Combination Chemotherapy, Monoclonal Antibody, and Radiation Therapy in Treating Patients With Primary Central Nervous System Lymphoma

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.

Conditions

• Brain and Central Nervous System Tumors
• Lymphoma

Interventions

DRUG

rituximab

375 mg/m2, intravenously three days prior to the first cycle of methotrexate

DRUG

methotrexate

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.

DRUG

temozolomide 100 mg/m^2

Temozolomide 100 mg/m\^2 by mouth per day for five days on weeks 4 and 8.

DRUG

temozolomide 150 mg/m^2

Temozolomide 150 mg/m\^2 by mouth per day for five days on weeks 4 and 8.

DRUG

temozolomide 200 mg/m^2

Temozolomide 200 mg/m\^2 per day by mouth for five days on weeks 4 and 8.

RADIATION

radiation therapy

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.

DRUG

post-radiation therapy temozolomide

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.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• NRG Oncology

  collaborator OTHER

• Radiation Therapy Oncology Group

  lead NETWORK

Principal Investigators

• Jon Glass, MD · Sidney Kimmel Cancer Center at Thomas Jefferson University

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2003-07-31

Primary Completion

2016-12-31

Completion

2016-12-31

Countries

• United States

Study Locations