Testing the Addition of Lenalidomide and Nivolumab to the Usual Treatment for Primary CNS Lymphoma

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PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose (MTD) of lenalidomide when given in combination with high dose-methotrexate (HD-MTX) and rituximab, with or without nivolumab, as induction treatment of primary CNS lymphoma. II. Determine the proportion of patients who are able to stay on ...

PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose (MTD) of lenalidomide when given in combination with high dose-methotrexate (HD-MTX) and rituximab, with or without nivolumab, as induction treatment of primary CNS lymphoma. II. Determine the proportion of patients who are able to stay on maintenance therapy with lenalidomide and/or nivolumab for 6 months after induction treatment of primary CNS lymphoma. SECONDARY OBJECTIVES: I. To evaluate the overall response rate (ORR) of the combination of methotrexate, rituximab, lenalidomide, nivolumab. II. To evaluate the effect of the treatment regimen and lenalidomide / nivolumab maintenance on progression free survival (PFS). III. To evaluate the effect of the treatment regimen and lenalidomide / nivolumab maintenance on overall survival (OS). EXPLORATORY OBJECTIVES: I. To analyze tumor tissue and cerebrospinal fluid (CSF) for gene expression profiles, and to correlate these profiles with treatment outcomes. II. To determine whether CSF proteome and metabolome are predictors of outcomes (prognostic marker). III. To assess response to therapy and minimal residual disease via MRI-based metrics and minimal residual disease of blood and CSF. IV. To evaluate the relationship between neurocognitive deficits and tumor and brain volumetrics, as assessed by magnetic resonance imaging (MRI) and tumor metabolism. OUTLINE: This is a dose-escalation study of lenalidomide. INDUCTION: Patients receive rituximab intravenously (IV) on day 1, methotrexate IV over 2 hours or orally (PO) on day 2, lenalidomide PO daily on days 5-14, and nivolumab IV over 30 minutes on day 14. (In dose level IV that includes nivolumab, the doses of rituximab for cycles 2-6 may be given on the same day as nivolumab for the previous cycle). Treatment repeats every 14 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response, partial response, or stable disease proceed to maintenance therapy. MAINTENANCE: Within 5 weeks after the last dose of lenalidomide in induction therapy, patients receive lenalidomide PO daily on days 1-21, and nivolumab IV over 30 minutes on day 1. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for up to 3 years.

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