A Study Testing the Combination of Dasatinib or Imatinib to Chemotherapy Treatment With Blinatumomab for Children, Adolescents, and Young Adults With Philadelphia Chromosome Positive (Ph+) or ABL-Class Philadelphia Chromosome-Like (Ph-Like) B-cell Acute Lymphoblastic Leukemia (B-ALL)
NCT ID: NCT06124157
Last Updated: 2025-11-12
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
RECRUITING
Clinical Phase
PHASE3
Total Enrollment
222 participants
Study Classification
INTERVENTIONAL
Study Start Date
2025-05-30
Study Completion Date
2030-12-01
Brief Summary
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This pilot trial assesses the effect of the combination of blinatumomab with dasatinib or imatinib and standard chemotherapy for treating patients with Philadelphia chromosome positive (Ph+) or ABL-class Philadelphia chromosome-like (Ph-like) B-Cell acute lymphoblastic leukemia (B-ALL). Blinatumomab is a bispecific antibody that binds to two different proteins-one on the surface of cancer cells and one on the surface of cells in the immune system. An antibody is a protein made by the immune system to help fight infections and other harmful processes/cells/molecules. Blinatumomab may bind to the cancer cell and a T cell (which plays a key role in the immune system's fighting response) at the same time. Blinatumomab may strengthen the immune system's ability to fight cancer cells by activating the body's own immune cells to destroy the tumor. Dasatinib and imatinib are in a class of medications called tyrosine kinase inhibitors. They work by blocking the action of an abnormal protein that signals cancer cells to multiply, which may help keep cancer cells from growing. Giving blinatumomab and dasatinib or imatinib in combination with standard chemotherapy may work better in treating patients with Ph+ or Ph-like ABL-class B-ALL than dasatinib or imatinib with chemotherapy.
Detailed Description
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PRIMARY OBJECTIVES:
I. To estimate the 3-year event free survival (EFS) of children, adolescents, and young adults \<25 years old with newly-diagnosed Ph+ (BCR::ABL1-rearranged) B- ALL who are treated with a modified Berlin-Frankfurt-Münster (mBFM) chemotherapy backbone that incorporates three cycles of blinatumomab without traditional consolidation chemotherapy in combination with continuous dasatinib.
II. To estimate the 3-year EFS of children, adolescents, and young adults \<25 years old with newly-diagnosed ABL-class Ph-like B-ALL who are treated with a modified BFM chemotherapy backbone that incorporates three cycles of blinatumomab without traditional consolidation chemotherapy in combination with continuous imatinib for those with PDGFRB gene fusions or dasatinib for those without PDGFRB gene fusions.
III. To describe the safety and toxicity profile (infections, mucositis, neurotoxicity, cytokine release syndrome, hypogammaglobulinemia, therapy delays \> 14 days, and treatment-related mortality) for patients with Ph+ or ABL-class Ph-like B-ALL treated on this novel chemo-immunotherapy backbone with continuous tyrosine kinase inhibitor (TKI).
SECONDARY OBJECTIVES:
I. To estimate the 3-year overall survival (OS) of patients with Ph+ and ABL-class Ph-like B-ALL, respectively.
II. To estimate the 3-year EFS, disease-free survival (DFS), cumulative incidence rates (CIR) of relapse, and treatment related mortality (TRM), and OS of patients with ABL-class Ph-like B-ALL stratified by their underlying ABL-class fusion subtypes.
III. To describe rates of end of consolidation (EOC)/timepoint 2 (TP2) minimal residual disease (MRD) negativity defined as \<1x10-4 or \<0.01% for patients with Ph+ B-ALL.
IV. To describe rates of EOC/TP2 MRD negativity defined as \<1x10-4 or \<0.01% for patients with ABL-class Ph-like B-ALL collectively and based on their ABL-class fusion subtypes.
EXPLORATORY OBJECTIVES:
I. To describe rates of end of induction (EOI)/timepoint 1 (TP1) bone marrow MRD negativity defined as \<1x10-4 or \<0.01% with the introduction of the relevant TKI during Induction for patients with Ph+ and ABL-class Ph-like B-ALL, respectively.
II. To describe the outcomes of patients with Ph+ and ABL-class Ph-like B-ALL who are removed from protocol therapy due to Consolidation Failure.
III. To describe the percentage of patients with Ph+ and ABL-class Ph-like B-ALL who continue TKI beyond protocol-prescribed therapy and their outcomes.
IV. To describe the impact of MRD by next-generation sequencing (NGS) at End of Consolidation on outcomes for patients with Ph+ and ABL-class Ph-like B-ALL.
V. To describe the clinical characteristics and outcomes of patients with chronic myeloid leukemia-like biology.
VI. To describe the immune function of patients with Ph+ and ABL-class Ph-like B-ALL pre- and post-blinatumomab plus TKI and correlate with treatment response.
VII. To describe the TKI levels in the plasma and cerebrospinal fluid of children with Ph+ and ABL-class Ph-like B-ALL over the treatment course and correlate with outcome VIII. To describe the impact of TKIs and high-dose methotrexate interaction and identify clinical and biologic factors influencing methotrexate clearance.
OUTLINE:
STRATUM I (PH+ B-ALL PATIENTS):
INDUCTION PART I: Patients receive induction chemotherapy on days 1-14 as per standard of care (SOC).
INDUCTION PART II: Patients receive dasatinib PO once daily (QD) on days 15-29, daunorubicin intravenously (IV) over 15 minutes on days 15 and 22, prednisolone or prednisone PO twice daily (BID) on days 15-28, vincristine IV on days 15 and 22, methotrexate intrathecally (IT) on days 15, 22, and 29, and cytarabine IT on days 18 and 25 if central nervous system (CNS)-3 at study entry.
BLINATUMOMAB BLOCK I: Patients receive dexamethasone PO or intravenously (IV) on day 1, blinatumomab IV on days 1-28, dasatinib PO on days 1-35, and methotrexate IT on days 1 and 15 over 5 weeks on study. Patients may undergo radiation therapy in 12 QD fractions.
BLINATUMOMAB BLOCK II: Patients receive dexamethasone PO or IV on day 1, blinatumomab IV on days 1-28, dasatinib PO on days 1-35, and methotrexate IT on days 1 and 15 over 5 weeks on study.
INTERIM MAINTENANCE I: Patients receive dasatinib PO QD until the end of interim maintenance I, mercaptopurine PO QD on days 1-56, vincristine IV on days 8, 22, 36, and 50, methotrexate IT on days 8 and 36, high-dose methotrexate IV over 24 hours on days 8, 22, 36 and 50, and leucovorin PO or IV on days 10, 11, 24, 25, 38, 39, 52 and 53 over 9 weeks on study.
BLINATUMOMAB BLOCK III: Patients receive blinatumomab IV on days 1-28, dasatinib PO QD on days 1-35, and methotrexate IT on day 1 over 5 weeks on study.
DELAYED INTENSIFICATION PART I: Patients receive dasatinib PO QD on days 1-28, methotrexate IT on day 1, dexamethasone PO or IV on days 1-7 and 15-21, doxorubicin IV over 15 minutes on days 1, 8, and 15, vincristine IV on days 1, 8, and 15, and pegaspargase IV or calaspargase pegol IV over 1-2 hours on day 4 over 4 weeks on study.
DELAYED INTENSIFICATION PART II: Patients receive dasatinib PO QD on day 29 until the end of delayed intensification part II, cyclophosphamide IV over 60 minutes on day 29, cytarabine IV over 30 minutes on days 29-32 and 36-39, methotrexate IT on days 29 and 36, thioguanine PO on days 29-42, pegaspargase IV or calaspargase pegol on day 43 and vincristine IV on days 43 and 50 over 5 weeks on study.
INTERIM MAINTENANCE PART II: Patients receive dasatinib PO QD on day 1 until the end of interim maintenance part II, methotrexate IV on days 1, 11, 21, 31, and 41, vincristine IV on 1, 11, 21, 31, and 41, methotrexate IT on days 1 and 31, and pegaspargase IV or calaspargase pegol IV over 1-2 hours on days 2, 22 or 23 over 8 weeks on study.
MAINTENANCE CYCLES I-II: Patients receive dasatinib PO QD on days 1-84, methotrexate IT on days 1 and 29, dexamethasone PO BID or IV on days 1-5, 29-33, and 57-61, mercaptopurine PO on days 1-84, vincristine IV on days 1, 29 and 57, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 on study.
MAINTENANCE CYCLES III AND SUBSEQUENT CYCLES: Patients receive dasatinib PO QD on days 1-84, methotrexate IT on day 1, dexamethasone PO BID or IV on days 1-5, 29-33, and 57-61, mercaptopurine PO on days 1-84, vincristine IV on days 1, 29 and 57, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 on study. Cycles repeat every 12 weeks for 2 years from the start of Induction therapy in the absence of disease progression or unacceptable toxicity.
STRATUM II (PDGFRB ABL-CLASS FUSIONS):
BLINATUMOMAB BLOCK I: Patients receive dexamethasone PO or IV on day 1, blinatumomab IV on days 1-28, imatinib PO on days 1-35, and methotrexate IT on days 1 and 15 over 5 weeks on study. Patients may undergo radiation therapy in 12 QD fractions.
BLINATUMOMAB BLOCK II: Patients receive dexamethasone PO or IV on day 1, blinatumomab IV on days 1-28, imatinib PO on days 1-35, and methotrexate IT on days 1 and 15 over 5 weeks on study.
INTERIM MAINTENANCE I: Patients receive imatinib PO QD until the end of interim maintenance I, mercaptopurine PO QD on days 1-56, vincristine IV on days 8, 22, 36, and 50, methotrexate IT on days 8 and 36, high-dose methotrexate IV over 24 hours on days 8, 22, 36 and 50, and leucovorin PO or IV on days 10, 11, 24, 25, 38, 39, 52 and 53 over 9 weeks on study.
BLINATUMOMAB BLOCK III: Patients receive blinatumomab IV on days 1-28, imatinib PO QD on days 1-35, and methotrexate IT on day 1 over 5 weeks on study.
DELAYED INTENSIFICATION PART I: Patients receive imatinib PO QD on days 1-28, methotrexate IT on day 1, dexamethasone PO or IV on days 1-7 and 15-21, doxorubicin IV over 15 minutes on days 1, 8, and 15, vincristine IV on days 1, 8, and 15, and pegaspargase IV or calaspargase pegol IV over 1-2 hours on day 4 over 9 weeks on study.
DELAYED INTENSIFICATION PART II: Patients receive imatinib PO QD on day 29 until the end of Delayed Intensification part II, cyclophosphamide IV over 30-60 minutes on day 29, cytarabine IV over 30 minutes on days 29-32 and 36-39, methotrexate IT on days 29 and 36, thioguanine PO on days 29-42, and pegaspargase IV or calaspargase pegol IV on day 43, and vincristine IV on days 43 and 50 over 5 weeks on study.
INTERIM MAINTENANCE II: Patients receive imatinib PO QD until the end of interim maintenance II, methotrexate IV and vincristine IV on days 1, 11, 21, 31 and 41, methotrexate IT on days 1 and 31, and pegaspargase IV or calaspargase pegol IV over 1-2 hours on days 2, 22 or 23 over 8 weeks on study.
MAINTENANCE CYCLES I-II: Patients receive imatinib PO QD on days 1-84, methotrexate IT on days 1 and 29, dexamethasone PO BID or IV on days 1-5, 29-33, and 57-61, mercaptopurine PO on days 1-84, vincristine IV on days 1, 29 and 57, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 on study.
MAINTENANCE CYCLES III AND SUBSEQUENT CYCLES: Patients receive imatinib PO QD on days 1-84, methotrexate IT on day 1, dexamethasone PO BID or IV on days 1-5, 29-33, and 57-61, mercaptopurine PO on days 1-84, vincristine IV on days 1, 29 and 57, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 on study. Cycles repeat every 12 weeks for 2 years from the start of Induction therapy in the absence of disease progression or unacceptable toxicity.
STRATUM III (NON-PDGFRB ABL-CLASS FUSIONS):
BLINATUMOMAB BLOCK I: Patients receive dexamethasone PO or IV on day 1, blinatumomab IV on days 1-28, dasatinib PO on days 1-35, and methotrexate IT on days 1 and 15 over 5 weeks on study. Patients may undergo radiation therapy in 12 QD fractions.
BLINATUMOMAB BLOCK II: Patients receive dexamethasone PO or IV on day 1, blinatumomab IV on days 1-28, dasatinib PO on days 1-35, and methotrexate IT on days 1 and 15 over 5 weeks on study.
INTERIM MAINTENANCE I: Patients receive dasatinib PO QD until the end of interim maintenance I, mercaptopurine PO QD on days 1-56, vincristine IV on days 8, 22, 36, and 50, methotrexate IT on days 8 and 36, high-dose methotrexate IV over 24 hours on days 8, 22, 36 and 50, and leucovorin PO or IV on days 10, 11, 24, 25, 38, 39, 52 and 53 over 9 weeks on study.
BLINATUMOMAB BLOCK III: Patients receive blinatumomab IV on days 1-28, dasatinib PO on days 1-35, and methotrexate IT on day 1 over 5 weeks on study.
DELAYED INTENSIFICATION PART I: Patients receive dasatinib PO QD on days 1-28, methotrexate IT on day 1, dexamethasone PO or IV on days 1-7 and 15-21, doxorubicin IV over 15 minutes on days 1, 8, and 15, vincristine IV on days 1, 8, and 15, and pegaspargase IV or calaspargase pegol IV over 1-2 hours on day 4 over 4 weeks on study.
DELAYED INTENSIFICATION PART II: Patients receive dasatinib PO QD and methotrexate IT on day 29 until the end of Delayed Intensification part II, cyclophosphamide IV over 30-60 minutes on day 29, cytarabine IV over 30 minutes on days 29-32 and 36-39, methotrexate IT on days 29 and 36, thioguanine PO on days 29-42, pegaspargase IV or calaspargase pegol on day 43 and vincristine IV on days 43 and 50 over 5 weeks on study.
INTERIM MAINTENANCE II: Patients receive dasatinib PO QD until the end of interim maintenance II, methotrexate IV and vincristine IV on days 1, 11, 21, 31 and 41, methotrexate IT on days 1 and 31, and pegaspargase IV or calaspargase pegol IV over 1-2 hours on days 2, 22 or 23 over 8 weeks on study.
MAINTENANCE CYCLES I-II: Patients receive dasatinib PO QD on days 1-84, methotrexate IT on days 1 and 29, dexamethasone PO BID or IV on days 1-5, 29-33, and 57-61, mercaptopurine PO on days 1-84, vincristine IV on days 1, 29 and 57, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 on study.
MAINTENANCE CYCLES III AND SUBSEQUENT CYCLES: Patients receive dasatinib PO QD on days 1-84, methotrexate IT on day 1, dexamethasone PO BID or IV on days 1-5, 29-33, and 57-61, mercaptopurine PO on days 1-84, vincristine IV on days 1, 29 and 57, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 on study. Cycles repeat every 12 weeks for 2 years from the start of Induction therapy in the absence of disease progression or unacceptable toxicity.
All patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening. Patients also undergo blood and cerebrospinal fluid (CSF) sample collection and bone marrow biopsy throughout the study and as clinically indicated on study.
I. To estimate the 3-year event free survival (EFS) of children, adolescents, and young adults \<25 years old with newly-diagnosed Ph+ (BCR::ABL1-rearranged) B- ALL who are treated with a modified Berlin-Frankfurt-Münster (mBFM) chemotherapy backbone that incorporates three cycles of blinatumomab without traditional consolidation chemotherapy in combination with continuous dasatinib.
II. To estimate the 3-year EFS of children, adolescents, and young adults \<25 years old with newly-diagnosed ABL-class Ph-like B-ALL who are treated with a modified BFM chemotherapy backbone that incorporates three cycles of blinatumomab without traditional consolidation chemotherapy in combination with continuous imatinib for those with PDGFRB gene fusions or dasatinib for those without PDGFRB gene fusions.
III. To describe the safety and toxicity profile (infections, mucositis, neurotoxicity, cytokine release syndrome, hypogammaglobulinemia, therapy delays \> 14 days, and treatment-related mortality) for patients with Ph+ or ABL-class Ph-like B-ALL treated on this novel chemo-immunotherapy backbone with continuous tyrosine kinase inhibitor (TKI).
SECONDARY OBJECTIVES:
I. To estimate the 3-year overall survival (OS) of patients with Ph+ and ABL-class Ph-like B-ALL, respectively.
II. To estimate the 3-year EFS, disease-free survival (DFS), cumulative incidence rates (CIR) of relapse, and treatment related mortality (TRM), and OS of patients with ABL-class Ph-like B-ALL stratified by their underlying ABL-class fusion subtypes.
III. To describe rates of end of consolidation (EOC)/timepoint 2 (TP2) minimal residual disease (MRD) negativity defined as \<1x10-4 or \<0.01% for patients with Ph+ B-ALL.
IV. To describe rates of EOC/TP2 MRD negativity defined as \<1x10-4 or \<0.01% for patients with ABL-class Ph-like B-ALL collectively and based on their ABL-class fusion subtypes.
EXPLORATORY OBJECTIVES:
I. To describe rates of end of induction (EOI)/timepoint 1 (TP1) bone marrow MRD negativity defined as \<1x10-4 or \<0.01% with the introduction of the relevant TKI during Induction for patients with Ph+ and ABL-class Ph-like B-ALL, respectively.
II. To describe the outcomes of patients with Ph+ and ABL-class Ph-like B-ALL who are removed from protocol therapy due to Consolidation Failure.
III. To describe the percentage of patients with Ph+ and ABL-class Ph-like B-ALL who continue TKI beyond protocol-prescribed therapy and their outcomes.
IV. To describe the impact of MRD by next-generation sequencing (NGS) at End of Consolidation on outcomes for patients with Ph+ and ABL-class Ph-like B-ALL.
V. To describe the clinical characteristics and outcomes of patients with chronic myeloid leukemia-like biology.
VI. To describe the immune function of patients with Ph+ and ABL-class Ph-like B-ALL pre- and post-blinatumomab plus TKI and correlate with treatment response.
VII. To describe the TKI levels in the plasma and cerebrospinal fluid of children with Ph+ and ABL-class Ph-like B-ALL over the treatment course and correlate with outcome VIII. To describe the impact of TKIs and high-dose methotrexate interaction and identify clinical and biologic factors influencing methotrexate clearance.
OUTLINE:
STRATUM I (PH+ B-ALL PATIENTS):
INDUCTION PART I: Patients receive induction chemotherapy on days 1-14 as per standard of care (SOC).
INDUCTION PART II: Patients receive dasatinib PO once daily (QD) on days 15-29, daunorubicin intravenously (IV) over 15 minutes on days 15 and 22, prednisolone or prednisone PO twice daily (BID) on days 15-28, vincristine IV on days 15 and 22, methotrexate intrathecally (IT) on days 15, 22, and 29, and cytarabine IT on days 18 and 25 if central nervous system (CNS)-3 at study entry.
BLINATUMOMAB BLOCK I: Patients receive dexamethasone PO or intravenously (IV) on day 1, blinatumomab IV on days 1-28, dasatinib PO on days 1-35, and methotrexate IT on days 1 and 15 over 5 weeks on study. Patients may undergo radiation therapy in 12 QD fractions.
BLINATUMOMAB BLOCK II: Patients receive dexamethasone PO or IV on day 1, blinatumomab IV on days 1-28, dasatinib PO on days 1-35, and methotrexate IT on days 1 and 15 over 5 weeks on study.
INTERIM MAINTENANCE I: Patients receive dasatinib PO QD until the end of interim maintenance I, mercaptopurine PO QD on days 1-56, vincristine IV on days 8, 22, 36, and 50, methotrexate IT on days 8 and 36, high-dose methotrexate IV over 24 hours on days 8, 22, 36 and 50, and leucovorin PO or IV on days 10, 11, 24, 25, 38, 39, 52 and 53 over 9 weeks on study.
BLINATUMOMAB BLOCK III: Patients receive blinatumomab IV on days 1-28, dasatinib PO QD on days 1-35, and methotrexate IT on day 1 over 5 weeks on study.
DELAYED INTENSIFICATION PART I: Patients receive dasatinib PO QD on days 1-28, methotrexate IT on day 1, dexamethasone PO or IV on days 1-7 and 15-21, doxorubicin IV over 15 minutes on days 1, 8, and 15, vincristine IV on days 1, 8, and 15, and pegaspargase IV or calaspargase pegol IV over 1-2 hours on day 4 over 4 weeks on study.
DELAYED INTENSIFICATION PART II: Patients receive dasatinib PO QD on day 29 until the end of delayed intensification part II, cyclophosphamide IV over 60 minutes on day 29, cytarabine IV over 30 minutes on days 29-32 and 36-39, methotrexate IT on days 29 and 36, thioguanine PO on days 29-42, pegaspargase IV or calaspargase pegol on day 43 and vincristine IV on days 43 and 50 over 5 weeks on study.
INTERIM MAINTENANCE PART II: Patients receive dasatinib PO QD on day 1 until the end of interim maintenance part II, methotrexate IV on days 1, 11, 21, 31, and 41, vincristine IV on 1, 11, 21, 31, and 41, methotrexate IT on days 1 and 31, and pegaspargase IV or calaspargase pegol IV over 1-2 hours on days 2, 22 or 23 over 8 weeks on study.
MAINTENANCE CYCLES I-II: Patients receive dasatinib PO QD on days 1-84, methotrexate IT on days 1 and 29, dexamethasone PO BID or IV on days 1-5, 29-33, and 57-61, mercaptopurine PO on days 1-84, vincristine IV on days 1, 29 and 57, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 on study.
MAINTENANCE CYCLES III AND SUBSEQUENT CYCLES: Patients receive dasatinib PO QD on days 1-84, methotrexate IT on day 1, dexamethasone PO BID or IV on days 1-5, 29-33, and 57-61, mercaptopurine PO on days 1-84, vincristine IV on days 1, 29 and 57, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 on study. Cycles repeat every 12 weeks for 2 years from the start of Induction therapy in the absence of disease progression or unacceptable toxicity.
STRATUM II (PDGFRB ABL-CLASS FUSIONS):
BLINATUMOMAB BLOCK I: Patients receive dexamethasone PO or IV on day 1, blinatumomab IV on days 1-28, imatinib PO on days 1-35, and methotrexate IT on days 1 and 15 over 5 weeks on study. Patients may undergo radiation therapy in 12 QD fractions.
BLINATUMOMAB BLOCK II: Patients receive dexamethasone PO or IV on day 1, blinatumomab IV on days 1-28, imatinib PO on days 1-35, and methotrexate IT on days 1 and 15 over 5 weeks on study.
INTERIM MAINTENANCE I: Patients receive imatinib PO QD until the end of interim maintenance I, mercaptopurine PO QD on days 1-56, vincristine IV on days 8, 22, 36, and 50, methotrexate IT on days 8 and 36, high-dose methotrexate IV over 24 hours on days 8, 22, 36 and 50, and leucovorin PO or IV on days 10, 11, 24, 25, 38, 39, 52 and 53 over 9 weeks on study.
BLINATUMOMAB BLOCK III: Patients receive blinatumomab IV on days 1-28, imatinib PO QD on days 1-35, and methotrexate IT on day 1 over 5 weeks on study.
DELAYED INTENSIFICATION PART I: Patients receive imatinib PO QD on days 1-28, methotrexate IT on day 1, dexamethasone PO or IV on days 1-7 and 15-21, doxorubicin IV over 15 minutes on days 1, 8, and 15, vincristine IV on days 1, 8, and 15, and pegaspargase IV or calaspargase pegol IV over 1-2 hours on day 4 over 9 weeks on study.
DELAYED INTENSIFICATION PART II: Patients receive imatinib PO QD on day 29 until the end of Delayed Intensification part II, cyclophosphamide IV over 30-60 minutes on day 29, cytarabine IV over 30 minutes on days 29-32 and 36-39, methotrexate IT on days 29 and 36, thioguanine PO on days 29-42, and pegaspargase IV or calaspargase pegol IV on day 43, and vincristine IV on days 43 and 50 over 5 weeks on study.
INTERIM MAINTENANCE II: Patients receive imatinib PO QD until the end of interim maintenance II, methotrexate IV and vincristine IV on days 1, 11, 21, 31 and 41, methotrexate IT on days 1 and 31, and pegaspargase IV or calaspargase pegol IV over 1-2 hours on days 2, 22 or 23 over 8 weeks on study.
MAINTENANCE CYCLES I-II: Patients receive imatinib PO QD on days 1-84, methotrexate IT on days 1 and 29, dexamethasone PO BID or IV on days 1-5, 29-33, and 57-61, mercaptopurine PO on days 1-84, vincristine IV on days 1, 29 and 57, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 on study.
MAINTENANCE CYCLES III AND SUBSEQUENT CYCLES: Patients receive imatinib PO QD on days 1-84, methotrexate IT on day 1, dexamethasone PO BID or IV on days 1-5, 29-33, and 57-61, mercaptopurine PO on days 1-84, vincristine IV on days 1, 29 and 57, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 on study. Cycles repeat every 12 weeks for 2 years from the start of Induction therapy in the absence of disease progression or unacceptable toxicity.
STRATUM III (NON-PDGFRB ABL-CLASS FUSIONS):
BLINATUMOMAB BLOCK I: Patients receive dexamethasone PO or IV on day 1, blinatumomab IV on days 1-28, dasatinib PO on days 1-35, and methotrexate IT on days 1 and 15 over 5 weeks on study. Patients may undergo radiation therapy in 12 QD fractions.
BLINATUMOMAB BLOCK II: Patients receive dexamethasone PO or IV on day 1, blinatumomab IV on days 1-28, dasatinib PO on days 1-35, and methotrexate IT on days 1 and 15 over 5 weeks on study.
INTERIM MAINTENANCE I: Patients receive dasatinib PO QD until the end of interim maintenance I, mercaptopurine PO QD on days 1-56, vincristine IV on days 8, 22, 36, and 50, methotrexate IT on days 8 and 36, high-dose methotrexate IV over 24 hours on days 8, 22, 36 and 50, and leucovorin PO or IV on days 10, 11, 24, 25, 38, 39, 52 and 53 over 9 weeks on study.
BLINATUMOMAB BLOCK III: Patients receive blinatumomab IV on days 1-28, dasatinib PO on days 1-35, and methotrexate IT on day 1 over 5 weeks on study.
DELAYED INTENSIFICATION PART I: Patients receive dasatinib PO QD on days 1-28, methotrexate IT on day 1, dexamethasone PO or IV on days 1-7 and 15-21, doxorubicin IV over 15 minutes on days 1, 8, and 15, vincristine IV on days 1, 8, and 15, and pegaspargase IV or calaspargase pegol IV over 1-2 hours on day 4 over 4 weeks on study.
DELAYED INTENSIFICATION PART II: Patients receive dasatinib PO QD and methotrexate IT on day 29 until the end of Delayed Intensification part II, cyclophosphamide IV over 30-60 minutes on day 29, cytarabine IV over 30 minutes on days 29-32 and 36-39, methotrexate IT on days 29 and 36, thioguanine PO on days 29-42, pegaspargase IV or calaspargase pegol on day 43 and vincristine IV on days 43 and 50 over 5 weeks on study.
INTERIM MAINTENANCE II: Patients receive dasatinib PO QD until the end of interim maintenance II, methotrexate IV and vincristine IV on days 1, 11, 21, 31 and 41, methotrexate IT on days 1 and 31, and pegaspargase IV or calaspargase pegol IV over 1-2 hours on days 2, 22 or 23 over 8 weeks on study.
MAINTENANCE CYCLES I-II: Patients receive dasatinib PO QD on days 1-84, methotrexate IT on days 1 and 29, dexamethasone PO BID or IV on days 1-5, 29-33, and 57-61, mercaptopurine PO on days 1-84, vincristine IV on days 1, 29 and 57, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 on study.
MAINTENANCE CYCLES III AND SUBSEQUENT CYCLES: Patients receive dasatinib PO QD on days 1-84, methotrexate IT on day 1, dexamethasone PO BID or IV on days 1-5, 29-33, and 57-61, mercaptopurine PO on days 1-84, vincristine IV on days 1, 29 and 57, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 on study. Cycles repeat every 12 weeks for 2 years from the start of Induction therapy in the absence of disease progression or unacceptable toxicity.
All patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening. Patients also undergo blood and cerebrospinal fluid (CSF) sample collection and bone marrow biopsy throughout the study and as clinically indicated on study.
Conditions
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B Acute Lymphoblastic Leukemia
Study Design
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Allocation Method
NON_RANDOMIZED
Intervention Model
PARALLEL
Primary Study Purpose
TREATMENT
Blinding Strategy
NONE
Study Groups
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Stratum I (Ph+ ALL)
See detailed description
Group Type
EXPERIMENTAL
Biospecimen Collection
Intervention Type
PROCEDURE
Undergo blood and CSF sample collection
Blinatumomab
Intervention Type
BIOLOGICAL
Receive IV
Bone Marrow Biopsy
Intervention Type
PROCEDURE
Undergo bone marrow biopsy
Calaspargase Pegol
Intervention Type
DRUG
Receive IV
Cyclophosphamide
Intervention Type
DRUG
Receive IV
Cytarabine
Intervention Type
DRUG
Receive IV or subcutaneously
Dasatinib
Intervention Type
DRUG
Receive PO
Daunorubicin
Intervention Type
DRUG
Receive IV
Doxorubicin
Intervention Type
DRUG
Receive IV
Echocardiography Test
Intervention Type
PROCEDURE
Undergo ECHO
Leucovorin
Intervention Type
DRUG
Receive PO or IV
Mercaptopurine
Intervention Type
DRUG
Receive PO
Methotrexate
Intervention Type
DRUG
Receive IT or IV or PO
Multigated Acquisition Scan
Intervention Type
PROCEDURE
Undergo MUGA
Pegaspargase
Intervention Type
DRUG
Receive IV or intramuscularly
Prednisolone
Intervention Type
DRUG
Receive PO
Prednisone
Intervention Type
DRUG
Receive PO
Vincristine
Intervention Type
DRUG
Receive IV
Stratum II (PDGFRB ABL-Class fusions)
See detailed description.
Group Type
EXPERIMENTAL
Biospecimen Collection
Intervention Type
PROCEDURE
Undergo blood and CSF sample collection
Blinatumomab
Intervention Type
BIOLOGICAL
Receive IV
Bone Marrow Biopsy
Intervention Type
PROCEDURE
Undergo bone marrow biopsy
Calaspargase Pegol
Intervention Type
DRUG
Receive IV
Cyclophosphamide
Intervention Type
DRUG
Receive IV
Cytarabine
Intervention Type
DRUG
Receive IV or subcutaneously
Daunorubicin
Intervention Type
DRUG
Receive IV
Doxorubicin
Intervention Type
DRUG
Receive IV
Echocardiography Test
Intervention Type
PROCEDURE
Undergo ECHO
Imatinib
Intervention Type
DRUG
Given PO
Leucovorin
Intervention Type
DRUG
Receive PO or IV
Mercaptopurine
Intervention Type
DRUG
Receive PO
Methotrexate
Intervention Type
DRUG
Receive IT or IV or PO
Multigated Acquisition Scan
Intervention Type
PROCEDURE
Undergo MUGA
Pegaspargase
Intervention Type
DRUG
Receive IV or intramuscularly
Prednisolone
Intervention Type
DRUG
Receive PO
Prednisone
Intervention Type
DRUG
Receive PO
Radiation Therapy
Intervention Type
RADIATION
Undergo radiation therapy
Thioguanine
Intervention Type
DRUG
Receive PO
Vincristine
Intervention Type
DRUG
Receive IV
Stratum III (non-PDGFRB ABL-Class fusions)
See detailed description.
Group Type
EXPERIMENTAL
Biospecimen Collection
Intervention Type
PROCEDURE
Undergo blood and CSF sample collection
Blinatumomab
Intervention Type
BIOLOGICAL
Receive IV
Bone Marrow Biopsy
Intervention Type
PROCEDURE
Undergo bone marrow biopsy
Calaspargase Pegol
Intervention Type
DRUG
Receive IV
Cyclophosphamide
Intervention Type
DRUG
Receive IV
Cytarabine
Intervention Type
DRUG
Receive IV or subcutaneously
Dasatinib
Intervention Type
DRUG
Receive PO
Daunorubicin
Intervention Type
DRUG
Receive IV
Doxorubicin
Intervention Type
DRUG
Receive IV
Echocardiography Test
Intervention Type
PROCEDURE
Undergo ECHO
Leucovorin
Intervention Type
DRUG
Receive PO or IV
Mercaptopurine
Intervention Type
DRUG
Receive PO
Methotrexate
Intervention Type
DRUG
Receive IT or IV or PO
Multigated Acquisition Scan
Intervention Type
PROCEDURE
Undergo MUGA
Pegaspargase
Intervention Type
DRUG
Receive IV or intramuscularly
Prednisolone
Intervention Type
DRUG
Receive PO
Prednisone
Intervention Type
DRUG
Receive PO
Radiation Therapy
Intervention Type
RADIATION
Undergo radiation therapy
Thioguanine
Intervention Type
DRUG
Receive PO
Vincristine
Intervention Type
DRUG
Receive IV
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Biospecimen Collection
Undergo blood and CSF sample collection
Intervention Type
PROCEDURE
Blinatumomab
Receive IV
Intervention Type
BIOLOGICAL
Bone Marrow Biopsy
Undergo bone marrow biopsy
Intervention Type
PROCEDURE
Calaspargase Pegol
Receive IV
Intervention Type
DRUG
Cyclophosphamide
Receive IV
Intervention Type
DRUG
Cytarabine
Receive IV or subcutaneously
Intervention Type
DRUG
Dasatinib
Receive PO
Intervention Type
DRUG
Daunorubicin
Receive IV
Intervention Type
DRUG
Doxorubicin
Receive IV
Intervention Type
DRUG
Echocardiography Test
Undergo ECHO
Intervention Type
PROCEDURE
Imatinib
Given PO
Intervention Type
DRUG
Leucovorin
Receive PO or IV
Intervention Type
DRUG
Mercaptopurine
Receive PO
Intervention Type
DRUG
Methotrexate
Receive IT or IV or PO
Intervention Type
DRUG
Multigated Acquisition Scan
Undergo MUGA
Intervention Type
PROCEDURE
Pegaspargase
Receive IV or intramuscularly
Intervention Type
DRUG
Prednisolone
Receive PO
Intervention Type
DRUG
Prednisone
Receive PO
Intervention Type
DRUG
Radiation Therapy
Undergo radiation therapy
Intervention Type
RADIATION
Thioguanine
Receive PO
Intervention Type
DRUG
Vincristine
Receive IV
Intervention Type
DRUG
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Biological Sample Collection
Biospecimen Collected
Specimen Collection
AMG 103
AMG-103
AMG103
Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody
Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103
Blincyto
MEDI 538
MEDI-538
MEDI538
MT 103
MT-103
MT103
Biopsy of Bone Marrow
Biopsy, Bone Marrow
Asparaginase (Escherichia coli Isoenzyme II), Conjugate with alpha-(((2,5-Dioxo-1-pyrrolidinyl)oxy)carbonyl)-omega-methoxypoly(oxy-1,2-ethanediyl)
Asparlas
Calaspargase Pegol-mknl
EZN-2285
SC-PEG E. Coli L-Asparaginase
Succinimidyl Carbonate Monomethoxypolyethylene Glycol E. coli L-Asparaginase
(-)-Cyclophosphamide
2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
Asta B 518
B 518
B-518
B518
Carloxan
Ciclofosfamida
Ciclofosfamide
Cicloxal
Clafen
Claphene
CP monohydrate
CTX
CYCLO-cell
Cycloblastin
Cycloblastine
Cyclophospham
Cyclophosphamid monohydrate
Cyclophosphamide Monohydrate
Cyclophosphamidum
Cyclophosphan
Cyclophosphane
Cyclophosphanum
Cyclostin
Cyclostine
Cytophosphan
Cytophosphane
Cytoxan
Fosfaseron
Genoxal
Genuxal
Ledoxina
Mitoxan
Neosar
Revimmune
Syklofosfamid
WR 138719
WR- 138719
WR-138719
WR138719
.beta.-Cytosine arabinoside
1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
1-.beta.-D-Arabinofuranosylcytosine
1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
1-Beta-D-arabinofuranosylcytosine
1.beta.-D-Arabinofuranosylcytosine
2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
Alexan
Ara-C
ARA-cell
Arabine
Arabinofuranosylcytosine
Arabinosylcytosine
Aracytidine
Aracytin
Aracytine
Beta-Cytosine Arabinoside
CHX-3311
Cytarabinum
Cytarbel
Cytosar
Cytosine Arabinoside
Cytosine-.beta.-arabinoside
Cytosine-beta-arabinoside
Erpalfa
Starasid
Tarabine PFS
U 19920
U-19920
Udicil
WR-28453
BMS 354825
BMS-354825
BMS354825
Dasatinib Hydrate
Dasatinib Monohydrate
Sprycel
Daunomycin
Daunorrubicina
DNR
Leukaemomycin C
Rubidomycin
Rubomycin C
Adriablastin
Hydroxydaunomycin
Hydroxyl Daunorubicin
Hydroxyldaunorubicin
EC
Echocardiography
Folinic acid
3H-Purine-6-thiol
6 MP
6 Thiohypoxanthine
6 Thiopurine
6-Mercaptopurine
6-Mercaptopurine Monohydrate
6-MP
6-Purinethiol
6-Thiopurine
6-Thioxopurine
6H-Purine-6-thione, 1,7-dihydro- (9CI)
7-Mercapto-1,3,4,6-tetrazaindene
Alti-Mercaptopurine
Azathiopurine
Bw 57-323H
Flocofil
Ismipur
Leukerin
Leupurin
Mercaleukim
Mercaleukin
Mercaptina
Mercaptopurinum
Mercapurin
Mern
NCI-C04886
Puri-Nethol
Purimethol
Purine, 6-mercapto-
Purine-6-thiol (8CI)
Purine-6-thiol, monohydrate
Purinethiol
Purinethol
U-4748
WR-2785
Abitrexate
Alpha-Methopterin
Amethopterin
Brimexate
CL 14377
CL-14377
Emtexate
Emthexat
Emthexate
Farmitrexat
Fauldexato
Folex
Folex PFS
Jylamvo
Lantarel
Ledertrexate
Lumexon
Maxtrex
Medsatrexate
Metex
Methoblastin
Methotrexate LPF
Methotrexate Methylaminopterin
Methotrexatum
Metotrexato
Metrotex
Mexate
Mexate-AQ
MTX
Novatrex
Rheumatrex
Texate
Tremetex
Trexeron
Trixilem
WR-19039
Blood Pool Scan
Equilibrium Radionuclide Angiography
Gated Blood Pool Imaging
Gated Heart Pool Scan
MUGA
MUGA Scan
Multi-Gated Acquisition Scan
Radionuclide Ventriculogram Scan
Radionuclide Ventriculography
RNV Scan
RNVG
SYMA Scanning
Synchronized Multigated Acquisition Scanning
L-Asparaginase with Polyethylene Glycol
Oncaspar
Oncaspar-IV
PEG-Asparaginase
PEG-L-Asparaginase
PEG-L-Asparaginase (Enzon - Kyowa Hakko)
PEGLA
Polyethylene Glycol L-Asparaginase
Polyethylene Glycol-L-Asparaginase
(11beta)-11,17,21-Trihydroxypregna-1,4-diene-3,20-dione
.delta.1-Hydrocortisone
Adnisolone
Aprednislon
Capsoid
Cortalone
Cortisolone
Dacortin H
Decaprednil
Decortin H
Delta(1)Hydrocortisone
Delta- Cortef
Delta-Cortef
Delta-Diona
Delta-F
Delta-Phoricol
Delta1-dehydro-hydrocortisone
Deltacortril
Deltahydrocortisone
Deltasolone
Deltidrosol
Dhasolone
Di-Adreson-F
Dontisolon D
Estilsona
Fisopred
Frisolona
Gupisone
Hostacortin H
Hydeltra
Hydeltrasol
Klismacort
Kuhlprednon
Lenisolone
Lepi-Cortinolo
Linola-H N
Linola-H-Fett N
Longiprednil
Metacortandralone
Meti Derm
Meticortelone
Opredsone
Panafcortelone
Precortisyl
Pred-Clysma
Predeltilone
Predni-Coelin
Predni-Helvacort
Prednicortelone
Prednisolonum
Prelone
Prenilone
Sterane
.delta.1-Cortisone
1, 2-Dehydrocortisone
Adasone
Cortancyl
Dacortin
DeCortin
Decortisyl
Decorton
Delta 1-Cortisone
Delta-Dome
Deltacortene
Deltacortisone
Deltadehydrocortisone
Deltasone
Deltison
Deltra
Econosone
Lisacort
Meprosona-F
Metacortandracin
Meticorten
Ofisolona
Orasone
Panafcort
Panasol-S
Paracort
Perrigo Prednisone
PRED
Predicor
Predicorten
Prednicen-M
Prednicort
Prednidib
Prednilonga
Predniment
Prednisone Intensol
Prednisonum
Prednitone
Promifen
Rayos
Servisone
SK-Prednisone
Cancer Radiotherapy
Energy Type
ENERGY_TYPE
Irradiate
Irradiated
Irradiation
Radiation
Radiation Therapy, NOS
Radiotherapeutics
Radiotherapy
RT
Therapy, Radiation
2-Amino 6MP
2-Amino-1,7-dihydro-6H-purine-6-thione
2-Amino-6-mercaptopurine
2-Amino-6-purinethiol
2-Aminopurin-6-thiol
2-Aminopurine-6(1H)-thione
2-Aminopurine-6-thiol
2-Aminopurine-6-thiol Hemihydrate
2-Mercapto-6-aminopurine
6-Amino-2-mercaptopurine
6-Mercapto-2-aminopurine
6-Mercaptoguanine
6-TG
6H-Purine-6-thione, 2-amino-1,7-dihydro- (9CI)
BW 5071
Lanvis
Tabloid
Thioguanine Hemihydrate
Thioguanine Hydrate
Tioguanin
Tioguanine
Wellcome U3B
WR-1141
X 27
LCR
Leurocristine
VCR
Vincrystine
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Patients must be \> 365 days and \< 18 years (for AIEOP-BFM), \> 365 days and \< 22 years (for Children's Oncology Group \[COG\]) and \> 365 days and \< 46 years (for ALLTogether sites) at the time of enrollment
* Newly-diagnosed Ph+ or ABL-class Ph-like B-ALL. Leukemic blasts must express CD19. ABL-class fusions are defined as rearrangements involving the following genes predicted to be sensitive to imatinib and/or dasatinib: ABL1, ABL2, CSF1R, and PDGFRB
* Evidence of BCR::ABL1 should be documented by a clinically-validated assay prior to study entry on day 15 from the first dose of vinCRIStine during Induction therapy. ABL-class Ph-like B-ALL gene rearrangements should be documented by a clinically-validated assay and enrolled on study by day 1 of Blinatumomab Block 1. Accepted methods of detection include fluorescence in situ hybridization (FISH) using break-apart of colocalization signal probes, singleplex or multiplex reverse-transcription polymerase chain reaction (RT-PCR), whole-transcriptome or panel-based ribonucleic acid (RNA) sequencing (e.g., Hematologic Cancer Fusion Analysis, TruSight RNA Pan-Cancer Panel or equivalent). Confirmation of 5' fusion partner genes is not required for study enrollment
* Patients with Ph+ B-ALL must have previously started Induction therapy, which includes vinCRIStine, a corticosteroid, pegaspargase or calaspargase pegol, with or without anthracycline, and/or other standard cytotoxic chemotherapy
* Patients with Ph+ B-ALL have not received more than 14 days of systemic Induction therapy beginning with the first Induction dose of vinCRIStine
* Patients with ABL-class Ph-like B-ALL must have previously completed 4 or 5 weeks of multiagent Induction chemotherapy (Induction 1A)
* Patients may have started either imatinib or dasatinib prior to study entry but should have received no more than 14 days of TKI for Ph+ B-ALL or no more than 35 days of TKI for ABL-class Ph-like B-ALL
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of ≤ 2 or Karnofsky and Lansky performance scores ≥ 50%. Use Karnofsky for patients \> 16 years of age and Lansky for patients ≤ 16 years of age
* For pediatric patients (age 1-17 years): a glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m\^2, as determined by one of the following methods (must be performed within 7 days prior to enrollment unless otherwise indicated):
* Estimated GFR (eGFR) ≥ 50 mL/min/1.73 m2
* Measured GFR ≥ 50 mL/min/1.73 m\^2 (any age). If measured GFR is used, it must be performed using direct measurement with a nuclear blood sampling method or small molecule clearance method (iothalamate or other molecule per institutional standard
* For adult patients (age 18 years or older): Creatinine clearance ≥ 30 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on body weight
* Direct bilirubin \< 2.0 mg/dL (34.2 micromoles/L) (must be performed within 7 days prior to enrollment unless otherwise indicated)
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 10 x upper limit of normal (ULN) (must be performed within 7 days prior to enrollment unless otherwise indicated)
* \* Shortening fraction of ≥ 27% by echocardiogram (must be obtained within 21 days prior to enrollment and start of protocol therapy \[repeat if necessary\]) OR
* Left Ventricular Ejection fraction of ≥ 50% by radionuclide angiogram or echocardiogram (must be obtained within 21 days prior to enrollment and start of protocol therapy \[repeat if necessary\]) AND
* Corrected QT Interval, QTc \< 480mSec (must be obtained within 21 days prior to enrollment and start of protocol therapy \[repeat if necessary\])
* Note: Repeat echocardiogram and electrocardiogram are not required if they were performed at or after initial ALL diagnosis before study enrollment
* Newly-diagnosed Ph+ or ABL-class Ph-like B-ALL. Leukemic blasts must express CD19. ABL-class fusions are defined as rearrangements involving the following genes predicted to be sensitive to imatinib and/or dasatinib: ABL1, ABL2, CSF1R, and PDGFRB
* Evidence of BCR::ABL1 should be documented by a clinically-validated assay prior to study entry on day 15 from the first dose of vinCRIStine during Induction therapy. ABL-class Ph-like B-ALL gene rearrangements should be documented by a clinically-validated assay and enrolled on study by day 1 of Blinatumomab Block 1. Accepted methods of detection include fluorescence in situ hybridization (FISH) using break-apart of colocalization signal probes, singleplex or multiplex reverse-transcription polymerase chain reaction (RT-PCR), whole-transcriptome or panel-based ribonucleic acid (RNA) sequencing (e.g., Hematologic Cancer Fusion Analysis, TruSight RNA Pan-Cancer Panel or equivalent). Confirmation of 5' fusion partner genes is not required for study enrollment
* Patients with Ph+ B-ALL must have previously started Induction therapy, which includes vinCRIStine, a corticosteroid, pegaspargase or calaspargase pegol, with or without anthracycline, and/or other standard cytotoxic chemotherapy
* Patients with Ph+ B-ALL have not received more than 14 days of systemic Induction therapy beginning with the first Induction dose of vinCRIStine
* Patients with ABL-class Ph-like B-ALL must have previously completed 4 or 5 weeks of multiagent Induction chemotherapy (Induction 1A)
* Patients may have started either imatinib or dasatinib prior to study entry but should have received no more than 14 days of TKI for Ph+ B-ALL or no more than 35 days of TKI for ABL-class Ph-like B-ALL
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of ≤ 2 or Karnofsky and Lansky performance scores ≥ 50%. Use Karnofsky for patients \> 16 years of age and Lansky for patients ≤ 16 years of age
* For pediatric patients (age 1-17 years): a glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m\^2, as determined by one of the following methods (must be performed within 7 days prior to enrollment unless otherwise indicated):
* Estimated GFR (eGFR) ≥ 50 mL/min/1.73 m2
* Measured GFR ≥ 50 mL/min/1.73 m\^2 (any age). If measured GFR is used, it must be performed using direct measurement with a nuclear blood sampling method or small molecule clearance method (iothalamate or other molecule per institutional standard
* For adult patients (age 18 years or older): Creatinine clearance ≥ 30 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on body weight
* Direct bilirubin \< 2.0 mg/dL (34.2 micromoles/L) (must be performed within 7 days prior to enrollment unless otherwise indicated)
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 10 x upper limit of normal (ULN) (must be performed within 7 days prior to enrollment unless otherwise indicated)
* \* Shortening fraction of ≥ 27% by echocardiogram (must be obtained within 21 days prior to enrollment and start of protocol therapy \[repeat if necessary\]) OR
* Left Ventricular Ejection fraction of ≥ 50% by radionuclide angiogram or echocardiogram (must be obtained within 21 days prior to enrollment and start of protocol therapy \[repeat if necessary\]) AND
* Corrected QT Interval, QTc \< 480mSec (must be obtained within 21 days prior to enrollment and start of protocol therapy \[repeat if necessary\])
* Note: Repeat echocardiogram and electrocardiogram are not required if they were performed at or after initial ALL diagnosis before study enrollment
Exclusion Criteria
* Known history of chronic myeloid leukemia (CML)
* ABL-class Ph-like B-ALL who are CNS2 or CNS3 at end of Induction phase
* 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 (trisomy 21)
* 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 negative pregnancy test is required for female patients of childbearing potential within 7 days prior to enrollment
* Lactating females who plan to breastfeed their infants
* Sexually active male and female patients of reproductive potential who have not agreed to use an effective contraception method for the duration of treatment according to protocol
* NOTE: Patients who could become pregnant or could father a child must use effective contraception during protocol treatment and for 30 days after the last dose of dasatinib or 14 days after the last dose of imatinib dose or per institutional standard of care for multiagent chemotherapy, whichever is longer
* Prior treatment with TKIs before study entry with the exception of imatinib or dasatinib
* Patients with congenital long QT syndrome, history of ventricular arrhythmias, or heart block
* Patients with known Charcot-Marie-Tooth disease
* Patients with significant central nervous system pathology that would preclude treatment with blinatumomab, including history of severe neurologic disorder or autoimmune disease with central nervous system (CNS) involvement
* Note: Patients with a history of seizures that are well controlled on stable doses of anti-epileptic drugs are eligible. Patients with a history of cerebrovascular ischemia/hemorrhage with residual deficits are not eligible. Patients with a history of cerebrovascular ischemia/hemorrhage remain eligible provided all neurologic deficits have resolved
* HIV-infected patients are eligible if on effective anti-retroviral therapy that does not interact with planned study agents and with undetectable viral load within 6 months of treatment
* 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
* ABL-class Ph-like B-ALL who are CNS2 or CNS3 at end of Induction phase
* 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 (trisomy 21)
* 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 negative pregnancy test is required for female patients of childbearing potential within 7 days prior to enrollment
* Lactating females who plan to breastfeed their infants
* Sexually active male and female patients of reproductive potential who have not agreed to use an effective contraception method for the duration of treatment according to protocol
* NOTE: Patients who could become pregnant or could father a child must use effective contraception during protocol treatment and for 30 days after the last dose of dasatinib or 14 days after the last dose of imatinib dose or per institutional standard of care for multiagent chemotherapy, whichever is longer
* Prior treatment with TKIs before study entry with the exception of imatinib or dasatinib
* Patients with congenital long QT syndrome, history of ventricular arrhythmias, or heart block
* Patients with known Charcot-Marie-Tooth disease
* Patients with significant central nervous system pathology that would preclude treatment with blinatumomab, including history of severe neurologic disorder or autoimmune disease with central nervous system (CNS) involvement
* Note: Patients with a history of seizures that are well controlled on stable doses of anti-epileptic drugs are eligible. Patients with a history of cerebrovascular ischemia/hemorrhage with residual deficits are not eligible. Patients with a history of cerebrovascular ischemia/hemorrhage remain eligible provided all neurologic deficits have resolved
* HIV-infected patients are eligible if on effective anti-retroviral therapy that does not interact with planned study agents and with undetectable viral load within 6 months of treatment
* 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
Minimum Eligible Age
366 Days
Maximum Eligible Age
46 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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National Cancer Institute (NCI)
NIH
Sponsor Role
lead
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Responsibility Role
SPONSOR
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Thai Hoa Tran
Role: PRINCIPAL_INVESTIGATOR
Children's Oncology Group
Locations
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Children's Hospital of Alabama
Birmingham, Alabama, United States
Site Status
RECRUITING
Phoenix Childrens Hospital
Phoenix, Arizona, United States
Site Status
RECRUITING
Arkansas Children's Hospital
Little Rock, Arkansas, United States
Site Status
RECRUITING
Loma Linda University Medical Center
Loma Linda, California, United States
Site Status
RECRUITING
Kaiser Permanente-Oakland
Oakland, California, United States
Site Status
RECRUITING
Children's Hospital of Orange County
Orange, California, United States
Site Status
RECRUITING
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States
Site Status
RECRUITING
Children's Hospital Colorado
Aurora, Colorado, United States
Site Status
RECRUITING
Yale University
New Haven, Connecticut, United States
Site Status
RECRUITING
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States
Site Status
RECRUITING
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, United States
Site Status
RECRUITING
Children's National Medical Center
Washington D.C., District of Columbia, United States
Site Status
RECRUITING
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, United States
Site Status
RECRUITING
University of Florida Health Science Center - Gainesville
Gainesville, Florida, United States
Site Status
RECRUITING
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida, United States
Site Status
RECRUITING
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, United States
Site Status
RECRUITING
Arnold Palmer Hospital for Children
Orlando, Florida, United States
Site Status
RECRUITING
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, United States
Site Status
RECRUITING
Augusta University Medical Center
Augusta, Georgia, United States
Site Status
RECRUITING
Memorial Health University Medical Center
Savannah, Georgia, United States
Site Status
RECRUITING
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, United States
Site Status
RECRUITING
Saint Luke's Cancer Institute - Boise
Boise, Idaho, United States
Site Status
RECRUITING
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States
Site Status
RECRUITING
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Site Status
RECRUITING
Advocate Children's Hospital-Oak Lawn
Oak Lawn, Illinois, United States
Site Status
RECRUITING
Advocate Children's Hospital-Park Ridge
Park Ridge, Illinois, United States
Site Status
RECRUITING
Southern Illinois University School of Medicine
Springfield, Illinois, United States
Site Status
RECRUITING
Riley Hospital for Children
Indianapolis, Indiana, United States
Site Status
RECRUITING
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, United States
Site Status
RECRUITING
Ochsner Medical Center Jefferson
New Orleans, Louisiana, United States
Site Status
RECRUITING
Maine Children's Cancer Program
Scarborough, Maine, United States
Site Status
RECRUITING
Sinai Hospital of Baltimore
Baltimore, Maryland, United States
Site Status
RECRUITING
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
Site Status
RECRUITING
UMass Memorial Medical Center - University Campus
Worcester, Massachusetts, United States
Site Status
RECRUITING
C S Mott Children's Hospital
Ann Arbor, Michigan, United States
Site Status
RECRUITING
Children's Hospital of Michigan
Detroit, Michigan, United States
Site Status
RECRUITING
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, United States
Site Status
RECRUITING
Bronson Methodist Hospital
Kalamazoo, Michigan, United States
Site Status
RECRUITING
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, United States
Site Status
RECRUITING
University of Mississippi Medical Center
Jackson, Mississippi, United States
Site Status
RECRUITING
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, United States
Site Status
RECRUITING
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, United States
Site Status
RECRUITING
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas, Nevada, United States
Site Status
RECRUITING
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, United States
Site Status
RECRUITING
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, United States
Site Status
RECRUITING
Saint Joseph's Regional Medical Center
Paterson, New Jersey, United States
Site Status
RECRUITING
Albany Medical Center
Albany, New York, United States
Site Status
RECRUITING
Roswell Park Cancer Institute
Buffalo, New York, United States
Site Status
RECRUITING
NYU Langone Hospital - Long Island
Mineola, New York, United States
Site Status
RECRUITING
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, United States
Site Status
RECRUITING
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Site Status
RECRUITING
Stony Brook University Medical Center
Stony Brook, New York, United States
Site Status
RECRUITING
State University of New York Upstate Medical University
Syracuse, New York, United States
Site Status
RECRUITING
New York Medical College
Valhalla, New York, United States
Site Status
RECRUITING
Mission Hospital
Asheville, North Carolina, United States
Site Status
RECRUITING
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, United States
Site Status
RECRUITING
Duke University Medical Center
Durham, North Carolina, United States
Site Status
RECRUITING
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
Site Status
RECRUITING
Children's Hospital Medical Center of Akron
Akron, Ohio, United States
Site Status
RECRUITING
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Site Status
RECRUITING
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, United States
Site Status
RECRUITING
Dayton Children's Hospital
Dayton, Ohio, United States
Site Status
RECRUITING
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio, United States
Site Status
RECRUITING
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Site Status
RECRUITING
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, United States
Site Status
RECRUITING
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States
Site Status
RECRUITING
Prisma Health Richland Hospital
Columbia, South Carolina, United States
Site Status
RECRUITING
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, United States
Site Status
RECRUITING
East Tennessee Childrens Hospital
Knoxville, Tennessee, United States
Site Status
RECRUITING
The Children's Hospital at TriStar Centennial
Nashville, Tennessee, United States
Site Status
RECRUITING
Dell Children's Medical Center of Central Texas
Austin, Texas, United States
Site Status
RECRUITING
Driscoll Children's Hospital
Corpus Christi, Texas, United States
Site Status
RECRUITING
Medical City Dallas Hospital
Dallas, Texas, United States
Site Status
RECRUITING
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, United States
Site Status
RECRUITING
El Paso Children's Hospital
El Paso, Texas, United States
Site Status
RECRUITING
Cook Children's Medical Center
Fort Worth, Texas, United States
Site Status
RECRUITING
Covenant Children's Hospital
Lubbock, Texas, United States
Site Status
RECRUITING
UMC Cancer Center / UMC Health System
Lubbock, Texas, United States
Site Status
RECRUITING
Children's Hospital of San Antonio
San Antonio, Texas, United States
Site Status
RECRUITING
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States
Site Status
RECRUITING
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States
Site Status
RECRUITING
Primary Children's Hospital
Salt Lake City, Utah, United States
Site Status
RECRUITING
University of Vermont and State Agricultural College
Burlington, Vermont, United States
Site Status
RECRUITING
University of Virginia Cancer Center
Charlottesville, Virginia, United States
Site Status
RECRUITING
Inova Fairfax Hospital
Falls Church, Virginia, United States
Site Status
RECRUITING
Children's Hospital of The King's Daughters
Norfolk, Virginia, United States
Site Status
RECRUITING
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, United States
Site Status
RECRUITING
Seattle Children's Hospital
Seattle, Washington, United States
Site Status
RECRUITING
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, United States
Site Status
RECRUITING
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, United States
Site Status
RECRUITING
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin, United States
Site Status
RECRUITING
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, United States
Site Status
RECRUITING
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States
Site Status
RECRUITING
IWK Health Centre
Halifax, Nova Scotia, Canada
Site Status
RECRUITING
Hospital for Sick Children
Toronto, Ontario, Canada
Site Status
RECRUITING
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, Canada
Site Status
RECRUITING
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, Canada
Site Status
RECRUITING
Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
Sherbrooke, Quebec, Canada
Site Status
RECRUITING
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
Québec, , Canada
Site Status
RECRUITING
University Pediatric Hospital
San Juan, , Puerto Rico
Site Status
RECRUITING
Countries
Review the countries where the study has at least one active or historical site.
United States
Canada
Puerto Rico
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
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Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
NCI-2023-09214
Identifier Type: REGISTRY
Identifier Source: secondary_id
AALL2131
Identifier Type: OTHER
Identifier Source: secondary_id
AALL2131
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2023-09214
Identifier Type: -
Identifier Source: org_study_id