• Progression-free survival [ Designated as safety issue: No ]
• Proportion progression free [ Designated as safety issue: No ]
• Survival [ Designated as safety issue: No ]

• Progression-free survival
• Proportion progression free
• Survival

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as methotrexate, leucovorin, vincristine, procarbazine, dexamethasone, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy works in treating patients with primary central nervous system (CNS) lymphoma.

OBJECTIVES:

Primary

• Determine the complete response rate.

Secondary

• Determine the progression-free survival of these patients.
• Determine the proportion of progression-free and overall survival in these patients.
• Determine rituximab cerebrospinal fluid pharmacokinetics (only in patients requiring intrathecal chemotherapy).

OUTLINE: This is a multicenter study.

Patients receive rituximab IV 3 times weekly in weeks 1-4; high-dose methotrexate IV over 2 hours in weeks 1, 3, 5, and 9; oral or IV leucovorin calcium every 6 hours for 12 doses beginning 24 hours after the start of methotrexate in weeks 1, 3, 5, and 9; vincristine IV in weeks 1, 3, 5, 7, and 9; oral procarbazine hydrochloride daily on days 1-7 in weeks 1, 5, and 9; oral dexamethasone daily in weeks 1-6; and cytarabine IV over 2 hours twice weekly in weeks 11 and 14.

Patients with positive cerebrospinal fluid also receive methotrexate intrathecally and oral leucovorin calcium every 12 hours for 8 doses beginning 24 hours after the start of methotrexate in weeks 2, 4, 6, 8, and 10.

After completion of study treatment, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.

• Biological: rituximab
• Drug: cytarabine
• Drug: dexamethasone
• Drug: leucovorin calcium
• Drug: methotrexate
• Drug: procarbazine hydrochloride
• Drug: vincristine sulfate

DISEASE CHARACTERISTICS:

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

• Patients with inconclusive biopsy or patients who are not candidates for biopsy must have typical CT scan or MRI of the brain AND meet ≥ 1 of the following criteria:

  • Positive cerebrospinal fluid cytology for lymphoma OR a monoclonal lymphoid population as defined by cell surface markers or immunoglobulin gene rearrangement studies
  • Biopsy-proven involvement of the vitreous or uvea if cells are apparent in the posterior chamber or vitreous by ophthalmological examination

• Bideminsionally measurable disease, defined as contrast-enhancing tumor ≥ 1 cm by pretreatment MRI/CT scan

  • Meningeal or vitreous involvement constitutes evaluable but not measurable disease
  • If an excisional, rather than a needle biopsy was done, measurable disease must be present on a postoperative scan
  • PET-CT scan not allowed
• No systemic lymphoma (as determined by pre-registration CT scans and physical examination)

PATIENT CHARACTERISTICS:

• ECOG performance status 0-3
• Absolute granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ upper limit of normal (ULN)
• SGOT ≤ 2.0 times ULN
• Creatinine clearance ≥ 50 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No HIV-1 positivity
• No other malignancy within the past 5 years except basal cell skin cancer or any carcinoma in situ
• No pre-existing immunodeficiency
• No hepatitis B surface antigen positivity

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy or radiotherapy for primary central nervous system lymphoma
• No prior organ or bone marrow transplantation