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

Radiation Therapy Oncology Group

Status and phase: Completed; Phase 2; Phase 1

Conditions: Brain and Central Nervous System Tumors; Lymphoma

Treatments: Drug: post-radiation therapy temozolomide; Drug: rituximab; Drug: temozolomide 100 mg/m^2; Drug: temozolomide 150 mg/m^2; Drug: methotrexate; Drug: temozolomide 200 mg/m^2; Radiation: radiation therapy

Study type: Interventional

Funder types: Other; NETWORK; NIH

Identifiers

NCT00068250

RTOG-0227

CDR0000301563

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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60 participants in 4 patient groups

Phase I: Temozolomide 100 mg

Experimental group

Description:

Rituximab, methotrexate, temozolomide 100 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2.

Treatment:

Radiation: radiation therapy

Drug: temozolomide 100 mg/m^2

Drug: methotrexate

Drug: rituximab

Drug: post-radiation therapy temozolomide

Phase I: Temozolomide 150 mg

Experimental group

Description:

Rituximab, methotrexate, temozolomide 150 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2.

Treatment:

Radiation: radiation therapy

Drug: methotrexate

Drug: rituximab

Drug: post-radiation therapy temozolomide

Drug: temozolomide 150 mg/m^2

Phase I: Temozolomide 200 mg

Experimental group

Description:

Rituximab, methotrexate, temozolomide 200 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2.

Treatment:

Radiation: radiation therapy

Drug: methotrexate

Drug: temozolomide 200 mg/m^2

Drug: rituximab

Drug: post-radiation therapy temozolomide

Phase II: Temozolomide 100 mg

Experimental group

Description:

Rituximab, methotrexate, temozolomide 100 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2.

Treatment:

Radiation: radiation therapy

Drug: temozolomide 100 mg/m^2

Drug: methotrexate

Drug: rituximab

Drug: post-radiation therapy temozolomide