• Treatment related toxicity assessed by NCI CTC [ Designated as safety issue: Yes ]
• Disease-free survival at 1 year [ Designated as safety issue: No ]

• Treatment related toxicity assessed by NCI CTC
• Disease-free survival at 1 year

• Response rate assessed radiographically every 2 months [ Designated as safety issue: No ]
• Overall survival [ Designated as safety issue: No ]
• Progression-free survival [ Designated as safety issue: No ]

• Response rate assessed radiographically every 2 months
• Overall survival
• Progression-free survival

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Drugs used in immunotherapy such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells, and may make cancer cells more sensitive to chemotherapy. Radiation therapy uses high-energy x-rays to damage cancer cells. Giving lower doses of radiation may cause less damage to normal tissue.

PURPOSE: Phase II trial to study the effectiveness of combining immunotherapy with combination chemotherapy followed by low-dose radiation therapy and cytarabine in treating patients who have newly diagnosed primary central nervous system lymphoma.

OBJECTIVES:

• Determine the efficacy of induction immunochemotherapy comprising rituximab, methotrexate, procarbazine, and vincristine followed by reduced-dose radiotherapy and consolidation cytarabine in patients with newly diagnosed primary central nervous system lymphoma.
• Determine the 2-year and overall disease-free survival of patients treated with this regimen.
• Determine the progression-free and overall survival of patients treated with this regimen.
• Determine the acute treatment-related toxicity and safety of this regimen in these patients.
• Determine the initial response rate of patients treated with immunochemotherapy.
• Determine the relapse rate after complete response in patients treated with this regimen.
• Determine the neuro-cognitive outcome in patients treated with this regimen.

OUTLINE: This is a multicenter, pilot study.

• Induction immunochemotherapy: Patients receive rituximab IV over 5 hours on day 1 and methotrexate IV over 2 hours and vincristine IV over several minutes on day 2. Patients also receive oral procarbazine on days 2-8 during courses 1, 3, and 5. Treatment repeats every 2 weeks for 5 courses in the absence of disease progression or unacceptable toxicity. Patients with a partial response after 5 courses may receive an additional 2 courses.
• Radiotherapy: Beginning 3-5 weeks after completion of induction immunochemotherapy, patients undergo radiotherapy daily 5 days a week for 3-6 weeks.
• Consolidation chemotherapy: Patients receive cytarabine IV over 3 hours on days 1 and 2. Treatment repeats every 28 days for a total of 2 courses.

Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 3 years.

• Biological: rituximab
• Drug: cytarabine
• Drug: methotrexate
• Drug: procarbazine hydrochloride
• Drug: vincristine sulfate
• Radiation: radiation therapy

DISEASE CHARACTERISTICS:

• Histologically confirmed primary non-Hodgkin's lymphoma by brain biopsy

  • Patients who have an inconclusive biopsy or who are not a candidate for biopsy are eligible provided they have a typical cranial MRI or CT scan* AND meet at least 1 of the following criteria:

    • Positive cerebrospinal fluid cytology for lymphoma or a monoclonal lymphocyte population as defined by cell surface markers
    • Biopsy of the vitreous or uvea demonstrating non-Hodgkin's lymphoma NOTE: *Typical MRI or CT scan is defined as the presence of hypo-, iso-, or hyperdense parenchymal contrast-enhancing (usually homogeneously) mass lesion(s)
• HIV-1 negative

• Normal or negative pretreatment systemic evaluation including the following examinations:

  • Bone marrow aspirate and biopsy
  • CT scans of the chest, abdomen, and pelvis

PATIENT CHARACTERISTICS:

Age

• Any age

Performance status

• Not specified

Life expectancy

• At least 8 weeks

Hematopoietic

• WBC at least 4,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 2.0 mg/dL
• SGOT no greater than 2 times upper limit of normal

Renal

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance at least 50 mL/min

Other

• Not pregnant
• Fertile patients must use effective contraception during and for 6 months after study participation
• No other active primary malignancy except basal cell skin cancer or carcinoma in situ of the cervix
• No pre-existing immunodeficiency (e.g., renal transplantation recipient)
• Must maintain a tyramine-free diet (i.e., free of alcohol and certain cheeses) during procarbazine administration

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for CNS lymphoma

Endocrine therapy

• Not specified

Radiotherapy

• No prior cranial radiotherapy

Surgery

• Not specified

Other

• No citrus fruit, citrus fruit juices, or ascorbic acid supplements during and for 72 hours after methotrexate administration