Trial Information

Phase I/II Study Of Pre-Irradiation Chemotherapy With Methotrexate, Rituximab, And Temozolomide And Post -Irradiation Temozolomide For Primary Central Nervous System Lymphoma

OBJECTIVES:

- Determine the maximum tolerated dose of temozolomide in combination with methotrexate
and rituximab before fractionated whole brain radiotherapy in patients with primary
central nervous system lymphoma.

- Compare the 2-year survival rate of patients receiving this chemotherapy regimen before
radiotherapy and temozolomide after radiotherapy to that of patients treated on
protocol RTOG-9310.

- Compare the tumor response rates of patients treated with this chemotherapy regimen
before radiotherapy to that of patients treated on Radiation Therapy Oncology Group
(RTOG), RTOG-9310.

- Determine the progression-free survival of patients treated with this regimen.

- Determine the acute and long-term neurologic toxicity of this regimen in these
patients.

- Determine the quality of life of patients treated with this regimen.

OUTLINE: This is a phase I dose-escalation study of temozolomide in combination with
methotrexate and rituximab before radiotherapy, followed by a phase II study.

Phase I

- Pre-radiotherapy chemotherapy: Patients receive rituximab IV 3 days prior to the first
course of methotrexate. Patients then receive methotrexate IV over 4 hours on weeks 1,
3, 5, 7, and 9 (for a total of 5 doses). Patients also receive oral temozolomide daily
for 5 days on weeks 4 and 8.

Cohorts of 3-6 patients receive escalating doses of temozolomide until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose at which no more than 0 of 3 or 1
of 6 patients experience dose-limiting toxicity.

- Radiotherapy: Patients undergo whole brain radiotherapy daily for 5 days on weeks 11,
12, and 13.

- Post-radiotherapy chemotherapy: Patients receive oral temozolomide once daily on days
1-5 beginning at week 14. Treatment repeats every 28 days for 10 courses in the absence
of unacceptable toxicity.

Phase II

- Patients receive treatment as in phase I at the MTD of temozolomide. Treatment
continues in the absence of unacceptable toxicity.

Quality of life is assessed at baseline, at weeks 10 and 13, every 2 months during
post-radiotherapy temozolomide therapy, at the end of therapy, every 3 months for 2 years,
every 6 months for 3 years, and then annually thereafter.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then
annually thereafter.

PROJECTED ACCRUAL: A total of 52-64 patients (up to 18 patients for phase I and 46 patients
for phase II) will be accrued for this study within 19 months.