Blinatumomab and Nivolumab With or Without Ipilimumab in Treating Patients With Poor-Risk Relapsed or Refractory CD19+ Precursor B-Lymphoblastic Leukemia

PRIMARY OBJECTIVES: I. To evaluate the safety and tolerability of the blinatumomab given in combination with nivolumab alone, or in combination with both nivolumab and ipilimumab in subjects with poor-risk, relapsed or refractory CD19+ pre-B cell acute lymphoblastic leukemia (ALL) or CD19+ mixed phenotype acute leukemia (MPAL). II. To determine the maximum tolerated dose (MTD) of the combination of blinatumomab plus nivolumab, and blinatumomab plus both nivolumab and ipilimumab and to further confirm the safety of the combination therapy in subjects with poor-risk, relapsed or refractory CD19+ pre-B cell ALL or CD19+ mixed phenotype acute leukemia (MPAL). SECONDARY OBJECTIVES: I. To observe and record anti-leukemia activity of blinatumomab and nivolumab, and blinatumomab plus both nivolumab and ipilimumab, including the effects on minimal residual disease (MRD). II. To assess preliminary anti-leukemia activity in expansion cohorts of patients with poor-risk, relapsed or refractory CD19+ precursor B-lymphoblastic leukemia, or CD19+ mixed phenotype acute leukemia (MPAL). EXPLORATORY OBJECTIVES: I. To examine changes in absolute lymphocyte count and distribution of T cell subsets (CD4+, CD8+, regulatory T cells \[Tregs\], effector T cells \[Teffs\]) and their differentiation status, natural killer (NK) cells, and B cells before and post-blinatumomab, and immune checkpoint inhibitor(s) therapy in both peripheral blood and the bone marrow microenvironment. II. To explore changes in T cell co-signaling receptors expression in defined T cell subpopulations and their canonic transcription factor expression in both peripheral blood and bone marrow before and post-blinatumomab, and immune checkpoint inhibitor(s) therapy. III. To examine changes in expression of co-signaling molecules on leukemia blasts (CD10+/CD19+/CD34+) before and after treatment with blinatumomab and checkpoint inhibitors. IV. To examine the serum levels of cytokines before and after treatment with blinatumomab and checkpoint inhibitors, including the levels of sCTLA-4. V. To perform immune profiling of T cell repertoire and characterize T cell transcriptional signature before and after treatment. OUTLINE: This is a safety and tolerability study of blinatumomab given in combination with nivolumab alone, or in combination with both nivolumab and ipilimumab. Patients receive blinatumomab intravenously (IV) continuously on days 1-28. Treatment repeats every 42 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive nivolumab IV over 30 minutes on day 11 and then every 2 weeks for up to year. Some patients also receive ipilimumab IV over 90 minutes on day 11 and then every 6 weeks for up to 1 year. Patients also undergo bone marrow aspiration and biopsy and blood sample collection throughout the study. After completion of study treatment, patients are followed up every 3 months for up to 2 years.