Blinatumomab, Methotrexate, Cytarabine, and Ponatinib in Treating Patients With Philadelphia Chromosome-Positive, or BCR-ABL Positive, or Relapsed/Refractory, Acute Lymphoblastic Leukemia

PRIMARY OBJECTIVES: I. To evaluate the complete molecular response rate in cohort 1 (newly diagnosed Philadelphia chromosome \[Ph-positive\] and/or BCR-ABL-positive acute lymphoblastic leukemia \[ALL\]) and the overall response (complete remission \[CR\]+CR with incomplete blood count recovery \[CRi\]) rate in cohort 2 (relapsed/refractory disease). SECONDARY OBJECTIVES: I. To evaluate other clinical efficacy endpoints (complete cytogenetic response, complete molecular response \[CMR\], event-free survival \[EFS\] and overall survival \[OS\]) and safety of the regimen. EXPLORATORY OBJECTIVES: I. To characterize the role of ABL1 kinase domain mutations on treatment failure and relapse in patients with Ph+ ALL treated with blinatumomab ponatinib. II. To determine the impact of recurrent genomic alterations at diagnosis on relapse-free survival (RFS) in patients with Ph+ ALL treated with blinatumomab plus ponatinib. III. To investigate the impact of next-generation sequencing-based minimal residual disease assessment on relapse-free survival in patients with Ph+ ALL. IV. To determine the effect on immune cell subsets in patients with Ph+ ALL treated with blinatumomab plus ponatinib. OUTLINE: Patients receive blinatumomab intravenously (IV) nonstop on days 1-28 of cycles 1-5, and methotrexate and cytarabine intrathecally (by spinal tap) on days 1, 15, and 29 of cycles 1-4. Patients also receive ponatinib orally (PO) daily. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and every 6 months thereafter.