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

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.

Inclusion criteria:

1. Primary central nervous system (CNS) lymphoma [B-cell, Cluster of Differentiation 20
(CD20) antigen positive] based on positive biopsy or cerebrospinal fluid (CSF) or
vitreous cytology (in association with measurable intraparenchymal tumor). Cytology
must demonstrate lymphoma or have an immunohistochemical diagnosis of malignant
lymphocytes with a monoclonal lymphocytic population.

2. Life expectancy ≥ 8 weeks;

3. Zubrod performance status of 0-2;

4. Absolute granulocyte count ≥1500/mm3; platelet count ≥ 100,000/mm3; creatinine
clearance ≥ 50, calculated with the Cockcroft-Gault Equation: Cr Clearance = (140-age)
x wt (kg)/(Cr[mg/dl]x 72); Bilirubin, serum glutamate oxaloacetate transaminase
(SGOT), alkaline phosphatase (AST) ≤ 2 x institutional upper limits of normal;

5. Patients must sign a study-specific informed consent prior to study entry.

6. Age ≥ 18

Exclusion criteria:

1. Evidence of systemic lymphoma;

2. Prior malignancy (excluding in situ carcinoma of the cervix or non-melanomatous skin
cancer)unless disease free for at least five years;

3. Prior radiotherapy to the brain or head/neck;

4. Prior chemotherapy;

5. History of idiopathic sensitivity to any of the drugs to be used;

6. Active infectious process;

7. Seropositive for HIV, AIDS, or post-organ transplant;

8. Pregnant women are ineligible as treatment involves unforeseeable risks to the
participant and to the embryo or fetus.

9. Active hepatitis B.