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