Testing New Combination Treatments for Children and Young Adults With Philadelphia Chromosome–Positive or Ph-Like B-Cell ALL

Summary

This international pilot study is designed to evaluate chemotherapy and tyrosine kinase inhibitors in combination with blinatumomab in patients with newly diagnosed Philadelphia chromosome–positive or ABL-class Philadelphia chromosome–like B-cell acute lymphoblastic leukemia.

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 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.

To be included in AALL2131, participants must be/ have

• Must be enrolled on APEC14B1 and consented to Eligibility Screening (Part A) prior to treatment and enrollment on AALL2321.
• Age: >365 days and < 22 years at the time of enrollment.
• Diagnosis:
  • 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
• Adequate renal, liver, and cardiac function function.

To be included in AALL2131, participants must not be / have

• Known history of chronic myeloid leukemia (CML)
• Down syndrome (trisomy 21)
• 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

Keywords
Leukemia