Study on chemotherapy and experimental drugs in patients with Philadelphia Chromosome positive and ABL-class Philadelphia Chromosome-Like B-cell Acute Lymphoblastic Leukemia

Trial details

Who runs it

Universita Degli Studi Di Milano Bicocca

Trial code

EU 2025-520982-39-00

Record updated

2026. május 8.

Original description

1. To estimate the 3-year event free survival (EFS) of children, adolescents, and young adults 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. 2. To estimate the 3-year EFS of children, adolescents, and young adults 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 3. 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 TKI.Read full original descriptionShow less

AALL2131/EsPhALL2022, An International Pilot Study of Chemotherapy and Tyrosine Kinase Inhibitor with Blinatumomab in Patients with Newly Diagnosed Philadelphia Chromosome Positive or ABL-class Philadelphia Chromosome-Like B-cell Acute Lymphoblastic Leukemia

1. To estimate the 3-year event free survival (EFS) of children, adolescents, and young adults 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. 2. To estimate the 3-year EFS of children, adolescents, and young adults 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 3. 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 TKI.

Inclusion: Patients must be >365 days and <18 years (for AIEOP-BFM), >365 days and <22 years (for COG) and >365 days and <46 years (for ALLTogether sites) at the time of enrollment; Adequate liver function; Adequate cardiac function; 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; 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; 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 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; Adequate renal function.

Exclusion: Patients with significant central nervous system pathology that would preclude treatment with blinatumomab, including history of severe neurologic disorder or autoimmune disease with CNS involvement; Known history of chronic myeloid leukemia (CML); 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 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; 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; ABL-class Ph-like B-ALL who are CNS2 or CNS3 at end of Induction phase.

EU CTIS 2025-520982-39-00