Clinical trial NCT00068250
Conditions: Brain and Central Nervous System Tumors Lymphoma
Keywords: primary central nervous system non-Hodgkin lymphoma primary central nervous system Hodgkin lymphoma
Sponsor: Radiation Therapy Oncology Group
Start date: 2003-07-01; Completion date: 2016-12-01
Enrollment: 60 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
RATIONALE: Drugs used in chemotherapy such as methotrexate and temozolomide use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Radiation therapy uses high-energy x-rays to damage cancer cells. Combining methotrexate, temozolomide, and rituximab with radiation therapy may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of temozolomide when given together with methotrexate and rituximab followed by radiation therapy and to see how well they work in treating patients with primary central nervous system lymphoma.

Detailed description:
OBJECTIVES:

* To assess the maximum tolerated dose (MTD) of temozolomide (TMZ) in combination with methotrexate (MTX) and rituximab (RTX) when administered prior to twice daily fractionated whole brain radiation therapy (WBRT) in patients with primary central nervous system lymphoma.
* To compare the two-year survival rate in patients receiving pre-irradiation chemotherapy, twice daily fractionated whole brain radiation therapy and post-irradiation temozolomide to the reported two-year survival rate of Radiation Therapy Oncology Group (RTOG) trial 93-10. RTOG 9310 does not fall within ClinicalTrials.gov registration/reporting requirements.)
* To compare the pre-irradiation chemotherapy tumor response rates to the reported rate from RTOG 93-10.
* To report progression-free survival.
* To assess acute and long-term neurologic toxicity, and to collect quality of life data for this patient group.

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

Arms: arm 1: Rituximab, methotrexate, temozolomide 100 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2. arm 2: Rituximab, methotrexate, temozolomide 150 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2. arm 3: Rituximab, methotrexate, temozolomide 200 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2. arm 4: Rituximab, methotrexate, temozolomide 100 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2.
Interventions: intervention 1: rituximab intervention 2: methotrexate intervention 3: temozolomide 100 mg/m^2 intervention 4: temozolomide 150 mg/m^2 intervention 5: temozolomide 200 mg/m^2 intervention 6: radiation therapy intervention 7: post-radiation therapy temozolomide
Intervention descriptions: intervention 1: 375 mg/m2, intravenously three days prior to the first cycle of methotrexate intervention 2: Five cycles of methotrexate (MTX) at 3.5 gm/m2 administered every two weeks on weeks 1, 3, 5, 7, and 9 via intravenous infusion over four hours once per cycle. Calcium leucovorin 25 mg orally or intravenously every six hours initiated exactly 24 hours following the start of the MTX infusion. Methotrexate levels to be monitored daily, and calcium leucovorin discontinued when the MTX level is less than 10 micromolar. intervention 3: Temozolomide 100 mg/m\^2 by mouth per day for five days on weeks 4 and 8. intervention 4: Temozolomide 150 mg/m\^2 by mouth per day for five days on weeks 4 and 8. intervention 5: Temozolomide 200 mg/m\^2 per day by mouth for five days on weeks 4 and 8. intervention 6: Whole brain irradiation (WBRT) during weeks 11, 12, and 13, five days per week (excluding weekends). A daily dose of 2.4 Gy delivered in two fractions of 1.2 Gy each with a minimum inter-fraction interval of 6 hours, with a total dose to brain and meninges of 36 Gy. intervention 7: Temozolomide (TMZ) 200 mg/m\^2 by mouth per day for 5 days on weeks 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 for a total of 10 cycles.

Protocol documents: