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.

DISEASE CHARACTERISTICS:

• Histologically confirmed newly diagnosed primary CNS lymphoma confirmed by 1 of the following methods:

• Brain biopsy or resection
• Cerebrospinal fluid (CSF) cytology

• Positive CSF cytology with or without measurable intracranial disease
• No evidence of systemic non-Hodgkin's lymphoma

• CT scan or MRI of the chest, abdomen, and pelvis AND bilateral bone marrow biopsy or unilateral biopsy with a 2cm core biopsy specimen that is negative for extracerebral source of lymphoma
• Measurable contrast-enhancing disease by MRI of the brain and spine (plus gadolinium) unless CSF cytology positive
• No evidence of pleural effusions or ascites

PATIENT CHARACTERISTICS:

Age

• Any age

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3

Hepatic

• ALT and AST ≤ 2 times upper limit of normal
• Bilirubin ≤ 2 mg/dL

Renal

• Creatinine clearance ≥ 50 mL/min

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 6 months after study participation
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Concurrent steroids for the management of symptoms related to lymphoma allowed

Radiotherapy

• No concurrent palliative radiotherapy

Surgery

• Not specified