This phase I/II trial studies the side effects of methotrexate, mannitol, rituximab, and carboplatin and to see how well they work in treating patients with primary central nervous system lymphoma. Drugs used in chemotherapy, such as methotrexate and carboplatin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Osmotic blood-brain barrier disruption uses mannitol to open the blood vessels around the brain and allow cancer-killing substances to be carried directly to the brain. Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Giving methotrexate, mannitol, rituximab, and carboplatin together may be an effective treatment for primary central nervous system lymphoma.

PRIMARY OBJECTIVES:

I. To evaluate the safety and toxicities of a treatment regimen consisting of rituximab (intravenously [IV]) the day prior to methotrexate (intra-arterially [IA]), and carboplatin (IA) in conjunction with blood-brain barrier disruption (BBBD) and delayed sodium thiosulfate (IV).

II. To demonstrate, adding a monoclonal antibody and carboplatin to methotrexate BBBD, that a 45% rate of complete response (CR) within the first 3 months of treatment is achieved, while excluding a CR rate as low as 30%.

SECONDARY OBJECTIVE:

I. To estimate the response rate (counting all CRs), the two-year overall survival and the two-year event-free survival, as baselines for subsequent trials.

OUTLINE:

Patients receive rituximab IV over 5 hours on day 1, mannitol IA, methotrexate IA over 10 minutes, and carboplatin IA over 10 minutes on days 2 and 3. Patients then receive sodium thiosulfate IV over 15 minutes at 4 and 8 hours after carboplatin. Treatment repeats monthly for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 2 months, then every 2 months for 2 years, every 6 months for 1 year, and then annually for at least 2 years.

Inclusion Criteria:

• Subjects with histopathologic confirmation of intermediate or high-grade primary central nervous system lymphoma (PCNSL) as documented by brain biopsy, or cytology (analysis from cerebral spinal fluid [CSF] or vitrectomy), and cluster of differentiation 20 (CD20) positive; whenever possible, the tumor should be characterized by immunophenotype
• Subjects must be =< 90 days from diagnosis of PCNSL in the brain or spine; time from pathologic diagnosis to initiation of treatment should be specified; subjects with history of only ocular lymphoma are eligible if < 90 days since documented brain parenchymal disease (by imaging or by biopsy)
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance score =< 3 (Karnofsky >= 30)
• Hematocrit >= 25% (may be reached by transfusion) (performed within 14 days of registration)
• White blood cell count >= 2.5 x 10^3/mm^3 (performed within 14 days of registration)
• Absolute granulocyte count >= 1.2 x 10^3/mm^3 (performed within 14 days of registration)
• Platelets >= 100 x 10^3/mm^3 (or >= lower limit of institutional normal value) (performed within 14 days of registration)
• Calculated creatinine clearance (Cr Cl) >= 50 ml/min (performed within 14 days of registration); eligible for full dose methotrexate
• Calculated Cr Cl >= 30 ml/min (performed within 14 days of registration); eligible for reduced dose methotrexate
• Bilirubin =< 2.0 x upper limit of institutional normal value (performed within 14 days of registration)
• The subject may have had other systemic chemotherapy for PCNSL during the 90 days since PCNSL diagnosis; prior systemic chemotherapy must have been given at least 4 weeks prior to study entry (6 weeks for nitrosourea agents), with the exceptions of methotrexate and rituximab which may have been given at least 10 days prior; ocular lymphoma treatment may have been given any time prior to study entry; if the subject has undergone treatment for parenchymal disease and the parenchymal disease has progressed on a stable or increasing dose of steroids, the subject is not eligible for enrollment
• Sexually active women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study treatment and for the duration of study treatment; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Subjects with a bone marrow biopsy which shows microscopic, low-level involvement of lymphoma are eligible
• Subject with seropositivity for hepatitis B or hepatitis C must be cleared by hepatology service prior to participating in treatment protocol

Exclusion Criteria:

• Prior cranial or spinal radiotherapy
• Subjects with radiographic signs of excessive intra-cranial mass effect with associated rapid neurologic deterioration, and/or spinal block, are unsafe to undergo BBBD chemotherapy and are not eligible
• Uncontrolled (over the last 30 days), clinically significant confounding medical conditions
• Seropositivity for the human immunodeficiency virus
• Systemic lymphoma
• Subjects who have a positive serum human chorionic gonadotropin (hCG), are pregnant or lactating are ineligible
• Known allergy to any of the study agents
• Subjects who are at significant risk for general anesthesia