Trial Information

Intensive Chemotherapy And Immunotherapy In 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.