without a CBC obtained within 3 days prior to initiation of the steroids.
• DS and non-DS B-LLy patients must not have received > 48 hours of oral or IV steroids within 4 weeks of diagnosis.
• Patients who have received > 72 hours of hydroxyurea within 1 week (7 days) prior to the start of systemic protocol therapy.
• B-ALL patients who do not have sufficient diagnostic bone marrow submitted for APEC14B1 diagnostic testing and who do not have a peripheral blood sample submitted containing > 1,000/uL circulating leukemia cells.
• Patient must not have acute undifferentiated leukemia (AUL).
• Non-DS B-ALL patients with central nervous system [CNS]3 leukemia (CNS status must be known prior to enrollment).
• Note: DS patients with CNS3 disease are eligible but will be assigned to the DS-High B-ALL arm. CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment.
• Non-DS B-ALL patients with testicular leukemia. (Note: DS patients with testicular disease are eligible but will be assigned to the DS-High B-ALL arm).
• For LLy patients, 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.
• CNS positive disease or testicular involvement.
• M2 (5% - 25% blasts) or M3 (> 25% blasts) marrow.
• 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 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.
Drug: Asparaginase Erwinia chrysanthemi, Biological: Blinatumomab, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Dexamethasone, Drug: Doxorubicin Hydrochloride, Drug: Leucovorin Calcium, Drug: Mercaptopurine, Drug: Mercaptopurine Oral Suspension, Drug: Methotrexate, Drug: Pegaspargase, Drug: Prednisolone, Drug: Prednisone, Radiation: Radiation Therapy, Radiation: Radiation Therapy, Drug: Thioguanine, Drug: Vincristine Sulfate
B Acute Lymphoblastic Leukemia, Down Syndrome, B Lymphoblastic Lymphoma
Children’s Health
Study of Efficacy and Safety of Tisagenlecleucel in HR B-ALL EOC MRD Positive Patients (CASSIOPEIA)
This is a single arm, open-label, multi-center, phase II study to determine the efficacy and safety of tisagenlecleucel in de novo HR pediatric and young adult B-ALL patients who received first-line treatment and are EOC MRD positive. The study will have the following sequential phases: screening, pre-treatment, treatment & follow-up, and survival. After tisagenlecleucel infusion, patient will have assessments performed more frequently in the first month and then at Day 29, then every 3 months for the first year, every 6 months for the second year, then yearly until the end of the study. Efficacy and safety will be assessed at study visits and as clinically indicated throughout the study. The study is expected to end in approximately 8 years after first patient first treatment (FPFT). A post-study long term follow-up safety will continue under a separate protocol per health authority guidelines.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Samuel John
125571
All
1 Year to 25 Years old
Phase 2
NCT03876769
STU-2019-0770
Inclusion Criteria:
• CD19 expressing B-cell Acute Lymphoblastic Leukemia
• De novo NCI HR B-ALL who received first-line treatment and are MRD ≥ 0.01% at EOC. EOC bone marrow MRD will be collected prior to screening and will be assessed by multi-parameter flow cytometry using central laboratory analysis.
• Age 1 to 25 years at the time of screening
• Lansky (age < 16 years) or Karnofsky (age ≥ 16 years) performance status ≥ 60%
• Adequate organ function during the screening period: A. Renal function based on age/gender B. ALT ≤ 5 times ULN for age C. AST ≤ 5 times ULN for age D. Total bilirubin < 2 mg/dL (for Gilbert's Syndrome subjects total bilirubin < 4 mg/dL) E. Adequate pulmonary function defined as:
• no or mild dyspnea (≤ Grade 1)
• oxygen saturation of > 90% on room air F. Adequate cardiac function defined as LVSF ≥ 28% confirmed by echocardiogram or LVEF ≥ 45% confirmed by echocardiogram or MUGA within 6 weeks of screening
• Prior induction and consolidation chemotherapy allowed: 1st line subjects: ≤ 3 blocks of standard chemotherapy for first-line B-ALL, defined as 4-drug induction, Berlin-Frankfurt-Münster (BFM) consolidation or Phase 1b, and interim maintenance with high-dose methotrexate.
Exclusion Criteria:
• M3 marrow at the completion of 1st line induction therapy
• M2 or M3 marrow or persistent extramedullary disease at the completion of first-line consolidation therapy or evidence of disease progression in the peripheral blood or new extramedullary disease prior to enrollment. Patients with previous CNS disease are eligible if there is no active CNS involvement of leukemia at the time of screening.
• Philadelphia chromosome positive ALL
• Hypodiploid: less than 44 chromosomes and/or DNA index < 0.81, or other clear evidence of a hypodiploid clone
• Prior tyrosine kinase inhibitor therapy
• Subjects with concomitant genetic syndromes associated with bone marrow failure states: such as subjects with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome. Subjects with Down syndrome will not be excluded.
• Subjects with Burkitt's lymphoma/leukemia (i.e. subjects with mature B-ALL, leukemia with B-cell [sIg positive and kappa or lambda restricted positivity] ALL, with FAB L3 morphology and /or a MYC translocation)
• Has had treatment with any prior anti-CD19 therapy 9. Treatment with any prior gene or engineered T cell therapy Other protocol-defined inclusion/exclusion may apply.
Biological: CTL019
B-cell Acute Lymphoblastic Leukemia, Lymphoid Leukemia
CTL019, Kymriah, B-Cell Acute Lymphoblastic Leukemia, ALL, tisagenlecleucel, HR B-ALL EOC MRD, Minimal Residual Disease (MRD), Positive at the End of Consolidation (EOC)
Children’s Health
Stopping Tyrosine Kinase Inhibitors in Affecting Treatment-Free Remission in Patients With Chronic Phase Chronic Myeloid Leukemia
This phase II trial studies how stopping tyrosine kinase inhibitors will affect treatment-free remission in patients with chronic myeloid leukemia in chronic phase. When the level of disease is very low, it's called molecular remission. TKIs are a type of medication that help keep this level low. However, after being in molecular remission for a specific amount of time, it may not be necessary to take tyrosine kinase inhibitors. It is not yet known whether stopping tyrosine kinase inhibitors will help patients with chronic myeloid leukemia in chronic phase continue or re-achieve molecular remission.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
67555
All
up to 25 Years old
Phase 2
NCT03817398
STU-2019-1261
Inclusion Criteria:
• Patient must have been diagnosed with CML-CP at < 18 years of age.
• Patient must have histologic verification of CML-CP at original diagnosis
• Patient must be in molecular remission (MR) with a BCR-ABL1 level of =< 0.01% BCR-ABL1 as measured using the International Scale (IS) by RQ-PCR for >= 2 consecutive years at the time of enrollment
• Please note: The lab evaluating disease status and molecular response for this study must be College of American Pathology (CAP) and/or Clinical Laboratory Improvement Amendments (CLIA) certified (United States [US] only), sites in other countries must be certified by their accredited authorities. All labs must use the International Scale guidelines with a sensitivity of detection assay =< 0.01% BCR-ABL1 and be able to report results in =< 2 weeks
• Patient must have received any TKI for a minimum of 3 consecutive years at time of enrollment
• Patient agrees to discontinue TKI therapy
• REGULATORY REQUIREMENTS
• 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
• ELIGIBILITY FOR PATIENT-REPORTED OUTCOMES (PROs):
• Age >= 8 years at the time of enrollment
• Ability to understand English or Spanish
• Cognitive ability to complete instruments according to the primary team
• ELIGIBILITY FOR AAML18P1 NEUROCOGNITIVE STUDY:
• Patient must be 5 years or older at the time of enrollment
• English-, French- or Spanish-speaking
• No known history of neurodevelopmental disorder prior to diagnosis of CML (e.g., Down syndrome, Fragile X, William syndrome, mental retardation)
• No significant visual or motor impairment that would prevent computer use or recognition of visual test stimuli
Exclusion Criteria:
• Known T3151 mutation
• Additional clonal chromosomal abnormalities in Philadelphia chromosome (Ph) positive (+) cells at any time prior to enrollment that include "major route" abnormalities (second Ph, trisomy 8, isochromosome 17q, trisomy 19), complex karyotype or abnormalities of 3q26.2
• History of accelerated phase or blast crisis CML
• Female patients who are pregnant
• Lactating females are not eligible unless they have agreed not to breastfeed their infants
• Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
Procedure: Biospecimen Collection, Other: Drug Withdrawn, Other: Quality-of-Life Assessment, Other: Questionnaire Administration, Drug: Tyrosine Kinase Inhibitor
Chronic Phase Chronic Myeloid Leukemia, BCR-ABL1 Positive
UT Southwestern; Children’s Health
Safety and Efficacy of Quizartinib in Children and Young Adults With Acute Myeloid Leukemia (AML), a Cancer of the Blood
Quizartinib is an experimental drug. It is not approved for regular use. It can only be used in medical research. Children or young adults with a certain kind of blood cancer (FLT3-ITD AML) might be able to join this study if it has come back after remission or is not responding to treatment.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kathleen Ludwig
114894
All
1 Month to 21 Years old
Phase 1/Phase 2
NCT03793478
STU-2019-1283
Inclusion Criteria:
Participants must meet all of the following criteria to be eligible for enrollment into the
study:
• Has diagnosis of AML according to the World Health Organization (WHO) 2008 classification with ≥5% blasts in bone marrow, with or without extramedullary disease
• In first relapse or refractory to first-line high-dose chemotherapy with no more than 1 attempt (1 to 2 cycles of induction chemotherapy) at remission induction - prior HSCT is permitted
• Has presence of the FLT3-ITD activating mutation in bone marrow or peripheral blood as defined in the protocol
• Is between 1 month and 21 years of age at the time the Informed Consent/Assent form is signed
• Has protocol-defined adequate performance status score
• Has fully recovered from the acute clinically significant toxicity effects of all prior chemotherapy, immunotherapy, or radiotherapy, per protocol guidelines
• Has protocol-defined adequate renal, hepatic and cardiac functions
• If of reproductive potential, is permanently sterile or agrees to use highly effective birth control upon enrollment, during the period of therapy, and for 6 months following the last dose of quizartinib, etoposide, fludarabine, methotrexate, or cytarabine, whichever is later
• If female of child-bearing potential, tests negative for pregnancy and agrees not to breast feed
• Male participants must be surgically sterile or willing to use highly effective birth control during the treatment period, and for 6 months following the last dose of quizartinib, etoposide, fludarabine, methotrexate, or cytarabine, whichever is later.
• Participant/legal representative is capable of understanding the investigational nature of the study, potential risks, and benefits, and the patient (and/or legal representative) signs a written assent/informed consent
Exclusion Criteria:
Participants who meet any of the following criteria will be disqualified from entering the
study:
• Has been diagnosed with isolated central nervous system relapse, acute promyelocytic leukemia (APL), juvenile myelomonocytic leukemia, French-American-British classification M3 or WHO classification of APL with translocation, or with myeloid proliferations related to Down syndrome
• Has uncontrolled or pre-defined significant cardiovascular disease as detailed in the protocol
• Has systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. The patient must be off vasopressors and have negative blood cultures for at least 48 hours prior to the start of systematic protocol therapy.
• Has known active clinically relevant liver disease (e.g., active hepatitis B or active hepatitis C)
• Has known history of human immunodeficiency virus (HIV)
• Has history of hypersensitivity to any of the study medications or their excipients
• Is receiving or is anticipated to receive concomitant chemotherapy, radiation, or immunotherapy other than as specified in the protocol
• Has any significant concurrent disease, illness, psychiatric disorder or social issue that would compromise subject safety or compliance, interfere with consent/assent, study participation, follow up, or interpretation of study results
• Is currently participating in another investigative interventional procedure (observational or long-term interventional follow-up is allowed)
• Is otherwise considered inappropriate for the study by the Investigator
Drug: Quizartinib, Drug: Fludarabine, Drug: Cytarabine, Drug: Intrathecal (IT) triple chemotherapy prophylaxis, Drug: Etoposide
Acute Myeloid Leukemia, Myeloid and Monocytic Leukemia
Acute myeloid leukemia recurrent, Relapsed or refractory, FMS-like tyrosine kinase 3 positive, Cancer of the blood, AML, FLT3-ITD mutation
Children’s Health
Imatinib Mesylate and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia
This randomized phase III trial studies how well imatinib mesylate works in combination with two different chemotherapy regimens in treating patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (ALL). Imatinib mesylate has been shown to improve outcomes in children and adolescents with Philadelphia chromosome positive (Ph+) ALL when given with strong chemotherapy, but the combination has many side effects. This trial is testing whether a different chemotherapy regimen may work as well as the stronger one but have fewer side effects when given with imatinib. The trial is also testing how well the combination of chemotherapy and imatinib works in another group of patients with a type of ALL that is similar to Ph+ ALL. This type of ALL is called "ABL-class fusion positive ALL", and because it is similar to Ph+ ALL, is thought it will respond well to the combination of agents used to treat Ph+ ALL.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
67555
All
1 Year to 21 Years old
Phase 3
NCT03007147
STU 082017-074
Inclusion Criteria:
• For patients enrolled on APEC14B1 prior to enrollment on AALL1631, the required diagnostic bone marrow sample has been fulfilled
• For patients who have not previously enrolled on APEC14B1 prior to enrollment on AALL1631, a baseline diagnostic sample (or peripheral blood sample with blasts if marrow sample unavailable) must be available to develop an MRD probe
• In addition, laboratory reports detailing evidence of BCR-ABL1 fusion or ABL-class fusion must be submitted for rapid central review within 72 hours of study enrollment
• >= 1 year (365 days) and =< 21 years at ALL diagnosis
• Ph+ (BCR-ABL1 fusion): newly diagnosed de novo ALL (B-ALL or T-ALL) or mixed phenotypic acute leukemia (MPAL meeting 2016 World Health Organization [WHO] definition) with definitive evidence of BCR-ABL1 fusion by karyotype, fluorescence in situ hybridization (FISH) and/or molecular methodologies
• ABL-class fusion: newly diagnosed B-ALL with definitive evidence of ABL-class fusions. ABL-class fusions are defined as those involving the following genes: ABL1, ABL2, CSF1R, PDGFRB, PDGFRA. Methods of detection include fluorescence in-situ hybridization (FISH, e.g. using break-apart or colocalization signals probes), multiplex or singleplex reverse-transcription polymerase chain reaction (RT-PCR), whole transcriptome or panel-based ribonucleic acid (RNA)-sequencing (e.g. TruSight RNA Pan-Cancer Panel; Illumina, San Diego, CA, USA or similar)
• Ph+ patients must have previously started Induction therapy, which includes vincristine, a corticosteroid, pegaspargase, with or without anthracycline, and/or other standard cytotoxic chemotherapy
• Ph+ patients have not received more than 14 days of multiagent Induction therapy beginning with the first dose of vinCRIStine
• Ph+ patients may have started imatinib prior to study entry but have not received more than 14 days of imatinib
• ABL-class fusion patients must have previously completed the 4 or 5 weeks of multiagent Induction chemotherapy (Induction IA phase)
• ABL-class fusion patients may have started imatinib during Induction IA, at the same time of or after the first vinCRIStine dose
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2
• Direct bilirubin =< 2.0 mg/dL
• Shortening fraction of >= 27% by echocardiogram
• Ejection fraction of >= 50% by radionuclide angiogram or echocardiogram
• Corrected QT interval, QTc < 480 msec
• Note: Repeat echocardiogram and electrocardiogram are not required if they were performed at or after initial ALL diagnosis, before study enrollment
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or serum creatinine within normal limits based on age/gender, as follows:
• 1 to < 2 years: maximum serum creatinine 0.6 mg/dL (both male and female)
• 2 to < 6 years: maximum serum creatinine 0.8 mg/dL (both male and female)
• 6 to < 10 years: maximum serum creatinine 1 mg/dL (both male and female)
• 10 to < 13 years: maximum serum creatinine 1.2 mg/dL (both male and female)
• 13 to < 16 years: maximum serum creatinine 1.5 mg/dL (male), 1.4 mg/dL (female)
• >= 16 years: maximum serum creatinine 1.7 mg/dL (male), 1.4 mg/dL (female)
Exclusion Criteria:
• Known history of chronic myelogenous leukemia (CML)
• ALL developing after a previous cancer treated with cytotoxic chemotherapy
• Active, uncontrolled infection, or active systemic illness that requires ongoing vasopressor support or mechanical ventilation
• Down syndrome
• Pregnancy and breast feeding
• 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 treatment according to protocol
• Patients with congenital long QT syndrome, history of ventricular arrhythmias or heart block
• Prior treatment with dasatinib, or any TKI other than imatinib
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation, Drug: Calaspargase Pegol, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Daunorubicin Hydrochloride, Drug: Dexamethasone, Drug: Dexrazoxane Hydrochloride, Drug: Doxorubicin, Drug: Etoposide, Biological: Filgrastim, Drug: Ifosfamide, Drug: Imatinib Mesylate, Other: Laboratory Biomarker Analysis, Drug: Leucovorin Calcium, Drug: Mercaptopurine, Drug: Mercaptopurine, Drug: Methotrexate, Drug: Methylprednisolone, Drug: Pegaspargase, Drug: Prednisolone, Other: Questionnaire Administration, Drug: Therapeutic Hydrocortisone, Drug: Thioguanine, Drug: Vincristine Sulfate
Acute Lymphoblastic Leukemia, B Acute Lymphoblastic Leukemia, Mixed Phenotype Acute Leukemia, T Acute Lymphoblastic Leukemia, Leukemia, Other
Children’s Health
Inotuzumab Ozogamicin in Treating Younger Patients With B-Lymphoblastic Lymphoma or Relapsed or Refractory CD22 Positive B Acute Lymphoblastic Leukemia
This phase II trial studies how well inotuzumab ozogamicin works in treating younger patients with B-lymphoblastic lymphoma or CD22 positive B acute lymphoblastic leukemia that has come back (relapsed) or does not respond to treatment (refractory). Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a toxic agent called ozogamicin. Inotuzumab attaches to CD22 positive cancer cells in a targeted way and delivers ozogamicin to kill them.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
67555
All
1 Year to 21 Years old
Phase 2
NCT02981628
STU 062017-028
Inclusion Criteria:
• Patients must be >= 1 year and < 22 years of age at the time of enrollment
• Patients must have B-ALL, or previously diagnosed B lymphoblastic lymphoma (B-LL), with >= 5% (M2 or M3) bone marrow blasts with or without extramedullary disease
• NOTE: Relapsed patients previously diagnosed with B-lymphoblastic lymphoma (B-LL) are eligible if they have an M2 or M3 marrow at the time of enrollment on this study
• Patients with ALL or B-LL who have M2 morphology must have local confirmatory testing showing >= 5% blasts by flow cytometry, fluorescence in situ hybridization (FISH) testing or other molecular method
• Leukemic blasts must demonstrate surface expression of CD22 at the time of relapse by local/institutional flow cytometry of a bone marrow aspirate sample; (assessment of CD22 using a bright fluorophore such as phycoerythrin [PE] is strongly recommended)
• In the case of an inadequate aspirate sample (dry tap) or if bone marrow aspirate is unable to be performed due to patient clinical status, flow cytometry of peripheral blood specimen may be substituted if the patient has at least 1,000/uL circulating blasts; alternatively, CD22 expression may be documented by immunohistochemistry of a bone marrow biopsy specimen
• Patients with one of the following:
• Second or greater relapse;
• Primary refractory disease with at least 2 prior induction attempts;
• First relapse refractory to at least one prior re-induction attempt
• Any relapse after HSCT (Cohort 1 ONLY) Patients with Down syndrome are eligible ONLY for Cohort 1 with:
• Any of above disease status, OR
• First relapse with no prior re-induction attempt NOTE: Patients with Down syndrome or prior HSCT are NOT eligible for Cohort 2 combination therapy
• Patients with Philadelphia chromosome (Ph)+ ALL must have had two prior therapy attempts including two different tyrosine kinase inhibitors (TKIs)
• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy, defined as resolution of all such toxicities to =< grade 2 or lower per the inclusion/exclusion criteria prior to entering this study. Apply to Cohort 2:
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment.
• A waiting period prior to enrollment is not required for patients receiving standard cytotoxic maintenance chemotherapy (i.e., corticosteroid, vincristine, 6MP, and/or methotrexate).
• A waiting period is not required for patients receiving a single dose of intrathecal methotrexate, hydrocortisone, and/or cytarabine within 7 days prior to enrollment
• >= 14 days must have elapsed after the completion of other cytotoxic therapy, with the exception of hydroxyurea, for patients not receiving standard maintenance therapy. For patients who previously received calaspargase pegol, >= 21 days must have elapsed after the last dose. Additionally, patients must have fully recovered from all acute toxic effects of prior therapy.
• Note: Cytoreduction with hydroxyurea must be discontinued >= 24 hours prior to the start of protocol therapy.
• Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment.
• Anti-cancer agents that are antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1. There is an exception for blinatumomab infusions, for which patients must have been off for at least 3 days and all drug related toxicity must have resolved to grade 2 or lower as outlined in the inclusion/exclusion criteria.
• Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid. A waiting period prior to enrollment is not required for patients receiving corticosteroid for leukemia therapy/cytoreduction.
• Radiotherapy: >= 2 weeks must have elapsed since local palliative radiation therapy (XRT) (small port); >= 3 months must have elapsed if prior cranial or craniospinal XRT was received, if >= 50% of the pelvis was irradiated, or if total body irradiation (TBI) was received; >= 6 weeks must have elapsed if other substantial bone marrow irradiation was given.
• Stem cell transplant or rescue without TBI: For Cohort 1, at least 90 days must have elapsed since stem cell transplant and at least 30 days from donor lymphocyte infusion. Patient must have had no more than one previous HSCT and currently have no evidence of active graft vs. host disease (GVHD). For Cohort 2, no prior HSCT is allowed.
• Chimeric antigen receptor (CAR) T cell therapy: At least 30 days must have elapsed from the last CAR-T cell infusion
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or
• A serum creatinine based on age/gender as follows:
• 1 to < 2 years: maximum serum creatinine 0.6 mg/dL (both male and female)
• 2 to < 6 years: maximum serum creatinine 0.8 mg/dL (both male and female)
• 6 to < 10 years: maximum serum creatinine 1 mg/dL (both male and female)
• 10 to < 13 years: maximum serum creatinine 1.2 mg/dL (both male and female)
• 13 to < 16 years: maximum serum creatinine 1.5 mg/dL (male), 1.4 mg/dL (female)
• >= 16 years: maximum serum creatinine 1.7 mg/dL (male), 1.4 mg/dL (female)
• Direct bilirubin =< 1.5 x upper limit of normal (ULN) for age, and
• Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 5 x ULN for age; for the purpose of this study, the ULN for ALT will be 45 U/L
Exclusion Criteria:
• Patients with any prior history of SOS irrespective of severity
• Patients with isolated central nervous system (CNS), testicular, or any other extramedullary site of relapse
• Patients who have been previously treated with inotuzumab ozogamicin
• Patients who have previously received HSCT (Cohort 2 only)
• Patients with Down syndrome (Cohort 2 only)
• History of allergic reaction attributed to compounds of similar or biologic composition to inotuzumab ozogamicin or other agents in the study
• Note: Patients with history of allergy to pegaspargase/calaspargase pegol are eligible for enrollment on Cohort 2 if Erwinia formulation of asparaginase can be obtained
• Patients with active optic nerve and/or retinal involvement are not eligible; patients who are presenting with visual disturbances should have an ophthalmologic exam and, if indicated, a magnetic resonance imaging (MRI) to assess optic nerve or retinal involvement
• Patients who are currently receiving another investigational drug
• Patients who are currently receiving or plan to receive other anti-cancer agents (except hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy, and intrathecal chemotherapy)
• Anti-GVHD or agents to prevent organ rejection post-transplant; patients who are receiving cyclosporine, tacrolimus, or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial; at least 3 half-lives must have elapsed after the last dose of GVHD or anti-rejection medications
• Patients who are currently receiving or plan to receive corticosteroids except as described below
• Systemic corticosteroids may be administered for cytoreduction up to 24 hours prior to the start of protocol therapy, (Cohort 1 only) for all patients, corticosteroids may be administered as a premedication for inotuzumab ozogamicin and as treatment for allergic reactions or for physiologic replacement/stress dosing of hydrocortisone for documented adrenal insufficiency; corticosteroids are not allowed for other indications
• Patients with known human immunodeficiency virus (HIV), hepatitis B or C infections; testing to prove negative status is not required for enrollment unless it is deemed necessary for usual medical care of the patient
• Patients who have an active uncontrolled infection defined as:
• Positive bacterial blood culture within 48 hours of study enrollment;
• Fever above 38.2 degree Celsius (C) within 48 hours of study enrollment with clinical signs of infection; fever that is determined to be due to tumor burden is allowed if patients have documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability
• A positive fungal culture within 30 days of study enrollment or active therapy for presumed invasive fungal infection
• Patients may be receiving IV or oral antibiotics to complete a course of therapy for a prior documented infection as long as cultures have been negative for at least 48 hours and signs or symptoms of active infection have resolved; for patients with clostridium (C.) difficile diarrhea, at least 72 hours of antibacterial therapy must have elapsed and stools must have normalized to baseline
• Active viral or protozoal infection requiring IV treatment
• Patients known to have one of the following concomitant genetic syndromes: Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Schwachman (Schwachman-Diamond-Blackfan) syndrome or any other known bone marrow failure syndrome
• There have been no human studies of inotuzumab ozogamicin in pregnant women and no reports of exposure in utero; based on nonclinical safety studies, inotuzumab ozogamicin has the potential to impair human male and female fertility and to adversely affect human embryo fetal development; women of childbearing potential should be advised to avoid becoming pregnant while receiving inotuzumab ozogamicin; there is no information regarding the presence of inotuzumab ozogamicin in human milk, the effects on the breast-fed infant, or the effects on milk production; because of the potential for adverse reactions in breast-fed infants, women should not breast-feed during treatment with inotuzumab ozogamicin and for at least 2 months after the final dose
• Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained within 7 days prior to enrollment
• Female patients who are sexually active and of reproductive potential are not eligible unless they agree to use an effective contraceptive method for the duration of their study participation and for 8 months after the last dose of inotuzumab ozogamicin
• Men with female partners of childbearing potential should use effective contraception during treatment with inotuzumab ozogamicin and for at least 5 months after the last dose of inotuzumab ozogamicin
• Lactating females are not eligible unless they agree not to breastfeed their infants
Drug: Asparaginase Erwinia chrysanthemi, Procedure: Biospecimen Collection, Procedure: Bone Marrow Aspiration and Biopsy, Drug: Calaspargase Pegol, Drug: Cyclophosphamide, Drug: Cytarabine, Procedure: Diagnostic Imaging, Biological: Inotuzumab Ozogamicin, Drug: Leucovorin Calcium, Procedure: Lumbar Puncture, Drug: Methotrexate, Drug: Pegaspargase, Drug: Vincristine
Recurrent B Acute Lymphoblastic Leukemia, Recurrent B Lymphoblastic Lymphoma, Refractory B Acute Lymphoblastic Leukemia, Refractory B Lymphoblastic Lymphoma
Children’s Health
CAR-T Long Term Follow Up (LTFU) Study (PAVO)
Per Health Authorities guidelines for gene therapy medicinal products that utilize integrating vectors (e.g. lentiviral vectors), long term safety and efficacy follow up of treated patients is required. The purpose of this study is to monitor all patients exposed to CAR-T therapied for 15 years following their last CAR-T (e.g. CTL019) infusion to assess the risk of delayed adverse events (AEs), monitor for replication competent lentivirus (RCL) and assess long-term efficacy, including vector persistence.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Samuel John
125571
All
Not specified
Phase 3
NCT02445222
STU 032015-068
Inclusion Criteria:
• All patients who have received a CAR-T therapy and completed or discontinued early from a Novartis sponsored treatment protocol that utilized CAR-T cells or from any CAR-T trial sponsored by the University of Pennsylvania with which Novartis has a contractual agreement to co-develop the CAR technology.
• Patients who have provided informed consent for the long term follow up study prior to their study participation .
Exclusion Criteria:
• There are no specific exclusion criteria for this study.
Genetic: Previously treated CAR-T patients
Long Term Safety of Patients Receiving CAR-T in an Eligible Clinical Trial or Managed Access Program, Leukemia, Other
Children’s Health
Vincristine Sulfate Liposome Injection (Marqibo®) in Combination With UK ALL R3 Induction Chemotherapy for Children, Adolescents, and Young Adults With Relapsed ALL
This is a pilot study utilizing Marqibo® (vincristine sulfate liposome injection) combined with dexamethasone, mitoxantrone and asparaginase (UK ALL R3) for relapsed acute lymphoblastic leukemia (ALL).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
67555
All
1 Year to 21 Years old
Phase 1
NCT02879643
STU 082016-009
Inclusion Criteria
Age
-Patients must be ≥ 1 and ≤ 21 years of age at the time of enrollment.
Diagnosis
• Cohort A: Patients must have a diagnosis of acute lymphoblastic leukemia (ALL) or mixed phenotypic acute leukemia with ≥ 5% blasts in the bone marrow (M2 or M3), with or without extramedullary disease) or a diagnosis of lymphoblastic lymphoma.
• Cohorts B & C: Patients must have a diagnosis of acute lymphoblastic leukemia (ALL), lymphoblastic lymphoma, or mixed phenotypic acute leukemia with any level of detectable disease (minimal residual disease level acceptable) with or without extramedullary disease Performance Level -Karnofsky > 50% for patients > 16 years of age and Lansky > 50% for patients ≤ 16 years of age. Prior Therapy
• Patients must have recovered from the acute toxic effects (≤ Grade 2 or baseline) of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study, unless otherwise specified. Subjects with disease related cytopenias will be eligible.
• Patients must have relapsed or refractory disease after attaining at least a first remission. They may be in first to third relapse..
• Patients with Philadelphia chromosome t(9;22) positive disease must have received at least two prior tyrosine kinase inhibitors.
• Patients who have experienced their relapse after a Hematopoietic stem cell transplantation (HSCT) are eligible, provided they have no evidence of graft-versus-host disease (GVHD) and are at least 100 days post-transplant at the time of enrollment.
• Prior anthracycline lifetime cumulative exposure: Patients must have less than 320 mg/m2 (or 400 mg/m2 if prior cardioprotection) lifetime exposure of anthracycline chemotherapy.
• Cohort A: Patients must have less than 320 mg/m2 (or 400 mg/m2 if prior cardioprotection) lifetime exposure of anthracycline chemotherapy (See Appendix 2 for anthracycline calculation worksheet).
• Cohorts B & C: There is no limit on prior anthracycline exposure.
• Hematopoietic growth factors: It must have been at least seven days since the completion of therapy with granulocyte colony-stimulating factor (GCSF) or other growth factors at the time of enrollment. It must have been at least 14 days since the completion of therapy with pegfilgrastim (Neulasta®).
• Biologic anti-neoplastic agents: At least seven days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond seven days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair or vice chair.
• Monoclonal antibodies: At least three half-lives (or 30 days—whichever is longer) of the antibody must have elapsed after the last dose of monoclonal antibody. (e.g., Rituximab = 66 days, Epratuzumab = 69 days)
• Immunotherapy: At least 30 days after the completion of any type of immunotherapy, e.g. tumor vaccines, chimeric antigen receptor T-cells.
• Recent prior chemotherapy: At least 10 days after standard vincristine and the completion of any type of chemotherapy induction regimen. At least 3 weeks after radiation therapy. At least 30 days after the completion of any investigational neoplastic agent is also required. An investigational agent is defined as any drug that is not approved and licensed for sale by the FDA for institutions in the United States, by Health Canada for institutions in Canada and by The Therapeutic Goods Administration for institutions in Australia. Exceptions:
• There is no time restriction in regard to prior intrathecal chemotherapy provided there is complete recovery from any acute toxic effects of such; it is allowable to enroll a patient that has received IT Cytarabine (ARA-C), IT Methotrexate (MTX) or triple IT therapy within 14 days of enrollment as part of their evaluation to diagnose disease relapse. The IT therapy given within 14 days of initiation of protocol specified chemotherapy, may substitute for the day 1 IT in cohorts A and B
• Subjects with rapidly progressive disease may receive hydroxyurea until they begin study therapy;
• Patients who relapse while on maintenance-type ALL therapy or are receiving maintenance therapy for disease stabilization will not require a wash-out period before entry into this study. However, there must be at least 10 days after any dose of standard vincristine. Renal and Hepatic Function
• Renal function: Patient's serum creatinine must be ≤ 1.5 x institutional upper limit of normal (ULN) according to age. If the serum creatinine is greater than 1.5 times normal, the patient must have a calculated creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70milliliter/min/1.73m2. Alternatively, a 24-hour creatinine clearance may also be used.
• Hepatic function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be < 5 x institutional upper limit of norm ULN. Total bilirubin must be ≤ 1.5 x ULN (except in the case of subjects with documented Gilbert's disease ≤ 5 × ULN). Cardiac Function -Patients must have a shortening fraction ≥ 27% or an ejection fraction ≥ 55% by echocardiogram, cardiac MRI or multigated acquisition scan (MUGA). Reproductive Function
• Female patients must not be pregnant and those of childbearing potential must have a negative urine or serum pregnancy test confirmed within one week prior to enrollment.
• Female patients with infants must agree not to breastfeed their infants while on this study.
• Male and female patients of childbearing potential must agree to use an effective method of contraception during the study. Exclusion Criteria Patients will be excluded if they have isolated testicular disease. Patients will be excluded if they have previously received Marqibo®. Patients will be excluded if they have a known allergy to any of the drugs used in the study, with the exception that patients with an allergy to PEG-asparaginase who can receive Erwinia asparaginase are eligible. Patients unable to receive any formulation of asparaginase may only enroll on cohort C Patients will be excluded if they have active, uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics or other treatment. Patients who require azole antifungal agents will be excluded. Azoles must be discontinued at least one week prior to the start of Marqibo®. Patients will be excluded if there is a plan to administer non-protocol chemotherapy, radiation therapy, another investigational agent or immunotherapy during the study period. Patients with pre-existing, persistent grade 2 or greater sensory or motor neuropathy from any cause will be excluded. Patients will be excluded if they have, significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or adherence with the protocol treatment or procedures or interfere with consent, study participation, follow up, or interpretation of study results.Patients with Down syndrome will not be eligible for enrollment on Cohort A Patients with a known history of human immunodeficiency virus (HIV) will will be excluded due to the increased risk of complications such as severe infection and unknown interaction of Marqibo® with antiretroviral drugs. Active hepatitis B or C infection as defined by seropositive for hepatitis B (hepatitis B surface antigen (HBsAg)) or hepatitis C and elevated liver transaminases (defined as above the ULN per the institution normal ranges).
• Cohort A: Patients must have a diagnosis of acute lymphoblastic leukemia (ALL) or mixed phenotypic acute leukemia with ≥ 5% blasts in the bone marrow (M2 or M3), with or without extramedullary disease) or a diagnosis of lymphoblastic lymphoma.
• Cohorts B & C: Patients must have a diagnosis of acute lymphoblastic leukemia (ALL), lymphoblastic lymphoma, or mixed phenotypic acute leukemia with any level of detectable disease (minimal residual disease level acceptable) with or without extramedullary disease Performance Level -Karnofsky > 50% for patients > 16 years of age and Lansky > 50% for patients ≤ 16 years of age. Prior Therapy
• Patients must have recovered from the acute toxic effects (≤ Grade 2 or baseline) of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study, unless otherwise specified. Subjects with disease related cytopenias will be eligible.
• Patients must have relapsed or refractory disease after attaining at least a first remission. They may be in first to third relapse..
• Patients with Philadelphia chromosome t(9;22) positive disease must have received at least two prior tyrosine kinase inhibitors.
• Patients who have experienced their relapse after a Hematopoietic stem cell transplantation (HSCT) are eligible, provided they have no evidence of graft-versus-host disease (GVHD) and are at least 100 days post-transplant at the time of enrollment.
• Prior anthracycline lifetime cumulative exposure: Patients must have less than 320 mg/m2 (or 400 mg/m2 if prior cardioprotection) lifetime exposure of anthracycline chemotherapy.
• Cohort A: Patients must have less than 320 mg/m2 (or 400 mg/m2 if prior cardioprotection) lifetime exposure of anthracycline chemotherapy (See Appendix 2 for anthracycline calculation worksheet).
• Cohorts B & C: There is no limit on prior anthracycline exposure.
• Hematopoietic growth factors: It must have been at least seven days since the completion of therapy with granulocyte colony-stimulating factor (GCSF) or other growth factors at the time of enrollment. It must have been at least 14 days since the completion of therapy with pegfilgrastim (Neulasta®).
• Biologic anti-neoplastic agents: At least seven days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond seven days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair or vice chair.
• Monoclonal antibodies: At least three half-lives (or 30 days—whichever is longer) of the antibody must have elapsed after the last dose of monoclonal antibody. (e.g., Rituximab = 66 days, Epratuzumab = 69 days)
• Immunotherapy: At least 30 days after the completion of any type of immunotherapy, e.g. tumor vaccines, chimeric antigen receptor T-cells.
• Recent prior chemotherapy: At least 10 days after standard vincristine and the completion of any type of chemotherapy induction regimen. At least 3 weeks after radiation therapy. At least 30 days after the completion of any investigational neoplastic agent is also required. An investigational agent is defined as any drug that is not approved and licensed for sale by the FDA for institutions in the United States, by Health Canada for institutions in Canada and by The Therapeutic Goods Administration for institutions in Australia. Exceptions:
• There is no time restriction in regard to prior intrathecal chemotherapy provided there is complete recovery from any acute toxic effects of such; it is allowable to enroll a patient that has received IT Cytarabine (ARA-C), IT Methotrexate (MTX) or triple IT therapy within 14 days of enrollment as part of their evaluation to diagnose disease relapse. The IT therapy given within 14 days of initiation of protocol specified chemotherapy, may substitute for the day 1 IT in cohorts A and B
• Subjects with rapidly progressive disease may receive hydroxyurea until they begin study therapy;
• Patients who relapse while on maintenance-type ALL therapy or are receiving maintenance therapy for disease stabilization will not require a wash-out period before entry into this study. However, there must be at least 10 days after any dose of standard vincristine. Renal and Hepatic Function
• Renal function: Patient's serum creatinine must be ≤ 1.5 x institutional upper limit of normal (ULN) according to age. If the serum creatinine is greater than 1.5 times normal, the patient must have a calculated creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70milliliter/min/1.73m2. Alternatively, a 24-hour creatinine clearance may also be used.
• Hepatic function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be < 5 x institutional upper limit of norm ULN. Total bilirubin must be ≤ 1.5 x ULN (except in the case of subjects with documented Gilbert's disease ≤ 5 × ULN). Cardiac Function -Patients must have a shortening fraction ≥ 27% or an ejection fraction ≥ 55% by echocardiogram, cardiac MRI or multigated acquisition scan (MUGA). Reproductive Function
• Female patients must not be pregnant and those of childbearing potential must have a negative urine or serum pregnancy test confirmed within one week prior to enrollment.
• Female patients with infants must agree not to breastfeed their infants while on this study.
• Male and female patients of childbearing potential must agree to use an effective method of contraception during the study. Exclusion Criteria Patients will be excluded if they have isolated testicular disease. Patients will be excluded if they have previously received Marqibo®. Patients will be excluded if they have a known allergy to any of the drugs used in the study, with the exception that patients with an allergy to PEG-asparaginase who can receive Erwinia asparaginase are eligible. Patients unable to receive any formulation of asparaginase may only enroll on cohort C Patients will be excluded if they have active, uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics or other treatment. Patients who require azole antifungal agents will be excluded. Azoles must be discontinued at least one week prior to the start of Marqibo®. Patients will be excluded if there is a plan to administer non-protocol chemotherapy, radiation therapy, another investigational agent or immunotherapy during the study period. Patients with pre-existing, persistent grade 2 or greater sensory or motor neuropathy from any cause will be excluded. Patients will be excluded if they have, significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or adherence with the protocol treatment or procedures or interfere with consent, study participation, follow up, or interpretation of study results.Patients with Down syndrome will not be eligible for enrollment on Cohort A Patients with a known history of human immunodeficiency virus (HIV) will will be excluded due to the increased risk of complications such as severe infection and unknown interaction of Marqibo® with antiretroviral drugs. Active hepatitis B or C infection as defined by seropositive for hepatitis B (hepatitis B surface antigen (HBsAg)) or hepatitis C and elevated liver transaminases (defined as above the ULN per the institution normal ranges).
Drug: Marqibo
ALL, Childhood, Lymphoblastic Leukemia, Acute, Childhood, Lymphoblastic Leukemia, Acute, Lymphoid Leukemia
Children’s Health
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, brittany.henderson@childrens.com
Victor Aquino
10208
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
Leukemia, Lymphoma, Aplastic Anemia, Myelodysplastic Syndrome (MDS), Unknown Sites
Unrelated Hematopoietic Stem Cell Transplantation, Cryopreserved Cord Blood Units, National Cord Blood Program
Children’s Health
PO Ixazomib in Combination With Chemotherapy for Childhood Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma
This is a phase 1/2 study of a drug called Ixazomib in combination with cytotoxic chemotherapy consisting of Vincristine, Dexamethasone, Asparaginase, and Doxorubicin (VXLD).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
67555
All
1 Year to 21 Years old
Phase 1
NCT03817320
STU-2019-0546
Inclusion Criteria:
• Age Patients must be ≤21 years of age at the time of enrollment.
• Phase 1 - Initial enrollment will be restricted to patients < 18 years of age until 9 such patients are enrolled
• Phase 2 - Initial enrollment will be restricted to patients < 18 years of age until 6 such patients are enrolled
• Diagnosis Patients must have a diagnosis of relapsed/refractory ALL or LLy with or without extramedullary disease (including CNS2 and CNS3). Patient with mixed phenotype ALL or mature B (Burkitt-like) leukemia are not eligible.
• Patients with ALL must have ≥ 5% blasts by morphology.
• Patients with LLy must have measurable disease documented by clinical, radiologic or histologic criteria
• Performance Level Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50% for patients ≤ 16 years of age.
• Prior Therapy A. Prior therapeutic attempts
• Phase 1 - Any patients with relapsed/refractory ALL or LLy
• Phase 2
• B-cell ALL/LLy: all patients must have failed two or more therapeutic attempts.
• T-cell ALL/LLy: all patients must have failed one or more therapeutic attempts. B. Recent prior chemotherapy Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
• Cytoreduction with hydroxyurea Hydroxyurea can be initiated and continued for up to 24 hours prior to the start of protocol therapy.
• Patients who relapsed while they are receiving cytotoxic therapy At least 14 days must have elapsed since the completion of the last dose of chemotherapy,except Intrathecal chemotherapy, and/or maintenance therapy such as vincristine, mercaptopurine, methotrexate or glucocorticoids. There is no waiting period for those relapsing on maintenance therapy. C. Hematopoietic stem cell transplant: Patients who have experienced their relapse after a HSCT are eligible, provided they have no evidence of acute or chronic Graft-versus-Host Disease (GVHD), are not receiving GVHD prophylaxis or treatment, and are at least 90 days post-transplant at the time of enrollment. D. Hematopoietic growth factors: It must have been at least 7 days since the completion of therapy with G-CSF or other growth factors at the time of enrollment. It must have been at least 14 days since the completion of therapy with pegfilgrastim (Neulasta®). E. Biologic (anti-neoplastic agent): At least 7 days since the last dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair
• Monoclonal antibodies: At least 3 half-lives of the antibody must have elapsed after the last dose of monoclonal antibody. (i.e., blinatumomab = 6 hours,44 inotuzumab = 37 days, rituximab = 66 days)
• Immunotherapy: At least 30 days after the completion of any type of immunotherapy, e.g., tumor vaccines, CAR T cells. F. XRT: Craniospinal XRT is prohibited during protocol therapy. No washout period is necessary for radiation given to any extramedullary site other than CNS; ≥90 days must have elapsed if prior total body irradiation (TBI) or craniospinal XRT. G. Anthracyclines: Patients must have had a lifetime exposure of <400 mg/m2 of doxorubicin equivalents of anthracyclines. H. Proteasome inhibitors: Patients with a prior exposure to proteasome inhibitors (e.g., bortezomib, carfilzomib) are eligible as long as the patient demonstrated at least a partial response to a proteasome inhibitor with chemotherapy combination. -Renal and hepatic function Patients must have adequate renal and hepatic functions as indicated by the following laboratory values: A. Adequate renal function defined as: Patient must have a calculated creatinine clearance or radioisotope GFR 70ml/min/1.73m2 OR a normal serum creatinine based on age/gender B. Adequate Liver Function Defined as: Direct bilirubin ≤ 1.5 x upper limit of normal (ULN) for age or normal (except in the presence of Gilbert's syndrome), AND alanine transaminase (ALT) ≤ 5 x ULN for age. The hepatic requirements are waived for patients with known or suspected liver involvement by leukemia or lymphoma. This must be reviewed by and approved by the study chair or vice chair.
• Adequate Cardiac Function Defined as: Shortening fraction of more than or equal to 27% by echocardiogram, OR ejection fraction of equal to or more than 50% by radionuclide angiogram (MUGA).
• Reproductive Function A. Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed within 2 weeks prior to enrollment. B. Female patients with infants must agree not to breastfeed their infants while on this study. C. Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study and for a minimum of 6 months after study treatment.
• Informed Consent Patients and/or their parents or legal guardians must be capable of understanding the investigational nature, potential risks and benefits of the study. All patients and/or their parents or legal guardians must sign a written informed consent. Age appropriate assent will be obtained per institutional guidelines. To allow non-English speaking patients to participate in this study, bilingual health services will be provided in the appropriate language when feasible.
• All institutional, FDA, and OHRP requirements for human studies must be met.
Exclusion Criteria:
Patients will be excluded if they have isolated CNS or testicular disease.
Patients will be excluded if they have ≥grade 2 peripheral sensory or motor neuropathy
(defined by the Modified "Balis" Pediatric Scale of Pediatric Neuropathies) at the time of
enrollment (see section 4.7.1.1).
Patients will be excluded if they have a known allergy or intolerance to any of the drugs
used in the study - except for PEG-asparaginase for which erwinia asparaginase may be
substituted
Patients will be excluded if they have a systemic fungal, bacterial, viral or other
infection that is exhibiting ongoing signs/symptoms related to the infection without
improvement despite appropriate antibiotics or other treatment. The patient needs to be off
pressors and have negative blood cultures for 48 hours.
Patients will be excluded if there is a plan to administer non-protocol chemotherapy,
radiation therapy, or immunotherapy during the study period.
Patients will be excluded if they have significant concurrent disease, illness, psychiatric
disorder or social issue that would compromise patient safety or compliance with the
protocol treatment or procedures, interfere with consent, study participation, follow up,
or interpretation of study results.
Patients with DNA fragility syndromes (such as Fanconi anemia, Bloom syndrome) are
excluded.
Patients will be excluded if they have had a lifetime exposure of ≥400 mg/m2 doxorubicin
equivolents of anthracyclines (anthracycline equivalence to doxorubicin conversion see
appendix iv) .
Concomitant medications Investigational drugs: Patients currently receiving another
investigational drug are not eligible.
Anti-GVHD agents post transplant: patients who are receiving cyclosporine, tacrolimus or
other agents to prevent graft-versus-host disease post hematopoetic stem cell transplant
are not eligible.
CYP3A4 agents: patients who are currently receiving drugs that are strong inducers of
CYP3A4 are not eligible. Strong inducers of CYP3A4 should be avoided from 14 days prior to
enrollment to the end of the study. See appendix ii for a list of agents which fall into
this category.
Patients with Ph+ALL and Ph-like ALL who are currently receiving TKI therapy
Infants or Patients with Down Syndrome will be excluded in phase 2 of the study
Drug: Ixazomib, Drug: Vincristine, Drug: Dexamethasone, Drug: Asparaginase, Drug: Doxorubicin
ALL, Childhood, Lymphoblastic Leukemia, Acute, Childhood, Lymphoblastic Lymphoma, Childhood, Lymphoid Leukemia
Children’s Health
Study of Ravulizumab in Pediatric Participants With HSCT-TMA
This study will evaluate the safety, efficacy, pharmacokinetics, and pharmacodynamics of ravulizumab administered by intravenous infusion to pediatric participants, from 1 month to < 18 years of age, with HSCT-TMA. The treatment period is 26 weeks, followed by a 26-week off-treatment follow-up period.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Victor Aquino
10208
All
1 Month to 17 Years old
Phase 3
NCT04557735
STU-2020-0967
Inclusion Criteria:
• 1 month of age up to < 18 years of age at the time of signing the informed consent.
• Received HSCT within the past 6 months.
• Diagnosis of TMA that persists despite initial management of any triggering condition.
• Body weight ≥ 5 kilograms.
• Female participants of childbearing potential and male participants with female partners of childbearing potential must use highly effective contraception starting at Screening and continuing until at least 8 months after the last dose of ravulizumab.
• Participants must be vaccinated against meningococcal infections if clinically feasible, according to institutional guidelines for immune reconstitution after HSCT. Participants must be re-vaccinated against Haemophilus influenzae type b and Streptococcus pneumoniae if clinically feasible, according to institutional guidelines for immune reconstitution after HSCT. All participants should be administered coverage with prophylactic antibiotics according to institutional post-transplant infection prophylaxis guidances, including coverage against Neisseria meningitidis for at least 2 weeks after meningococcal vaccination. Participants who cannot receive meningococcal vaccine should receive antibiotic prophylaxis coverage against Neisseria meningitidis the entire Treatment Period and for 8 months following the final dose of ravulizumab.
Exclusion Criteria:
• Known familial or acquired 'a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13' deficiency (activity < 5%).
• Known Shiga toxin-related hemolytic uremic syndrome.
• Positive direct Coombs test.
• Diagnosis or suspicion of disseminated intravascular coagulation.
• Known bone marrow/graft failure.
• Diagnosis of veno-occlusive disease.
• Human immunodeficiency virus (HIV) infection (evidenced by HIV-1 or HIV-2 antibody titer).
• Unresolved meningococcal disease.
• Presence or suspicion of sepsis (treated or untreated) within 7 days prior to Screening.
• Pregnancy or breastfeeding.
• Hypersensitivity to murine proteins or to 1 of the excipients of ravulizumab.
• Previously or currently treated with a complement inhibitor.
Drug: Ravulizumab, Other: Best Supportive Care
Brain and Nervous System, Kidney, Leukemia, Other, Hodgkins Lymphoma, Leukemia, Not Otherwise Specified, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Non-Hodgkins Lymphoma, Other Hematopoietic, Thrombotic Microangiopathy
Thrombotic Microangiopathy (TMA), Ultomiris, Ravulizumab, Hematopoietic Stem Cell Transplant
Children’s Health
Tagraxofusp in Pediatric Patients With Relapsed or Refractory CD123 Expressing Hematologic Malignancies
Tagraxofusp is a protein-drug conjugate consisting of a diphtheria toxin redirected to target CD123 has been approved for treatment in pediatric and adult patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN). This trial aims to examine the safety of this novel agent in pediatric patients with relapsed/refractory hematologic malignancies. The mechanism by which tagraxofusp kills cells is distinct from that of conventional chemotherapy. Tagraxofusp directly targets CD123 that is present on tumor cells, but is expressed at lower or levels or absent on normal hematopoietic stem cells. Tagraxofusp also utilizes a payload that is not cell cycle dependent, making it effective against both highly proliferative tumor cells and also quiescent tumor cells. The rationale for clinical development of tagraxofusp for pediatric patients with hematologic malignancies is based on the ubiquitous and high expression of CD123 on many of these diseases, as well as the highly potent preclinical activity and robust clinical responsiveness in adults observed to date. This trial includes two parts: a monotherapy phase and a combination chemotherapy phase. This design will provide further monotherapy safety data and confirm the FDA approved pediatric dose, as well as provide safety data when combined with chemotherapy. The goal of this study is to improve survival rates in children and young adults with relapsed hematological malignancies, determine the recommended phase 2 dose (RP2D) of tagraxofusp given alone and in combination with chemotherapy, as well as to describe the toxicities, pharmacokinetics, and pharmacodynamic properties of tagraxofusp in pediatric patients. About 54 children and young adults will participate in this study. Patients with Down syndrome will be included in part 1 of the study.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
67555
All
1 Year to 21 Years old
Phase 1
NCT05476770
STU-2022-1157
Inclusion Criteria:
Age
• Patients must be ≥ 1 and ≤21 years of age at the time of study enrollment. Diagnosis
• Relapsed and/or refractory hematologic malignancy (including, but not limited to, acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndrome, mixed phenotype acute leukemia, acute undifferentiated leukemia, blastic plasmacytoid dendritic cell neoplasm, Hodgkin lymphoma, and non-Hodgkin lymphoma).
• Tumor cells must demonstrate surface expression of CD123 at the time of enrollment by flow cytometry or immunohistochemistry, as defined by the local institution. Disease Status: Monotherapy, Part 1
• Second or greater relapse; or
• Refractory after 2 or more chemotherapy cycles; or
• First relapse after primary chemotherapy-refractory disease; or
• BPDCN in first relapse or refractory after 1 or more chemotherapy cycles Combination therapy, Part 2
• First or greater relapse; or
• Refractory after 2 or more chemotherapy cycles; or
• BPDCN in first relapse or refractory after 1 or more chemotherapy cycles For relapsed/refractory leukemia, patients must have:
• >5% blasts in the bone marrow aspirate by morphology or flow cytometry
• Patients with 1% - 5% blasts are eligible for Part 2, Cohort C (only), if A single bone marrow sample with flow cytometry and at least one other test (e.g. karyotype, FISH, PCR, or NGS) shows ≥ 1% leukemic blasts and/or flow cytometry demonstrates a stable or rising level of disease on two serial bone marrows. For relapsed/refractory non-Hodgkin or Hodgkin lymphoma, patients must have:
• Histologic verification of relapse
• Measurable disease documented by radiographic criteria or bone marrow
• Patients in Part 1 may have sites of non-CNS extramedullary disease, but no CNS disease. Patients in Part 2 may have CNS disease and/or other non-CNS extramedullary disease. No cranial irradiation is allowed during the protocol therapy.
• Patients with Down syndrome are eligible. Performance Level
• Karnofsky > 50% for patients > 16 years of age and Lansky > 50% for patients ≤ 16 years of age (See Appendix I for Performance Scales). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. Prior Therapy
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy, defined as resolution of all such toxicities to ≤ Grade 2 or lower per the inclusion/exclusion criteria. Myelosuppressive chemotherapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. At least 14 day must have elapsed since the completion of myelosuppressive therapy. However, individuals may receive any of the following medications within 14 days without a "wash-out period":
• Hydroxyurea: Hydroxyurea can be initiated and/or continued for up to 24 hours prior to the start of protocol therapy.
• "Maintenance-style" therapy: therapy including vincristine (dosed a maximum of one-time weekly), oral 6-mercaptopurine, oral methotrexate (dosed a maximum of one-time weekly), intrathecal therapy (dosed a maximum of one-time weekly) and/or dexamethasone (dosed at ≤3 mg/m2/dose twice daily) or prednisone (dosed at ≤20 mg/m2/dose twice daily) can be continued for up to 24 hours prior to entering the study.
• Hematopoietic stem cell transplant: Patients who have experienced their relapse after a HSCT are eligible, provided they have no evidence of acute or chronic Graft-versus-Host Disease (GVHD) and are at least 100 days post-transplant at the time of enrollment.
• Hematopoietic growth factors: It must have been at least 7 days since the completion of therapy with granulocyte colony stimulating factor (GCSF) or other growth factors at the time of enrollment. It must have been at least 14 days since the completion of therapy with pegfilgrastim (Neulasta®).
• Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair.
• Monoclonal antibodies: Maximum of 3 half-lives of the antibody or 21 days (whichever is shorter) must have elapsed after the last dose of monoclonal antibody.
• Immunotherapy: At least 30 days from last infusion of chimeric antigen receptor T cell (CART) therapy or tumor vaccine.
• XRT: Craniospinal XRT is prohibited during protocol therapy. No washout period is necessary for radiation given to any extramedullary site other than CNS chloromas; ≥ 90 days must have elapsed if prior TBI or craniospinal XRT.
• Patients that have received other non-tagraxofusp CD123 targeting agents are eligible. Patients that have previously received tagraxofusp are not eligible. Organ Function Requirements Adequate Bone Marrow Function Defined as:
• Patients should not be known to be refractory to red blood cell or platelet transfusions.
• Blood counts are not required to be normal prior to enrollment on trial. However, platelet count must be ≥20,000/mm3 to initiate therapy (may receive platelet transfusions). Adequate Renal Function Defined as:
• Patient must have a calculated creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73m2 OR a normal serum creatinine based on age/gender in the chart below: Maximum Serum Creatinine (mg/dL):
• 1 to < 2 years old - Male: 0.6, Female: 0.6
• 2 to < 6 years old - Male:0.8, Female: 0.8
• 6 to < 10 years old - Male: 1, Female: 1
• 10 to < 13 years old - Male: 1.2, Female: 1.2
• 13 to < 16 years old - Male: 1.5, Female: 1.4
• ≥ 16 years old - Male: 1.7, Female: 1.4 The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the CDC. Adequate Liver Function Defined as:
• Total bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x institutional upper limit of normal for age
• SGPT (ALT) and SGOT (AST) must be less than 3x institutional upper limit of normal.
• Serum albumin ≥3.2 g/dL (albumin infusion independent). Adequate Cardiac Function Defined as:
• Shortening fraction of ≥27% by echocardiogram, or
• Ejection fraction of ≥ 50% by gated radionuclide study/echocardiogram. Adequate Pulmonary Function Defined as:
• Pulse oximetry > 94% on room air (> 90% if at high altitude)
• No evidence of dyspnea at rest and no exercise intolerance. Reproductive Function
• Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed within 2 weeks prior to enrollment.
• Female patients with infants must agree not to breastfeed their infants while on this study.
• Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study and for 12 weeks after the last dose of tagraxofusp. Exclusion Criteria Disease Status:
• Patients with CNS disease are not eligible for Part 1.
• Patients with isolated CNS disease are not eligible for Part 1 or Part 2.
• Patients with isolated non-CNS disease are eligible for Part 1 and Part 2. Concomitant Medications
• Corticosteroids - Patients receiving corticosteroids for disease control who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible.
• Investigational Drugs - Patients who are currently receiving another investigational drug are not eligible. The definition of "investigational" for use in this protocol means any drug that is not licensed by the FDA, Health Canada or the Therapeutic Goods Administration to be sold in the countries they govern. (United States, Canada and Australia)
• Anti-cancer Agents - Patients who are currently receiving or may receive while on therapy, other anti-cancer agents, radiation therapy or immunotherapy are not eligible [except hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy]. Intrathecal chemotherapy (at the discretion of the primary oncologist) may be given up to one week prior to the initiation of study treatment (day 1 therapy).
• Anti-GVHD or agents to prevent organ rejection post-transplant - Patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial. At least 4 weeks must have elapsed after the last dose of GVHD meds. Infection Criteria - Patients are excluded if they have:
• Positive blood culture within 48 hours of study enrollment;
• Fever above 38.2 within 48 hours of study enrollment with clinical signs of infection. Fever that is determined to be due to tumor burden is allowed if patients have documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability.
• A positive fungal culture within 30 days of study enrollment.
• Active fungal, viral, bacterial, or protozoal infection requiring IV treatment. Chronic prophylaxis therapy to prevent infections is allowed.
• Patients will be excluded if they have a known allergy to any of the drugs used in the study.
• Patients will be excluded if they have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results.
• Patients with DNA fragility syndromes (such as Fanconi anemia, Bloom syndrome) are excluded.
Drug: Tagraxofusp, Drug: Fludarabine, Drug: Cytarabine, Drug: Dexamethasone, Drug: Vincristine, Drug: Azacitidine, Drug: Methotrexate, Drug: Cytarabine IT, Drug: Hydrocortisone
Lymphoma, B-cell, Hodgkin Lymphoma, Acute Undifferentiated Leukemia, MDS, Lymphoblastic Lymphoma, Mixed Phenotype Acute Leukemia, AML, Leukemia, Other, Hodgkins Lymphoma, Leukemia, Not Otherwise Specified, Myeloid and Monocytic Leukemia, Non-Hodgkins Lymphoma, ALL, Hematologic Malignancy, BPDCN, Lymphoma, T-Cell
Children’s Health