Avelumab, Utomilumab, Rituximab, Ibrutinib, and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma or Mantle Cell Lymphoma

This phase I trial studies the side effects and best dose of avelumab, utomilumab, rituximab, ibrutinib, and combination chemotherapy in treating patients with diffuse large B-cell lymphoma or mantle cell lymphoma that has come back or does not respond to treatment. Monoclonal antibodies, such as avelumab, utomilumab, and rituximab, may interfere with the ability of tumor cells to grow and spread. Ibrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as etoposide phosphate, carboplatin, and ifosfamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving avelumab, utomilumab, rituximab, ibrutinib, and combination chemotherapy may work better in treating patients with diffuse large B-cell lymphoma or mantle cell lymphoma.

PRIMARY OBJECTIVES: I. Evaluate the safety and tolerability of the combination of avelumab (Ave) plus utomilumab (Uto) plus rituximab, ifosfamide, carboplatin, and etoposide phosphate (RICE) in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) as first (1st) line salvage therapy. II. Evaluate the safety and tolerability of Ave plus Uto plus rituximab (R)/ibrutinib in patients with relapsed/refractory mantle cell lymphoma (MCL). III. Determine the maximum tolerated dose (MTD) of the combination of Ave plus Uto with RICE for DLBCL. IV. Determine the MTD of the combination of Ave plus Uto with R/ibrutinib for MCL. SECONDARY OBJECTIVES: I. Estimate overall response rate (ORR), complete response (CR) rate, duration of response (DOR), and progression-free survival (PFS) of the combination therapy. II. Evaluate the stem cell mobilization rate after Ave+Uto+RICE therapy in DLBCL patients. EXPLORATORY OBJECTIVES I. Explore immunologic and genomic biomarkers of response to Ave+Uto-based combination therapy. II. Explore the use of CCND1 messenger (m)ribonucleic acid (RNA) for minimal residual disease (MRD) monitoring for MCL. OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 cohorts. COHORT I: Patients receive rituximab intravenously (IV) on day 1, etoposide phosphate IV on days 1-3, avelumab IV over 60 minutes on day 2, ifosfamide IV over 24 hours on day 2, and carboplatin IV on day 2 or rituximab IV on day 1, etoposide phosphate IV on days 1-3, avelumab IV over 60 minutes on days 2, utomilumab IV over 60 minutes on day 2, ifosfamide IV over 24 hours on day 2, and carboplatin IV on day 2. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients may then undergo autologous hematopoietic stem cell transplantation. COHORT II: Patients receive rituximab IV on day 1, avelumab IV over 60 minutes on days 2 and 16, and ibrutinib orally (PO) once daily (QD) or rituximab IV on day 1, avelumab IV over 60 minutes on days 2 and 16, utomilumab IV on day 2, and ibrutinib PO QD. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. (Closed as of 12/12/2019) After completion of study treatment, patients in cohort I are followed up for up to 3 months or 2 years and patients in cohort II are followed up at 30 and 90 days and then every 6 months for up to 2 years.