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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2024-01994 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| AALL2321 | Other Identifier | Children's Oncology Group | |
| AALL2321 | Other Identifier | CTEP | |
| U10CA180886 | U.S. NIH Grant/Contract | View source |
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This phase II trial tests the addition of venetoclax and/or blinatumomab to usual chemotherapy for treating infants with newly diagnosed acute lymphoblastic leukemia (ALL) with a KMT2A gene rearrangement (KMT2A-rearranged [R]) or without a KMT2A gene rearrangement (KMT2A-germline [G]). Venetoclax is in a class of medications called B-cell lymphoma-2 (Bcl-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Blinatumomab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs 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. Adding venetoclax and/or blinatumomab to standard chemotherapy may be more effective at treating patients with ALL than standard chemotherapy alone, but it may also cause more side effects. This clinical trial evaluates the safety and effectiveness of adding venetoclax and/or blinatumomab to chemotherapy for the treatment of infants with KMT2A-R or KMT2A-G ALL.
PRIMARY OBJECTIVES:
I. To evaluate the safety and tolerability of venetoclax in addition to a standard chemotherapy backbone and two cycles of blinatumomab in infants (aged 365 days or less at diagnosis) with newly diagnosed KMT2A-R ALL.
II. To determine in a randomized manner if the addition of venetoclax to induction chemotherapy improves end of induction minimal residual disease (MRD)-negative remission rates in infants with KMT2A-R ALL.
SECONDARY OBJECTIVES:
I. To estimate the MRD-negative remission rate for all eligible infants with KMT2A-R ALL treated with venetoclax at the recommended phase 2 dose (RP2D).
II. To compare event free survival (EFS) rates of infants with KMT2A-R ALL treated on arm B to those treated on arm A.
III. To compare 3-year EFS rates of infants with KMT2A-R ALL treated on arm A to historical controls.
IV. To determine the feasibility of treating infants with KMT2A-G ALL with a Children's Oncology Group (COG) high risk ALL chemotherapy backbone and two cycles of blinatumomab and estimate the 3-year EFS rate of infants with KMT2A-G ALL treated on arm C.
V. To characterize the pharmacokinetics (PK) of venetoclax in infants.
EXPLORATORY OBJECTIVES:
I. To describe 3-year EFS rate of infants with KMT2A-R ALL treated on arm B. II. To evaluate the use of high-throughput sequencing (HTS) for MRD detection in infant ALL compared to centralized flow cytometry.
III. To characterize the PK of calaspargase pegol-mknl in infants with ALL. IV. To report the incidence of CD19 negative relapse and myeloid switch relapse with protocol therapy.
V. To evaluate the impact of venetoclax in combination with chemotherapy on T-cell subsets and function.
VI. To describe the feasibility of T-cell collection and success of T-cell manufacturing for infants with KMT2A-R ALL who receive chimeric antigen receptor (CAR) T- cell therapy after coming off protocol therapy.
VII. To determine predictors of response and resistance to venetoclax and overall protocol therapy.
VIII. To evaluate the impact of subsequent anti-cancer therapy on overall survival after coming off protocol therapy.
OUTLINE:
STEROID PREPHASE: All patients receive prednisone or prednisolone orally (PO) or nasogastrically (NG) three times daily (TID) or methylprednisolone intravenously (IV) TID for 7 days prior to the start of induction therapy (on days 1-7).
Patients who are KMT2A gene rearrangement positive are assigned to the safety phase cohort during the safety phase of the study, or randomized between Arm A and Arm B during the expansion phase of the study. Patients who are KMT2A gene rearrangement negative are assigned to Arm C.
SAFETY PHASE COHORT:
INDUCTION: Patients receive venetoclax PO or NG once daily (QD) on days 1-7, 1-10, or 1-14, daunorubicin IV over 1-15 minutes on days 1 and 2, vincristine IV on days 1, 8, 15, and 22, dexamethasone PO, NG, or IV TID on days 1-28, calaspargase pegol IV over 1-2 hours on day 4, and intrathecal therapy (methotrexate, hydrocortisone, cytarabine) intrathecally (IT) on days 1, 15, and 29 or days 1, 8, 15, 22, and 29. Patients with < 5% blasts by morphology in the bone marrow at the end of induction (day 35) proceed directly to blinatumomab block 1 on the next day or when absolute neutrophil counts (ANC) >= 500/uL and platelets >= 50,000/uL. Patients with >= 5% blasts by morphology in the bone marrow at the end of induction proceed to blinatumomab block 1 as soon as marrow results are known, irrespective of ANC or platelet values.
BLINATUMOMAB BLOCK 1: Patients receive dexamethasone PO, NG, or IV on day 1 or days 1 and 8, blinatumomab IV on days 1-28, 1-7, or 8-28, and intrathecal therapy IT on days 15 and 29. Patients who are MRD >= 1% or who have residual non-central nervous system (CNS) extramedullary disease at the end of blinatumomab block 1 (day 35) discontinue protocol therapy. All other patients proceed directly to consolidation on the next day or when peripheral counts recover to ANC >= 500/uL and platelets >= 50,000/uL.
CONSOLIDATION: Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29, cytarabine subcutaneously (SC) QD or IV over 15-30 minutes on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine PO or NG QD on days 1-14 and 29-42, and intrathecal therapy IT on day 29. Patients who are MRD >= 0.01% at the end of consolidation therapy (day 56) discontinue protocol therapy. All other patients proceed directly to MARMA the next day or when peripheral counts recover to ANC >= 750/uL and platelets >= 75,000/uL.
MARMA: Patients receive mercaptopurine PO or NG QD on days 1-14, high dose methotrexate IV over 24 hours on days 1 and 8, leucovorin PO, NG, or IV or levoleucovorin IV on days 3-4 and 10-11, intrathecal therapy IT on days 1 and 8, high dose cytarabine IV over 3 hours on days 22-23 and 29-30, and recombinant crisantaspase IM or crisantaspase IM or IV over 1-2 hours on days 23 and 30. At the end of MARMA (day 49), all patients proceed directly to blinatumomab block 2 the next day or when peripheral counts recover to ANC >= 500/uL and platelets >= 50,000/uL.
BLINATUMOMAB BLOCK 2: Patients receive blinatumomab IV on days 1-28 and intrathecal therapy IT on days 1 and 15. At the end of blinatumomab block 2 (day 35), all patients proceed directly to delayed intensification the next day or when peripheral counts recover to ANC >= 750/uL and platelets >= 75,000/uL.
DELAYED INTENSIFICATION: Patients receive calaspargase pegol IV over 1-2 hours on day 1, dexamethasone PO, NG, or IV TID on days 1-21, thioguanine PO or NG on days 1-28 and 36-49, vincristine IV on days 1, 8, 15, and 22, daunorubicin IV over 1-15 minutes on days 1, 8, 15, and 22, cytarabine SC or IV over 15-30 minutes on days 2-5, 9-12, 16-19, 23-26, 37-40, and 44-47, cyclophosphamide IV over 15-30 minutes on days 36 and 50, and intrathecal therapy IT on days 1 and 15. At the end of delayed intensification (day 63), all patients proceed directly to maintenance the next day or when peripheral counts recover to ANC >= 500/uL and platelets >= 50,000/uL.
MAINTENANCE: Patients receive mercaptopurine PO or NG on days 1-84 of each cycle, methotrexate PO, NG, or IV on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 of each cycle, and intrathecal therapy IT on day 1 of cycles 1-3. Cycles repeat every 12 weeks (84 days) for up to 2 years from the start of MARMA in the absence of disease progression or unacceptable toxicity.
EXPANSION PHASE: After completion of Safety phase, patients who are KMT2A gene rearrangement positive are randomized to Arm A or Arm B.
ARM A:
INDUCTION: Patients receive daunorubicin IV over 1-15 minutes on days 1 and 2, cytarabine SC or IV over 15-30 minutes on days 1-14, vincristine IV on days 1, 8, 15, and 22, dexamethasone PO, NG, or IV TID on days 1-28, calaspargase pegol IV over 1-2 hours on day 4, and intrathecal therapy IT on days 1, 15, and 29, or days 1, 8, 15, 22, and 29. Patients with < 5% blasts by morphology in the bone marrow at the end of induction (day 35) proceed directly to blinatumomab block 1 on the next day or when ANC >= 500/uL and platelets >= 50,000/uL. Patients with >= 5% blasts by morphology in the bone marrow at the end of induction proceed to blinatumomab block 1 as soon as marrow results are known, irrespective of ANC or platelet values.
BLINATUMOMAB BLOCK 1: Patients receive dexamethasone PO, NG, or IV on day 1 or days 1 and 8, blinatumomab IV on days 1-28, 1-7, or 8-28, and intrathecal therapy IT on days 15 and 29. Patients who are MRD >= 1% or who have residual non-CNS extramedullary disease at the end of blinatumomab block 1 (day 35) discontinue protocol therapy. All other patients proceed directly to consolidation on the next day or when peripheral counts recover to ANC >= 500/uL and platelets >= 50,000/uL.
CONSOLIDATION: Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29, cytarabine SC QD or IV over 15-30 minutes on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine PO or NG QD on days 1-14 and 29-42, and intrathecal therapy IT on day 29. Patients who are MRD >= 0.01% at the end of consolidation therapy (day 56) discontinue protocol therapy. All other patients proceed directly to MARMA the next day or when peripheral counts recover to ANC >= 750/uL and platelets >= 75,000/uL.
MARMA: Patients receive mercaptopurine PO or NG QD on days 1-14, high dose methotrexate IV over 24 hours on days 1 and 8, leucovorin PO, NG, or IV or levoleucovorin IV on days 3-4 and 10-11, intrathecal therapy IT on days 1 and 8, high dose cytarabine IV over 3 hours on days 22-23 and 29-30, and recombinant crisantaspase IM or crisantaspase IM or IV over 1-2 hours on days 23 and 30. At the end of MARMA (day 49), all patients proceed directly to blinatumomab block 2 the next day or when peripheral counts recover to ANC >= 500/uL and platelets >= 50,000/uL.
BLINATUMOMAB BLOCK 2: Patients receive blinatumomab IV on days 1-28 and intrathecal therapy IT on days 1 and 15. At the end of blinatumomab block 2 (day 35), all patients proceed directly to delayed intensification the next day or when peripheral counts recover to ANC >= 750/uL and platelets >= 75,000/uL.
DELAYED INTENSIFICATION: Patients receive calaspargase pegol IV over 1-2 hours on day 1, dexamethasone PO, NG, or IV TID on days 1-21, thioguanine PO or NG on days 1-28 and 36-49, vincristine IV on days 1, 8, 15, and 22, daunorubicin IV over 1-15 minutes on days 1, 8, 15, and 22, cytarabine SC or IV over 15-30 minutes on days 2-5, 9-12, 16-19, 23-26, 37-40, and 44-47, cyclophosphamide IV over 15-30 minutes on days 36 and 50, and intrathecal therapy IT on days 1 and 15. At the end of delayed intensification (day 63), all patients proceed directly to maintenance the next day or when peripheral counts recover to ANC >= 500/uL and platelets >= 50,000/uL.
MAINTENANCE: Patients receive mercaptopurine PO or NG on days 1-84 of each cycle, methotrexate PO, NG, or IV on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 of each cycle, and intrathecal therapy IT on day 1 of cycles 1-3. Cycles repeat every 12 weeks (84 days) for up to 2 years from the start of MARMA in the absence of disease progression or unacceptable toxicity.
ARM B: Patients are assigned to 1 of 4 cohorts.
COHORT 1:
INDUCTION + VENETOCLAX: Patients receive venetoclax PO or NG QD, daunorubicin IV over 1-15 minutes on days 1 and 2, vincristine IV on days 1, 8, 15, and 22, dexamethasone PO, NG, or IV TID on days 1-28, calaspargase pegol IV over 1-2 hours on day 4, and intrathecal therapy IT on days 1, 15, and 29 or days 1, 8, 15, 22, and 29. Patients with < 5% blasts by morphology in the bone marrow at the end of induction (day 35) proceed directly to blinatumomab block 1 on the next day or when ANC >= 500/uL and platelets >= 50,000/uL. Patients with >= 5% blasts by morphology in the bone marrow at the end of induction proceed to blinatumomab block 1 as soon as marrow results are known, irrespective of ANC or platelet values.
BLINATUMOMAB BLOCK 1: Patients receive dexamethasone PO, NG, or IV on day 1 or days 1 and 8, blinatumomab IV on days 1-28, 1-7, or 8-28, and intrathecal therapy IT on days 15 and 29. Patients who are MRD >= 1% or who have residual non-CNS extramedullary disease at the end of blinatumomab block 1 (day 35) discontinue protocol therapy. All other patients proceed directly to consolidation on the next day or when peripheral counts recover to ANC >= 500/uL and platelets >= 50,000/uL.
CONSOLIDATION: Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29, cytarabine SC QD or IV over 15-30 minutes on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine PO or NG QD on days 1-14 and 29-42, and intrathecal therapy IT on day 29. Patients who are MRD >= 0.01% at the end of consolidation therapy (day 56) discontinue protocol therapy. All other patients proceed directly to MARMA the next day or when peripheral counts recover to ANC >= 750/uL and platelets >= 75,000/uL.
MARMA + VENETOCLAX: Patients receive mercaptopurine PO or NG QD on days 1-14, high dose methotrexate IV over 24 hours on days 1 and 8, leucovorin PO, NG, or IV or levoleucovorin IV on days 3-4 and 10-11, intrathecal therapy IT on days 1 and 8, venetoclax PO or NG QD, high dose cytarabine IV over 3 hours on days 22-23 and 29-30, and recombinant crisantaspase IM or crisantaspase IM or IV over 1-2 hours on days 23 and 30. At the end of MARMA (day 49), all patients proceed directly to blinatumomab block 2 the next day or when peripheral counts recover to ANC >= 500/uL and platelets >= 50,000/uL.
BLINATUMOMAB BLOCK 2: Patients receive blinatumomab IV on days 1-28 and intrathecal therapy IT on days 1 and 15. At the end of blinatumomab block 2 (day 35), all patients proceed directly to delayed intensification the next day or when peripheral counts recover to ANC >= 750/uL and platelets >= 75,000/uL.
DELAYED INTENSIFICATION: Patients receive calaspargase pegol IV over 1-2 hours on day 1, dexamethasone PO, NG, or IV TID on days 1-21, thioguanine PO or NG on days 1-28 and 36-49, vincristine IV on days 1, 8, 15, and 22, daunorubicin IV over 1-15 minutes on days 1, 8, 15, and 22, cytarabine SC or IV over 15-30 minutes on days 2-5, 9-12, 16-19, 23-26, 37-40, and 44-47, cyclophosphamide IV over 15-30 minutes on days 36 and 50, and intrathecal therapy IT on days 1 and 15. At the end of delayed intensification (day 63), all patients proceed directly to maintenance the next day or when peripheral counts recover to ANC >= 500/uL and platelets >= 50,000/uL.
MAINTENANCE: Patients receive mercaptopurine PO or NG on days 1-84 of each cycle, methotrexate PO, NG, or IV on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 of each cycle, and intrathecal therapy IT on day 1 of cycles 1-3. Cycles repeat every 12 weeks (84 days) for up to 2 years from the start of MARMA in the absence of disease progression or unacceptable toxicity.
COHORT 2:
INDUCTION + VENETOCLAX: Patients receive venetoclax PO or NG QD, daunorubicin IV over 1-15 minutes on days 1 and 2, vincristine IV on days 1, 8, 15, and 22, dexamethasone PO, NG, or IV TID on days 1-28, calaspargase pegol IV over 1-2 hours on day 4, and intrathecal therapy IT on days 1, 15, and 29 or days 1, 8, 15, 22, and 29. Patients with < 5% blasts by morphology in the bone marrow at the end of induction (day 35) proceed directly to blinatumomab block 1 on the next day or when ANC >= 500/uL and platelets >= 50,000/uL. Patients with >= 5% blasts by morphology in the bone marrow at the end of induction proceed to blinatumomab block 1 as soon as marrow results are known, irrespective of ANC or platelet values.
BLINATUMOMAB BLOCK 1: Patients receive dexamethasone PO, NG, or IV on day 1 or days 1 and 8, blinatumomab IV on days 1-28, 1-7, or 8-28, and intrathecal therapy IT on days 15 and 29. Patients who are MRD >= 1% or who have residual non-CNS extramedullary disease at the end of blinatumomab block 1 (day 35) discontinue protocol therapy. All other patients proceed directly to consolidation on the next day or when peripheral counts recover to ANC >= 500/uL and platelets >= 50,000/uL.
CONSOLIDATION + VENETOCLAX: Patients receive venetoclax PO or NG QD, cyclophosphamide IV over 30-60 minutes on days 1 and 29, cytarabine SC QD or IV over 15-30 minutes on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine PO or NG QD on days 1-14 and 29-42, and intrathecal therapy IT on day 29. Patients who are MRD >= 0.01% at the end of consolidation therapy (day 56) discontinue protocol therapy. All other patients proceed directly to MARMA the next day or when peripheral counts recover to ANC >= 750/uL and platelets >= 75,000/uL.
MARMA: Patients receive mercaptopurine PO or NG QD on days 1-14, high dose methotrexate IV over 24 hours on days 1 and 8, leucovorin PO, NG, or IV or levoleucovorin IV on days 3-4 and 10-11, intrathecal therapy IT on days 1 and 8, high dose cytarabine IV over 3 hours on days 22-23 and 29-30, and recombinant crisantaspase IM or crisantaspase IM or IV over 1-2 hours on days 23 and 30. At the end of MARMA (day 49), all patients proceed directly to blinatumomab block 2 the next day or when peripheral counts recover to ANC >= 500/uL and platelets >= 50,000/uL.
BLINATUMOMAB BLOCK 2: Patients receive blinatumomab IV on days 1-28 and intrathecal therapy IT on days 1 and 15. At the end of blinatumomab block 2 (day 35), all patients proceed directly to delayed intensification the next day or when peripheral counts recover to ANC >= 750/uL and platelets >= 75,000/uL.
DELAYED INTENSIFICATION: Patients receive calaspargase pegol IV over 1-2 hours on day 1, dexamethasone PO, NG, or IV TID on days 1-21, thioguanine PO or NG on days 1-28 and 36-49, vincristine IV on days 1, 8, 15, and 22, daunorubicin IV over 1-15 minutes on days 1, 8, 15, and 22, cytarabine SC or IV over 15-30 minutes on days 2-5, 9-12, 16-19, 23-26, 37-40, and 44-47, cyclophosphamide IV over 15-30 minutes on days 36 and 50, and intrathecal therapy IT on days 1 and 15. At the end of delayed intensification (day 63), all patients proceed directly to maintenance the next day or when peripheral counts recover to ANC >= 500/uL and platelets >= 50,000/uL.
MAINTENANCE: Patients receive mercaptopurine PO or NG on days 1-84 of each cycle, methotrexate PO, NG, or IV on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 of each cycle, and intrathecal therapy IT on day 1 of cycles 1-3. Cycles repeat every 12 weeks (84 days) for up to 2 years from the start of MARMA in the absence of disease progression or unacceptable toxicity.
COHORT 3:
INDUCTION + VENETOCLAX: Patients receive venetoclax PO or NG QD, daunorubicin IV over 1-15 minutes on days 1 and 2, vincristine IV on days 1, 8, 15, and 22, dexamethasone PO, NG, or IV TID on days 1-28, calaspargase pegol IV over 1-2 hours on day 4, and intrathecal therapy IT on days 1, 15, and 29 or days 1, 8, 15, 22, and 29. Patients with < 5% blasts by morphology in the bone marrow at the end of induction (day 35) proceed directly to blinatumomab block 1 on the next day or when ANC >= 500/uL and platelets >= 50,000/uL. Patients with >= 5% blasts by morphology in the bone marrow at the end of induction proceed to blinatumomab block 1 as soon as marrow results are known, irrespective of ANC or platelet values.
BLINATUMOMAB BLOCK 1: Patients receive dexamethasone PO, NG, or IV on day 1 or days 1 and 8, blinatumomab IV on days 1-28, 1-7, or 8-28, and intrathecal therapy IT on days 15 and 29. Patients who are MRD >= 1% or who have residual non-CNS extramedullary disease at the end of blinatumomab block 1 (day 35) discontinue protocol therapy. All other patients proceed directly to consolidation on the next day or when peripheral counts recover to ANC >= 500/uL and platelets >= 50,000/uL.
CONSOLIDATION + VENETOCLAX: Patients receive venetoclax PO or NG QD, cyclophosphamide IV over 30-60 minutes on days 1 and 29, cytarabine SC QD or IV over 15-30 minutes on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine PO or NG QD on days 1-14 and 29-42, and intrathecal therapy IT on day 29. Patients who are MRD >= 0.01% at the end of consolidation therapy (day 56) discontinue protocol therapy. All other patients proceed directly to MARMA the next day or when peripheral counts recover to ANC >= 750/uL and platelets >= 75,000/uL.
MARMA + VENETOCLAX: Patients receive mercaptopurine PO or NG QD on days 1-14, high dose methotrexate IV over 24 hours on days 1 and 8, leucovorin PO, NG, or IV or levoleucovorin IV on days 3-4 and 10-11, intrathecal therapy IT on days 1 and 8, venetoclax PO or NG QD, high dose cytarabine IV over 3 hours on days 22-23 and 29-30, and recombinant crisantaspase IM or crisantaspase IM or IV over 1-2 hours on days 23 and 30. At the end of MARMA (day 49), all patients proceed directly to blinatumomab block 2 the next day or when peripheral counts recover to ANC >= 500/uL and platelets >= 50,000/uL.
BLINATUMOMAB BLOCK 2: Patients receive blinatumomab IV on days 1-28 and intrathecal therapy IT on days 1 and 15. At the end of blinatumomab block 2 (day 35), all patients proceed directly to delayed intensification the next day or when peripheral counts recover to ANC >= 750/uL and platelets >= 75,000/uL.
DELAYED INTENSIFICATION: Patients receive calaspargase pegol IV over 1-2 hours on day 1, dexamethasone PO, NG, or IV TID on days 1-21, thioguanine PO or NG on days 1-28 and 36-49, vincristine IV on days 1, 8, 15, and 22, daunorubicin IV over 1-15 minutes on days 1, 8, 15, and 22, cytarabine SC or IV over 15-30 minutes on days 2-5, 9-12, 16-19, 23-26, 37-40, and 44-47, cyclophosphamide IV over 15-30 minutes on days 36 and 50, and intrathecal therapy IT on days 1 and 15. At the end of delayed intensification (day 63), all patients proceed directly to maintenance the next day or when peripheral counts recover to ANC >= 500/uL and platelets >= 50,000/uL.
MAINTENANCE: Patients receive mercaptopurine PO or NG on days 1-84 of each cycle, methotrexate PO, NG, or IV on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 of each cycle, and intrathecal therapy IT on day 1 of cycles 1-3. Cycles repeat every 12 weeks (84 days) for up to 2 years from the start of MARMA in the absence of disease progression or unacceptable toxicity.
COHORT 4:
INDUCTION + VENETOCLAX: Patients receive venetoclax PO or NG QD, daunorubicin IV over 1-15 minutes on days 1 and 2, vincristine IV on days 1, 8, 15, and 22, dexamethasone PO, NG, or IV TID on days 1-28, calaspargase pegol IV over 1-2 hours on day 4, and intrathecal therapy IT on days 1, 15, and 29 or days 1, 8, 15, 22, and 29. Patients with < 5% blasts by morphology in the bone marrow at the end of induction (day 35) proceed directly to blinatumomab block 1 on the next day or when ANC >= 500/uL and platelets >= 50,000/uL. Patients with >= 5% blasts by morphology in the bone marrow at the end of induction proceed to blinatumomab block 1 as soon as marrow results are known, irrespective of ANC or platelet values.
BLINATUMOMAB BLOCK 1: Patients receive dexamethasone PO, NG, or IV on day 1 or days 1 and 8, blinatumomab IV on days 1-28, 1-7, or 8-28, and intrathecal therapy IT on days 15 and 29. Patients who are MRD >= 1% or who have residual non-CNS extramedullary disease at the end of blinatumomab block 1 (day 35) discontinue protocol therapy. All other patients proceed directly to consolidation on the next day or when peripheral counts recover to ANC >= 500/uL and platelets >= 50,000/uL.
CONSOLIDATION: Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29, cytarabine SC QD or IV over 15-30 minutes on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine PO or NG QD on days 1-14 and 29-42, and intrathecal therapy IT on day 29. Patients who are MRD >= 0.01% at the end of consolidation therapy (day 56) discontinue protocol therapy. All other patients proceed directly to MARMA the next day or when peripheral counts recover to ANC >= 750/uL and platelets >= 75,000/uL.
MARMA: Patients receive mercaptopurine PO or NG QD on days 1-14, high dose methotrexate IV over 24 hours on days 1 and 8, leucovorin PO, NG, or IV or levoleucovorin IV on days 3-4 and 10-11, intrathecal therapy IT on days 1 and 8, high dose cytarabine IV over 3 hours on days 22-23 and 29-30, and recombinant crisantaspase IM or crisantaspase IM or IV over 1-2 hours on days 23 and 30. At the end of MARMA (day 49), all patients proceed directly to blinatumomab block 2 the next day or when peripheral counts recover to ANC >= 500/uL and platelets >= 50,000/uL.
BLINATUMOMAB BLOCK 2: Patients receive blinatumomab IV on days 1-28 and intrathecal therapy IT on days 1 and 15. At the end of blinatumomab block 2 (day 35), all patients proceed directly to delayed intensification the next day or when peripheral counts recover to ANC >= 750/uL and platelets >= 75,000/uL.
DELAYED INTENSIFICATION: Patients receive calaspargase pegol IV over 1-2 hours on day 1, dexamethasone PO, NG, or IV TID on days 1-21, thioguanine PO or NG on days 1-28 and 36-49, vincristine IV on days 1, 8, 15, and 22, daunorubicin IV over 1-15 minutes on days 1, 8, 15, and 22, cytarabine SC or IV over 15-30 minutes on days 2-5, 9-12, 16-19, 23-26, 37-40, and 44-47, cyclophosphamide IV over 15-30 minutes on days 36 and 50, and intrathecal therapy IT on days 1 and 15. At the end of delayed intensification (day 63), all patients proceed directly to maintenance the next day or when peripheral counts recover to ANC >= 500/uL and platelets >= 50,000/uL.
MAINTENANCE: Patients receive mercaptopurine PO or NG on days 1-84 of each cycle, methotrexate PO, NG, or IV on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 of each cycle, and intrathecal therapy IT on day 1 of cycles 1-3. Cycles repeat every 12 weeks (84 days) for up to 2 years from the start of MARMA in the absence of disease progression or unacceptable toxicity.
ARM C:
INDUCTION: Patients receive daunorubicin IV over 1-15 minutes on days 1 and 2, cytarabine SC or IV over 15-30 minutes on days 1-14, vincristine IV on days 1, 8, 15, and 22, dexamethasone PO, NG, or IV TID on days 1-28, calaspargase pegol IV over 1-2 hours on day 4, and intrathecal therapy IT on days 1, 15, and 29, or days 1, 8, 15, 22, and 29. Patients with < 5% blasts by morphology in the bone marrow at the end of induction (day 35) proceed directly to blinatumomab block 1 on the next day or when ANC >= 500/uL and platelets >= 50,000/uL. Patients with >= 5% blasts by morphology in the bone marrow at the end of induction proceed to blinatumomab block 1 as soon as marrow results are known, irrespective of ANC or platelet values.
BLINATUMOMAB BLOCK 1: Patients receive dexamethasone PO, NG, or IV on day 1 or days 1 and 8, blinatumomab IV on days 1-28, 1-7, or 8-28, and methotrexate IT on days 15 and 29. Patients who are MRD >= 1% or who have residual non-CNS extramedullary disease at the end of blinatumomab block 1 (day 35) discontinue protocol therapy. All other patients proceed directly to consolidation on the next day or when peripheral counts recover to ANC >= 750/uL and platelets >= 75,000/uL.
CONSOLIDATION: Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29, cytarabine SC QD or IV over 15-30 minutes on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine PO or NG QD on days 1-14 and 29-42, methotrexate IT on days 8, 15, and 22, vincristine IV on days 15, 22, 43, and 50, and calaspargase pegol IV over 1-2 hours on days 15 and 43. Patients who are MRD >= 0.01% at the end of consolidation therapy (day 56) discontinue protocol therapy. All other patients proceed directly to interim maintenance 1 the next day or when peripheral counts recover to ANC >= 750/uL and platelets >= 75,000/uL.
INTERIM MAINTENANCE 1: Patients receive vincristine IV on days 1, 15, 29, and 43, high dose methotrexate IV over 24 hours on days 1, 15, 29, and 43, mercaptopurine PO or NG on days 1-14, 15-28, 29-42, and 43-56, methotrexate IT on days 1 and 29, and leucovorin PO or NG or IV or levoleucovorin IV on days 3-4, 17-18, 31-32, and 45-46. At the end of interim maintenance 1 (day 63), all patients proceed directly to blinatumomab block 2 the next day or when peripheral counts recover to ANC >= 500/uL and platelets >= 50,000/uL.
BLINATUMOMAB BLOCK 2: Patients receive blinatumomab IV on days 1-28, and methotrexate IT on days 1 and 15. At the end of blinatumomab block 2 (day 35), all patients proceed directly to delayed intensification the next day or when peripheral counts recover to ANC >= 750/uL and platelets >= 75,000/uL.
DELAYED INTENSIFICATION: Patients receive methotrexate IT on days 1, 29, and 36, dexamethasone PO, NG, or IV TID on days 1-7 and 15-21, vincristine IV on days 1, 8, 15, 43, and 50, doxorubicin IV over 3-15 minutes on days 1, 8, and 15, calaspargase pegol IV over 1-2 hours on days 4 and 43, cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO or NG on days 29-42, and cytarabine SC or IV over 15-30 minutes on days 29-32 and 36-39. At the end of delayed intensification (day 63), all patients proceed directly to interim maintenance 2 the next day or when peripheral counts recover to ANC >= 750/uL and platelets >= 75,000/uL.
INTERIM MAINTENANCE 2: Patients receive vincristine IV on days 1, 11, 21, 31, and 41, methotrexate IV push over 2-5 minutes of IV over 10-15 minutes on days 1, 11, 21, 31, and 41, methotrexate IT on days 1 and 31, and calaspargase pegol IV over 1-2 hours on days 2 and 23. At the end of interim maintenance 2 (day 56), all patients proceed directly to maintenance the next day or when peripheral counts recover to ANC >= 750/uL and platelets >= 75,000/uL.
MAINTENANCE: Patients receive methotrexate IT on day 1 of each cycle, vincristine IV on day 1 of each cycle, prednisone or prednisolone PO or NG BID or methylprednisolone IV BID on days 1-5 of each cycle, mercaptopurine PO or NG on days 1-84 of each cycle, and methotrexate PO, NG, or IV on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 of each cycle. Cycles repeat every 12 weeks (84 days) for up to 2 years from the start of interim maintenance 1 in the absence of disease progression or unacceptable toxicity.
All patients undergo bone marrow aspiration, collection of blood samples and echocardiography (ECHO) or multigated acquisition scan (MUGA) throughout the trial. Patients may undergo computed tomography (CT), magnetic resonance imaging (MRI), fludeoxyglucose-positron emission tomography (FDG-PET), and/or lumbar puncture if clinically indicated.
After completion of study treatment, patients are followed up for up to 3 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A | Experimental | See Detailed Description for Arm A. |
|
| Arm B, Cohort 1 | Experimental | See Detailed Description for Arm B, Cohort 1. |
|
| Arm B, Cohort 2 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Asparaginase Erwinia chrysanthemi | Drug | Given recombinant crisantaspase IM or crisantaspase IM or IV |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of dose-limiting toxicities (DLTs) (safety phase) | For the safety phase, DLTs of the induction + venetoclax cycle of KMT2A-rearranged (R) patients will be assessed. | For the duration of the induction + venetoclax cycle |
| Incidence of DLTs (expansion phase) | For the expansion phase, DLTs of Arm B will be assessed and monitored for the cycles that contain venetoclax (induction, consolidation, and MARMA cycles of Arm B). | During the induction, consolidation, and MARMA cycles of Arm B |
| Minimal residual disease (MRD)-negative remission rate | The end of induction MRD-negative remission rate will be compared between Arm A and Arm B. MRD negativity is defined as achievement of complete remission and MRD < 0.01% by flow cytometry. The MRD-negative remission rate at the end of induction between Arm A and Arm B will be compared using a one-sided Z test of proportions with Type I error of 0.15. | At the end of induction |
| Measure | Description | Time Frame |
|---|---|---|
| MRD-negative remission rate | MRD-negative remission rate at the end of induction and the standard error or 95% confidence interval will be estimated among infants with KMT2A-R acute lymphoblastic leukemia (ALL) treated with venetoclax at the RP2D. This analysis will include eligible KMT2A-R patients treated with venetoclax at the RP2D in the safety phase, as well as patients randomized to Arm B and treated with venetoclax in the expansion phase. MRD negativity is defined as < 0.01% by flow cytometry. |
| Measure | Description | Time Frame |
|---|---|---|
| 3-year EFS of infants with KMT2A-R ALL treated on Arm B | Arm B, the 3-year EFS rate from date of randomization will be estimated, and will be compared to Arm A as described in the secondary objective, and to historical 3-year EFS. Comparison to historical rate will be based on a one-sample test of proportion with one-sided Type I error of 0.15. | From date of randomization to treatment failure, first documented relapse following achievement of remission-1, occurrence of a second or secondary malignant neoplasm, or death, assessed up to 3 years |
Inclusion Criteria:
All patients must be enrolled on APEC14B1 and consented to eligibility screening (part A) prior to treatment and enrollment on AALL2321
Infants (aged 365 days or less) on the date of diagnosis are eligible; infants must be > 36 weeks gestational age at the time of enrollment
Patients must have newly diagnosed B-acute lymphoblastic leukemia (B-ALL, 2017 World Health Organization [WHO] classification), also termed B-precursor ALL, or acute leukemia of ambiguous lineage (ALAL), which includes mixed phenotype acute leukemia. For patients with ALAL, the immunophenotype of the leukemia must comprise at least 50% B lineage
Exclusion Criteria:
Patients with Down Syndrome
Patients with secondary B-ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy
Patients must not have received any cytotoxic chemotherapy for either the current diagnosis of infant ALL or for any cancer diagnosis prior to the initiation of protocol therapy, with the exception of:
Steroid pretreatment:
Intrathecal cytarabine or methotrexate:
Hydroxyurea:
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
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| Name | Affiliation | Role |
|---|---|---|
| Erin H Breese | Children's Oncology Group | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital of Alabama | Recruiting | Birmingham | Alabama | 35233 | United States |
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
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| Experimental |
See Detailed Description for Arm B, Cohort 2. |
|
| Arm B, Cohort 3 | Experimental | See Detailed Description for Arm B, Cohort 3. |
|
| Arm B, Cohort 4 | Experimental | See Detailed Description for Arm B, Cohort 4. |
|
| Arm C | Experimental | See Detailed Description for Arm C. |
|
| Safety Phase Cohort | Experimental | See Detailed Description for Safety Phase Cohort. |
|
| Steroid Prephase(prednisone, prednisolone, methylprednisolone) | Experimental | All patients receive prednisone or prednisolone PO or NG TID or methylprednisolone IV TID for 7 days prior to the start of induction therapy (on days 1-7). |
|
|
| Biospecimen Collection | Procedure | Undergo collection of blood samples |
|
|
| Blinatumomab | Biological | Given IV |
|
|
| Bone Marrow Aspiration | Procedure | Undergo bone marrow aspiration |
|
| Calaspargase Pegol | Drug | Given IV |
|
|
| Computed Tomography | Procedure | Undergo CT |
|
|
| Cyclophosphamide | Drug | Given IV |
|
|
| Cytarabine | Drug | Given IT or IV |
|
|
| Daunorubicin | Drug | Given IV |
|
|
| Dexamethasone | Drug | Given PO or NG or IV |
|
|
| Doxorubicin | Drug | Given IV |
|
|
| Echocardiography Test | Procedure | Undergo ECHO |
|
|
| FDG-Positron Emission Tomography | Procedure | Undergo FDG-PET |
|
|
| Leucovorin | Drug | Given PO or NG or IV |
|
|
| Levoleucovorin | Drug | Given IV |
|
|
| Lumbar Puncture | Procedure | Undergo lumbar puncture |
|
|
| Magnetic Resonance Imaging | Procedure | Undergo MRI |
|
|
| Mercaptopurine | Drug | Given PO or NG |
|
|
| Methotrexate | Drug | Given IT or IV or PO or NG |
|
|
| Methylprednisolone | Drug | Given IV |
|
|
| Multigated Acquisition Scan | Procedure | Undergo MUGA |
|
|
| Prednisolone | Drug | Given PO or NG |
|
|
| Prednisone | Drug | Given PO or NG |
|
|
| Therapeutic Hydrocortisone | Drug | Given IT |
|
|
| Thioguanine | Drug | Given PO or NG |
|
|
| Venetoclax | Drug | Given PO or NG |
|
|
| Vincristine | Drug | Given IV |
|
|
| At the end of induction |
| Event free survival (EFS) rates of infants with KMT2A-R ALL | The EFS rates from date of randomization of Arm B will be compared to Arm A. Comparison of EFS rates between Arm A and Arm B will be based on a one-sided logrank test with Type I error of 0.15. | From date of randomization to treatment failure, first documented relapse following achievement of remission-1, occurrence of a second or secondary malignant neoplasm, or death, assessed up to 3 years |
| 3-year EFS of infants with KMT2A-R ALL | For Arm A, the 3-year EFS rate (representing a plateau rate based on the shape of EFS curves of historical data in this patient population) from the date of randomization will be compared to the stable historical 3-year EFS rate of 35% observed in AALL0631 and other international trials. | From date of randomization to treatment failure, first documented relapse following achievement of remission-1, occurrence of a second or secondary malignant neoplasm, or death, assessed up to 3 years |
| Proportion of KMT2A-germline (G) patients in Arm C who are able to receive all treatment cycles before maintenance | The feasibility of treating KMT2A-G patients with a high-risk ALL backbone and two cycles of blinatumomab (Arm C) will be assessed. Arm C treatment will be considered feasible for KMT2A-G patients if the proportion of KMT2A-G patients in Arm C who are able to receive all treatment cycles before maintenance (i.e., up to interim maintenance 2) is more than 76.8%. The proportion of patients receiving all cycles before Maintenance will be compared to 76.8% with a one-sample exact test of proportion with Type I error of 0.15. | Up to interim maintenance 2 |
| 3-year EFS of infants with KMT2A-G ALL treated on Arm C | The 3-year EFS rate from date of enrollment of KMT2A-G patients in Arm C will be estimated with the Kaplan-Meier method. | From date of enrollment to treatment failure, first documented relapse following achievement of remission-1, occurrence of a second or secondary malignant neoplasm, or death, assessed up to 3 years |
| Pharmacokinetics (PK) of venetoclax in infants | PK samples will be collected from patients enrolled in the safety phase of the study as well as from patients randomized to Arm B in the expansion phase who consent to participate, to determine the major secondary objective of characterizing the PK of venetoclax in infants. PK samples will be evaluated in batches and standard nonlinear mixed effect modeling will be used for model building and refinement of time-concentration data. After model refinement, a non-parametric bootstrap analysis will be performed reporting the 95% confidence intervals for each PK parameter. | On days 7, 10, and 14 of induction |
| Use of high-throughput sequencing (HTS) for MRD detection in infant ALL compared to centralized flow cytometry | Pre-treatment HTS clonality and HTS MRD tracking results will be collected and compared to the required centralized flow cytometry-based MRD data to evaluate the feasibility and prognostic utility of HTS MRD evaluation in the infant ALL population. | Up to 3 years |
| PK of calaspargase pegol in infants with ALL | PK of calaspargase pegol will be analyzed by monitoring asparaginase activity levels. Once a PK model is developed for calaspargase pegol, standard regression analysis will be used to describe the relationship between drug exposure and asparaginase activity. Additionally, asparaginase-associated toxicities will be described for the entire study population and correlated with activity levels when possible. The result of this analysis will be an estimation of potential optimal exposure expected to yield the maximum efficacy while limiting toxicity. These analyses will be exploratory and descriptive. | At completion of the trial, up to 3 years |
| Incidence of CD19-negative relapse and myeloid switch relapse with protocol therapy | For patients who experience relapse, will collect information regarding the immunophenotype of the leukemic blasts at time of relapse. Will report on the rate of CD19 negative relapse as well as myeloid switch relapse for all patients enrolled on study. This analysis will be exploratory and descriptive. | At the time of relapse, up to 3 years |
| Impact of venetoclax in combination with chemotherapy on T-cell subsets and function | BCL-2 inhibition is reported to alter T-cell subsets, including increased activation, enhanced cytotoxicity against leukemia cells and heightened resistance to cell death. Peripheral blood and bone marrow samples will be collected prior to and following the first course of venetoclax to evaluate effects on T-cell subsets and function following venetoclax exposure. | Prior to and following the first course of venetoclax |
| Feasibility of T-cell collection and success of T-cell manufacturing for infants with KMT2A-R ALL who receive chimeric antigen receptor (CAR) T-cell therapy | For patients that undergo T-cell collection, will collect data regarding the feasibility of T-cell collection in the context of protocol therapy. Additionally, for patients who proceed with CAR T-cell therapy after coming off protocol therapy, will collect data regarding the success of T-cell manufacturing, infusion and response to therapy in this young population, as the success of this subsequent therapy may be heavily impacted by the effect of protocol therapy on T-cell function. These analyses will be exploratory and descriptive. | After coming off protocol therapy |
| Predictors of response and resistance to venetoclax and overall protocol therapy | Will study the inter- and intra- patient variability in the expression of apoptotic proteins (e.g., BCL-2, MCL-1, BCL-XL) and apoptotic priming at diagnosis and identify changes that occur during induction therapy in relationship to venetoclax exposure. Will then determine whether the state of BCL-2 specific apoptotic priming correlates with outcome. Will also integrate genomic and molecular features (such as developmental state, signaling, epigenomic, transcriptomic, proteomic and metabolomic states) before and after venetoclax exposure, for those assays where this type of analysis is feasible, to determine biomarkers of response and resistance to therapy for infants with ALL. | Before and after venetoclax exposure, up to 3 years |
| Impact of subsequent anti-cancer therapy on overall survival | For all patients who remain in study follow-up after coming off protocol therapy, data will be collected regarding subsequent cancer directed therapies received as well as relapse and survival status in order to evaluate the impact of subsequent cancer directed therapy on the overall survival of patients enrolled on this study. These analyses will be exploratory and descriptive. | After coming off protocol therapy |
| Providence Alaska Medical Center | Recruiting | Anchorage | Alaska | 99508 | United States |
|
| Banner Children's at Desert | Recruiting | Mesa | Arizona | 85202 | United States |
|
| Arkansas Children's Hospital | Suspended | Little Rock | Arkansas | 72202-3591 | United States |
| Loma Linda University Medical Center | Recruiting | Loma Linda | California | 92354 | United States |
|
| Miller Children's and Women's Hospital Long Beach | Recruiting | Long Beach | California | 90806 | United States |
|
| UCSF Benioff Children's Hospital Oakland | Recruiting | Oakland | California | 94609 | United States |
|
| Kaiser Permanente-Oakland | Recruiting | Oakland | California | 94611 | United States |
|
| Children's Hospital of Orange County | Recruiting | Orange | California | 92868 | United States |
|
| University of California Davis Comprehensive Cancer Center | Recruiting | Sacramento | California | 95817 | United States |
|
| UCSF Medical Center-Mission Bay | Recruiting | San Francisco | California | 94158 | United States |
|
| Children's Hospital Colorado | Recruiting | Aurora | Colorado | 80045 | United States |
|
| Connecticut Children's Medical Center | Recruiting | Hartford | Connecticut | 06106 | United States |
|
| Yale University | Recruiting | New Haven | Connecticut | 06520 | United States |
|
| Alfred I duPont Hospital for Children | Recruiting | Wilmington | Delaware | 19803 | United States |
|
| Children's National Medical Center | Recruiting | Washington D.C. | District of Columbia | 20010 | United States |
|
| UF Health Cancer Institute - Gainesville | Recruiting | Gainesville | Florida | 32610 | United States |
|
| Memorial Regional Hospital/Joe DiMaggio Children's Hospital | Recruiting | Hollywood | Florida | 33021 | United States |
|
| Nemours Children's Clinic-Jacksonville | Recruiting | Jacksonville | Florida | 32207 | United States |
|
| University of Miami Miller School of Medicine-Sylvester Cancer Center | Recruiting | Miami | Florida | 33136 | United States |
|
| AdventHealth Orlando | Recruiting | Orlando | Florida | 32803 | United States |
|
| Arnold Palmer Hospital for Children | Recruiting | Orlando | Florida | 32806 | United States |
|
| Nemours Children's Hospital | Recruiting | Orlando | Florida | 32827 | United States |
|
| Nemours Children's Clinic - Pensacola | Recruiting | Pensacola | Florida | 32504 | United States |
|
| Johns Hopkins All Children's Hospital | Recruiting | St. Petersburg | Florida | 33701 | United States |
|
| Saint Joseph's Hospital/Children's Hospital-Tampa | Recruiting | Tampa | Florida | 33607 | United States |
|
| Saint Mary's Medical Center | Recruiting | West Palm Beach | Florida | 33407 | United States |
|
| Children's Healthcare of Atlanta - Arthur M Blank Hospital | Recruiting | Atlanta | Georgia | 30329 | United States |
|
| Kapiolani Medical Center for Women and Children | Recruiting | Honolulu | Hawaii | 96826 | United States |
|
| Saint Luke's Cancer Institute - Boise | Recruiting | Boise | Idaho | 83712 | United States |
|
| Lurie Children's Hospital-Chicago | Recruiting | Chicago | Illinois | 60611 | United States |
|
| University of Chicago Comprehensive Cancer Center | Recruiting | Chicago | Illinois | 60637 | United States |
|
| Advocate Children's Hospital-Oak Lawn | Recruiting | Oak Lawn | Illinois | 60453 | United States |
|
| Advocate Children's Hospital-Park Ridge | Recruiting | Park Ridge | Illinois | 60068 | United States |
|
| Southern Illinois University School of Medicine | Recruiting | Springfield | Illinois | 62702 | United States |
|
| Riley Hospital for Children | Recruiting | Indianapolis | Indiana | 46202 | United States |
|
| Blank Children's Hospital | Recruiting | Des Moines | Iowa | 50309 | United States |
|
| University of Kentucky/Markey Cancer Center | Recruiting | Lexington | Kentucky | 40536 | United States |
|
| Norton Children's Hospital | Recruiting | Louisville | Kentucky | 40202 | United States |
|
| Children's Hospital New Orleans | Recruiting | New Orleans | Louisiana | 70118 | United States |
|
| Ochsner Medical Center Jefferson | Recruiting | New Orleans | Louisiana | 70121 | United States |
|
| Maine Children's Cancer Program | Recruiting | Scarborough | Maine | 04074 | United States |
|
| Sinai Hospital of Baltimore | Recruiting | Baltimore | Maryland | 21215 | United States |
|
| Johns Hopkins University/Sidney Kimmel Cancer Center | Recruiting | Baltimore | Maryland | 21287 | United States |
|
| Dana-Farber Cancer Institute | Recruiting | Boston | Massachusetts | 02215 | United States |
|
| UMass Memorial Medical Center - University Campus | Recruiting | Worcester | Massachusetts | 01655 | United States |
|
| C S Mott Children's Hospital | Recruiting | Ann Arbor | Michigan | 48109 | United States |
|
| Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital | Recruiting | Grand Rapids | Michigan | 49503 | United States |
|
| Bronson Methodist Hospital | Recruiting | Kalamazoo | Michigan | 49007 | United States |
|
| University of Minnesota/Masonic Cancer Center | Recruiting | Minneapolis | Minnesota | 55455 | United States |
|
| University of Mississippi Medical Center | Recruiting | Jackson | Mississippi | 39216 | United States |
|
| Children's Mercy Hospitals and Clinics | Recruiting | Kansas City | Missouri | 64108 | United States |
|
| Washington University School of Medicine | Recruiting | St Louis | Missouri | 63110 | United States |
|
| Mercy Hospital Saint Louis | Recruiting | St Louis | Missouri | 63141 | United States |
|
| Children's Hospital and Medical Center of Omaha | Recruiting | Omaha | Nebraska | 68114 | United States |
|
| Alliance for Childhood Diseases/Cure 4 the Kids Foundation | Recruiting | Las Vegas | Nevada | 89135 | United States |
|
| Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center | Recruiting | Lebanon | New Hampshire | 03756 | United States |
|
| Hackensack University Medical Center | Recruiting | Hackensack | New Jersey | 07601 | United States |
|
| Morristown Medical Center | Recruiting | Morristown | New Jersey | 07960 | United States |
|
| Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital | Recruiting | New Brunswick | New Jersey | 08903 | United States |
|
| Saint Joseph's Regional Medical Center | Recruiting | Paterson | New Jersey | 07503 | United States |
|
| Albany Medical Center | Recruiting | Albany | New York | 12208 | United States |
|
| Roswell Park Cancer Institute | Recruiting | Buffalo | New York | 14263 | United States |
|
| The Steven and Alexandra Cohen Children's Medical Center of New York | Recruiting | New Hyde Park | New York | 11040 | United States |
|
| Laura and Isaac Perlmutter Cancer Center at NYU Langone | Recruiting | New York | New York | 10016 | United States |
|
| Memorial Sloan Kettering Cancer Center | Recruiting | New York | New York | 10065 | United States |
|
| NYP/Weill Cornell Medical Center | Recruiting | New York | New York | 10065 | United States |
|
| University of Rochester | Recruiting | Rochester | New York | 14642 | United States |
|
| State University of New York Upstate Medical University | Recruiting | Syracuse | New York | 13210 | United States |
|
| Montefiore Medical Center - Moses Campus | Recruiting | The Bronx | New York | 10467 | United States |
|
| New York Medical College | Recruiting | Valhalla | New York | 10595 | United States |
|
| UNC Lineberger Comprehensive Cancer Center | Recruiting | Chapel Hill | North Carolina | 27599 | United States |
|
| Carolinas Medical Center/Levine Cancer Institute | Recruiting | Charlotte | North Carolina | 28203 | United States |
|
| Duke University Medical Center | Recruiting | Durham | North Carolina | 27710 | United States |
|
| East Carolina University | Recruiting | Greenville | North Carolina | 27834 | United States |
|
| Wake Forest University Health Sciences | Recruiting | Winston-Salem | North Carolina | 27157 | United States |
|
| Sanford Broadway Medical Center | Recruiting | Fargo | North Dakota | 58122 | United States |
|
| Children's Hospital Medical Center of Akron | Recruiting | Akron | Ohio | 44308 | United States |
|
| Cincinnati Children's Hospital Medical Center | Recruiting | Cincinnati | Ohio | 45229 | United States |
|
| Rainbow Babies and Childrens Hospital | Recruiting | Cleveland | Ohio | 44106 | United States |
|
| Dayton Children's Hospital | Recruiting | Dayton | Ohio | 45404 | United States |
|
| ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital | Recruiting | Toledo | Ohio | 43606 | United States |
|
| University of Oklahoma Health Sciences Center | Recruiting | Oklahoma City | Oklahoma | 73104 | United States |
|
| Lehigh Valley Hospital-Cedar Crest | Recruiting | Allentown | Pennsylvania | 18103 | United States |
|
| Geisinger Medical Center | Recruiting | Danville | Pennsylvania | 17822 | United States |
|
| Children's Hospital of Philadelphia | Recruiting | Philadelphia | Pennsylvania | 19104 | United States |
|
| Children's Hospital of Pittsburgh of UPMC | Recruiting | Pittsburgh | Pennsylvania | 15224 | United States |
|
| Rhode Island Hospital | Recruiting | Providence | Rhode Island | 02903 | United States |
|
| Prisma Health Richland Hospital | Recruiting | Columbia | South Carolina | 29203 | United States |
|
| BI-LO Charities Children's Cancer Center | Recruiting | Greenville | South Carolina | 29605 | United States |
|
| Sanford USD Medical Center - Sioux Falls | Recruiting | Sioux Falls | South Dakota | 57117-5134 | United States |
|
| East Tennessee Childrens Hospital | Recruiting | Knoxville | Tennessee | 37916 | United States |
|
| Saint Jude Children's Research Hospital | Recruiting | Memphis | Tennessee | 38105 | United States |
|
| The Children's Hospital at TriStar Centennial | Recruiting | Nashville | Tennessee | 37203 | United States |
|
| Vanderbilt University/Ingram Cancer Center | Recruiting | Nashville | Tennessee | 37232 | United States |
|
| Dell Children's Medical Center of Central Texas | Recruiting | Austin | Texas | 78723 | United States |
|
| Driscoll Children's Hospital | Recruiting | Corpus Christi | Texas | 78411 | United States |
|
| Medical City Dallas Hospital | Recruiting | Dallas | Texas | 75230 | United States |
|
| UT Southwestern/Simmons Cancer Center-Dallas | Recruiting | Dallas | Texas | 75390 | United States |
|
| El Paso Children's Hospital | Recruiting | El Paso | Texas | 79905 | United States |
|
| Cook Children's Medical Center | Recruiting | Fort Worth | Texas | 76104 | United States |
|
| Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center | Recruiting | Houston | Texas | 77030 | United States |
|
| Children's Hospital of San Antonio | Recruiting | San Antonio | Texas | 78207 | United States |
|
| Methodist Children's Hospital of South Texas | Recruiting | San Antonio | Texas | 78229 | United States |
|
| University of Virginia Cancer Center | Recruiting | Charlottesville | Virginia | 22908 | United States |
|
| Children's Hospital of The King's Daughters | Recruiting | Norfolk | Virginia | 23507 | United States |
|
| VCU Massey Comprehensive Cancer Center | Recruiting | Richmond | Virginia | 23298 | United States |
|
| Carilion Children's | Recruiting | Roanoke | Virginia | 24014 | United States |
|
| Seattle Children's Hospital | Recruiting | Seattle | Washington | 98105 | United States |
|
| Providence Sacred Heart Medical Center and Children's Hospital | Recruiting | Spokane | Washington | 99204 | United States |
|
| Saint Vincent Hospital Cancer Center Green Bay | Recruiting | Green Bay | Wisconsin | 54301 | United States |
|
| Children's Hospital of Wisconsin | Recruiting | Milwaukee | Wisconsin | 53226 | United States |
|
| University Pediatric Hospital | Recruiting | San Juan | 00926 | Puerto Rico |
|
| ID | Term |
|---|---|
| D015456 | Leukemia, Biphenotypic, Acute |
| D002051 | Burkitt Lymphoma |
| ID | Term |
|---|---|
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D020031 | Epstein-Barr Virus Infections |
| D006566 | Herpesviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D014412 | Tumor Virus Infections |
| D016393 | Lymphoma, B-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
Not provided
Not provided
| ID | Term |
|---|---|
| C000718243 | asparaginase erwinia chrysanthemi recombinant |
| D001215 | Asparaginase |
| D013048 | Specimen Handling |
| C510808 | blinatumomab |
| C568788 | N,N-dicyclohexyl-isoborneol-10-sulfonamide |
| C000595188 | calaspargase pegol |
| D003520 | Cyclophosphamide |
| D003561 | Cytarabine |
| D003630 | Daunorubicin |
| D003907 | Dexamethasone |
| D002123 | Calcium Dobesilate |
| C059464 | auricularum |
| C018038 | dexamethasone acetate |
| C004180 | dexamethasone 21-phosphate |
| D004317 | Doxorubicin |
| D002955 | Leucovorin |
| D058766 | Levoleucovorin |
| D013129 | Spinal Puncture |
| D009682 | Magnetic Resonance Spectroscopy |
| D015122 | Mercaptopurine |
| C488629 | azathiopurine |
| D008727 | Methotrexate |
| C015342 | merphos |
| D008775 | Methylprednisolone |
| C052932 | exifone |
| C011906 | Medrol Veriderm |
| D011239 | Prednisolone |
| D011241 | Prednisone |
| C407664 | deltacortene |
| C036266 | prednylidene |
| D006854 | Hydrocortisone |
| D013866 | Thioguanine |
| C579720 | venetoclax |
| D014750 | Vincristine |
| ID | Term |
|---|---|
| D000581 | Amidohydrolases |
| D006867 | Hydrolases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D008919 | Investigative Techniques |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D013259 | Steroids, Fluorinated |
| D001557 | Benzenesulfonates |
| D001555 | Benzene Derivatives |
| D001190 | Arylsulfonates |
| D017739 | Arylsulfonic Acids |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D013457 | Sulfur Compounds |
| D005575 | Formyltetrahydrofolates |
| D013763 | Tetrahydrofolates |
| D005492 | Folic Acid |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D003067 | Coenzymes |
| D001706 | Biopsy |
| D003943 | Diagnostic Techniques, Neurological |
| D011677 | Punctures |
| D013812 | Therapeutics |
| D013514 | Surgical Procedures, Operative |
| D013057 | Spectrum Analysis |
| D002623 | Chemistry Techniques, Analytical |
| D013438 | Sulfhydryl Compounds |
| D011687 | Purines |
| D000630 | Aminopterin |
| D011244 | Pregnadienediols |
| D011282 | Pregnenediones |
| D011283 | Pregnenes |
| D015062 | 11-Hydroxycorticosteroids |
| D006889 | Hydroxycorticosteroids |
| D000305 | Adrenal Cortex Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D015065 | 17-Hydroxycorticosteroids |
| D014748 | Vinca Alkaloids |
| D046948 | Secologanin Tryptamine Alkaloids |
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
| D007211 | Indoles |
| D054836 | Indolizidines |
| D007212 | Indolizines |
Not provided
Not provided