Rituximab and Combination Chemotherapy in Treating Patients With Newly Diagnosed Primary CNS Lymphoma

OBJECTIVES: Primary * Determine the complete response rate after remission induction therapy with the combination of high-dose methotrexate (HDMTX), temozolomide, and rituximab at 4 months. Secondary * Determine the safety and feasibility of consolidation therapy comprising cytarabine and etoposide administered after induction therapy in these patients. * Determine the percentage of patients who achieve durable (complete and partial) remission when treated with this regimen. * Determine relapse-free survival after complete response in patients treated with this regimen. * Correlate molecular markers with outcome in patients treated with this regimen. * Determine the effects of this regimen on neurological function in these patients. OUTLINE: This is a multicenter study. * Induction Chemotherapy: All induction therapy courses repeat every 28 days. * Courses 1-3: Patients receive high-dose methotrexate IV over 4 hours on days 1 and 15, leucovorin calcium IV or orally every 6 hours beginning on days 2 and 16 and continuing until blood levels of methotrexate are in a safe range, and oral temozolomide on days 7-11. Patients also receive rituximab\* IV on days 3, 10, 17, and 24 of course 1 and days 3 and 10 of course 2 (total of 6 doses). NOTE: \*Patients diagnosed with T-cell primary CNS lymphoma do not receive rituximab. * Course 4: Patients receive oral temozolomide on days 7-11, high-dose methotrexate IV over 4 hours on day 15, and leucovorin calcium IV or orally every 6 hours beginning on day 16 and continuing until blood levels of methotrexate are in a safe range. Patients achieving a complete response or a complete response unconfirmed proceed to consolidation therapy. * Consolidation therapy I (course 5): Beginning 4 weeks after the start of course 4, patients receive high-dose methotrexate IV over 4 hours on day 1, leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until blood levels of methotrexate are in a safe range, and oral temozolomide on days 7-11. * Consolidation therapy II (course 6): Beginning 3-5 weeks after the start of course 5, patients receive cytarabine IV over 2 hours twice daily and etoposide IV over 12 hours twice daily on days 1-4 and filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously beginning on day 14 and continuing until blood counts recover. Treatment continues in the absence of disease progression. After completion of study treatment, patients are followed periodically for 3 years. PROJECTED ACCRUAL: A total of 27-45 patients will be accrued for this study within 2-3 years.