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

Prior treatment

• 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

Other illness

• 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

Lab values

• 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

Other

• ABL-class Ph-like B-ALL who are CNS2 or CNS3 at end of Induction phase.

• 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