Blinatumomab and Combination Chemotherapy or Dasatinib, Prednisone, and Blinatumomab in Treating Older Patients With Acute Lymphoblastic Leukemia

PRIMARY OBJECTIVES: I. To evaluate the 3-year survival rate in elderly patients with newly diagnosed Philadelphia (Ph)-negative acute lymphoblastic leukemia (ALL) treated with blinatumomab followed by POMP (prednisone, vincristine sulfate, methotrexate, and mercaptopurine) maintenance. II. To evaluate in a preliminary manner (feasibility study) the safety of dasatinib-steroid based induction followed by blinatumomab treatment in combination with dasatinib followed by dasatinib-based maintenance in patients with newly diagnosed Ph-positive ALL, relapsed/refractory Ph-positive ALL, and Ph-like dasatinib-sensitive mutations or kinase fusions (DSMKF) ALL (newly-diagnosed relapsed or refractory). SECONDARY OBJECTIVES: I. To evaluate toxicities in these patient populations treated with these regimens. II. To estimate the rates of complete response (CR), complete remission with incomplete count recovery (CRi) and disease-free survival in Ph-negative patients. III. To estimate disease-free and overall survival in Ph-positive ALL and Ph-like DSMKF ALL. IV. To estimate in each cohort the rate of minimal residual disease (MRD) negativity, and the time to achieve MRD negativity (exploratory analysis). V. To determine whether anti-idiotype antibodies directed against blinatumomab develop with blinatumomab treatment in this study. ADDITIONAL TRANSLATIONAL MEDICINE OBJECTIVES: I. To estimate the incidence of the Ph-like signature in elderly patients (\>= 65 years of age) with newly diagnosed Philadelphia-chromosome negative ALL. II. To estimate the incidence of the various tyrosine-kinase fusions, making up the Ph-like signature in elderly patients with newly diagnosed Philadelphia-chromosome negative ALL. III. To evaluate outcomes (event free survival \[EFS\] and overall survival \[OS\]) in patients with the Ph-like signature versus those without the Ph-like signature in Ph-negative ALL. IV. To describe via single cell transcriptomics the clonal diversity in gene expression of participants on the trial. V. To describe the methylation status of the overall genome as well as key driver genes of all participants in the trial. OUTLINE: Patients are assigned to 1 of 2 treatment cohorts according to Philadelphia chromosome status. COHORT I (PHILADELPHIA CHROMOSOME NEGATIVE PATIENTS): INDUCTION: Patients receive blinatumomab intravenously (IV) continuously over 24 hours on days 1-28 in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray and echocardiography (ECHO) during screening and a computed tomography (CT) scan and/or magnetic resonance imaging (MRI) as well as blood sample collection and bone marrow aspiration and biopsy throughout the trial. Patients undergo a lumbar puncture during screening and on study. Patients may also undergo a biopsy during screening. (Closed to accrual 06/29/17) RE-INDUCTION: Patients not achieving CR or CRi after Induction, receive blinatumomab IV continuously over 24 hours on days 1-28 in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray and ECHO during screening and a CT scan and/or MRI as well as blood sample collection and bone marrow aspiration and biopsy throughout the trial. Patients undergo a lumbar puncture during screening and on study. Patients may also undergo a biopsy during screening. POST-REMISSION: Patients receive blinatumomab IV continuously over 24 hours on days 1-28. Treatment repeats every 42 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and/or MRI on study and during follow-up. Patients also undergo blood sample collection, lumbar puncture, and bone marrow aspiration and biopsy on study. MAINTENANCE: Patients receive prednisone orally (PO) on days 1-5, vincristine sulfate IV on day 1, mercaptopurine PO on days 1-28, and methotrexate PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 18 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and/or MRI on study and during follow-up. Patients also undergo a lumbar puncture and bone marrow aspiration and biopsy on study. COHORT II (PHILADELPHIA CHROMOSOME POSITIVE PATIENTS): INDUCTION: Patients receive dasatinib PO on days 1-84 and prednisone PO on days 1-24 with tapering on days 25-32 in the absence of disease progression or unacceptable toxicity. Patients undergo an x-ray and ECHO during screening and a CT scan and/or MRI throughout the trial. Patients undergo a lumbar puncture and bone marrow aspiration and biopsy during screening and on study. Patients may also undergo a biopsy during screening. RE-INDUCTION: Patients receive blinatumomab IV continuously over 24 hours on days 1-28. Treatment repeats every 42 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and/or MRI on study and during follow-up. Patients also undergo blood sample collection, a lumbar puncture, and bone marrow aspiration and biopsy on study. POST-REMISSION: Patients receive blinatumomab IV continuously over 24 hours on days 1-28 and dasatinib PO on days 1-42. Treatment repeats every 42 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and/or MRI on study and during follow-up. Patients also undergo blood sample collection, lumbar puncture, and bone marrow aspiration and biopsy on study. MAINTENANCE: Patients receive dasatinib PO on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive prednisone PO on days 1-5. Treatment repeats every 28 days for 18 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and/or MRI as well as a lumbar puncture and bone marrow aspiration and biopsy on study. After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 2 years, and then annually until 10 years from initial registration.