Nivolumab and Combination Chemotherapy in Treating Participants With Diffuse Large B-Cell Lymphoma

PRIMARY OBJECTIVES: I. To identify the maximum tolerated dose (MTD) for the combination treatment of nivolumab and rituximab, cyclophosphamide, doxorubicin hydrochloride (doxorubicin), vincristine sulfate (vincristine), and prednisone (R-CHOP) in patients with diffuse large B-cell lymphoma (DLBCL). (Phase I) II. To assess the impact of nivolumab + R-CHOP on response by looking at complete response (CR) rates. (Phase II) SECONDARY OBJECTIVES: I. To look at preliminary efficacy as measured by overall response rate for combination nivolumab + R-CHOP. II. To assess the impact of nivolumab + R-CHOP on survival outcomes, specifically progression-free survival (PFS), overall survival (OS) and event-free-survival (EFS). III. To assess toxicity and tolerability of patients treated with nivolumab + R-CHOP. IV. To assess quality of life in patients treated with nivolumab + R-CHOP. EXPLORATORY OBJECTIVES: I. To explore the impact of the PD-1:PD-L1 regulatory axis and targeting this axis on the immune microenvironment. II. To identify the process of cachexia as a potential mechanism of resistance to anti-PD-1 therapy. OUTLINE: This is a phase I, dose-escalation study of nivolumab followed by a phase II study. Participants receive nivolumab intravenously (IV) over 30 minutes on day 1. Participants also receive rituximab IV on day 2, cyclophosphamide IV on day 2, doxorubicin hydrochloride IV over 3-5 hours on day 2, vincristine sulfate IV over 30 minutes on day 2, and prednisone orally (PO) on days 2-6 of course 1 and rituximab IV on day 1, cyclophosphamide IV on day 1, doxorubicin hydrochloride IV over 3-5 hours on day 1, vincristine sulfate IV over 30 minutes on day 1, and prednisone PO on days 1-5 of courses 2-6. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed for up to 18 months.