Nivolumab and Ibrutinib in Treating Patients With Relapsed or Refractory Central Nervous System Lymphoma

PRIMARY OBJECTIVES: I. Determine the overall response rate of nivolumab and ibrutinib in central nervous system (CNS) lymphoma. SECONDARY OBJECTIVES: I. Determine the overall response rate of 4 weeks of ibrutinib single agent in CNS lymphoma. II. Determine the complete response rate of nivolumab and ibrutinib in CNS lymphoma. III. Determine the 1-year progression free and overall survival outcomes in CNS lymphoma. IV. Safety and toxicity of nivolumab and ibrutinib. EXPLORATORY OBJECTIVES: I. Assess activation of T cells in peripheral blood and cerebrospinal fluid. II. Assess the cytokine profile from microglial cells in cerebrospinal fluid. III. Correlate features of peripheral blood T cell activation with toxicities. IV. Correlate features of peripheral blood T cell activation with response and progression free survival (PFS). V. Correlate baseline tumor characteristics with response and PFS. VI. Evaluate the ability of minimal residual disease testing to monitor response and differentiate from pseudo progression. OUTLINE: Patients are assigned to 1 of 2 cohorts. COHORT A: Patients receive ibrutinib orally (PO) daily on days 1-28. Beginning course 1, patients also receive nivolumab intravenously (IV) over 1 hour on days 1 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. COHORT B: Patients receive ibrutinib PO daily on days 1-28 and nivolumab IV over 1 hour on days 1 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve at least a partial response after 6 courses may continue therapy for up to 2 years. After completion of study treatment, patients are followed up within 3-4 weeks and then every 3 months for 2 years.