Combination Chemotherapy, Monoclonal Antibody, and Radiation Therapy in Treating Patients With Primary Central Nervous System Lymphoma
- Conditions
- Brain and Central Nervous System TumorsLymphoma
- Interventions
- Registration Number
- NCT00068250
- Lead Sponsor
- Radiation Therapy Oncology Group
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 60
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase I: Temozolomide 150 mg temozolomide 150 mg/m^2 Rituximab, methotrexate, temozolomide 150 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2. Phase I: Temozolomide 200 mg temozolomide 200 mg/m^2 Rituximab, methotrexate, temozolomide 200 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2. Phase I: Temozolomide 200 mg post-radiation therapy temozolomide Rituximab, methotrexate, temozolomide 200 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2. Phase I: Temozolomide 150 mg post-radiation therapy temozolomide Rituximab, methotrexate, temozolomide 150 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2. Phase I: Temozolomide 100 mg post-radiation therapy temozolomide Rituximab, methotrexate, temozolomide 100 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2. Phase II: Temozolomide 100 mg temozolomide 100 mg/m^2 Rituximab, methotrexate, temozolomide 100 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2. Phase I: Temozolomide 100 mg temozolomide 100 mg/m^2 Rituximab, methotrexate, temozolomide 100 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2. Phase I: Temozolomide 200 mg radiation therapy Rituximab, methotrexate, temozolomide 200 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2. Phase II: Temozolomide 100 mg post-radiation therapy temozolomide Rituximab, methotrexate, temozolomide 100 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2. Phase I: Temozolomide 100 mg radiation therapy Rituximab, methotrexate, temozolomide 100 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2. Phase I: Temozolomide 150 mg radiation therapy Rituximab, methotrexate, temozolomide 150 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2. Phase II: Temozolomide 100 mg radiation therapy Rituximab, methotrexate, temozolomide 100 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2. Phase I: Temozolomide 100 mg rituximab Rituximab, methotrexate, temozolomide 100 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2. Phase I: Temozolomide 150 mg rituximab Rituximab, methotrexate, temozolomide 150 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2. Phase I: Temozolomide 100 mg methotrexate Rituximab, methotrexate, temozolomide 100 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2. Phase I: Temozolomide 150 mg methotrexate Rituximab, methotrexate, temozolomide 150 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2. Phase I: Temozolomide 200 mg rituximab Rituximab, methotrexate, temozolomide 200 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2. Phase I: Temozolomide 200 mg methotrexate Rituximab, methotrexate, temozolomide 200 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2. Phase II: Temozolomide 100 mg methotrexate Rituximab, methotrexate, temozolomide 100 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2. Phase II: Temozolomide 100 mg rituximab Rituximab, methotrexate, temozolomide 100 mg/m\^2, followed by radiation therapy, then post-radiation therapy temozolomide 200 mg/m\^2.
- Primary Outcome Measures
Name Time Method Phase II: Overall Survival Rate at 2 Years (Including Phase I Patients at Same Dose) Analysis occured after all patients have been on study for 2 years. Maximum follow-up at time of analysis was 8.5 years. Survival time is defined as time from registration to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. (Please note that this outcome measure is considered the primary endpoint for the Phase II component of the study, but that the patients from Phase I that were treated at the same dose level are included, as indicated in the treatment arm descriptions. )
Number of Phase I Participants Experiencing Toxicity From start of treatment to 10 weeks if radiation therapy received, to 15 weeks if not. A dose limiting toxicity (DLT) is defined as any grade 3 or 4 non-hematological toxicity (other than grade 3 nausea/vomiting) or any hematological toxicity resulting in the discontinuation of temozolomide. Toxicity evaluation for this dose escalation includes all toxicities occurring prior to the start of radiation therapy. If the patient did not receive radiation therapy, then toxicity evaluation included all toxicities occurring through week 15. Any grade 5 toxicity would result in immediate suspension of accrual.
- Secondary Outcome Measures
Name Time Method Phase II: Progression-free Survival (Including Phase I Patients at Same Dose) Analysis occured after all patients have been on study for 2 years. Maximum follow-up at time of analysis was 8.5 years. Progression is defined as greater than 25% increase in enhancing tumor or the appearance of new lesions in the brain, eye, or the appearance of a new positive cerebrospinal fluid (CSF) cytology. The patient may be neurologically stable or worse and on stable or increasing doses of corticosteroid. Progression-free survival time is defined as time from registration to the date of progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. (Please note that this outcome measure is considered a secondary endpoint for the Phase II component of the study, but that the patients from Phase I that were treated at the same dose level are included, as indicated in the treatment arm descriptions. )
Phase II: Pre-irradiation Chemotherapy Tumor Response Rate (Including Phase I Patients at Same Dose) From start of treatment to 10 weeks if RT received, to 15 weeks if not. Tumor response was centrally reviewed. Complete response: Disappearance of all enhancing tumor, the patient must be off steroid therapy and neurologically stable or improved; partial response: ≥ 50% decrease in enhancing tumor; progressive disease: ≥ 25% increase in a lesion, progressive or newly emergent meningeal or ocular disease. (Please note that this outcome measure is considered a secondary endpoint for the Phase II component of the study, but that the patients from Phase I that were treated at the same dose level are included, as indicated in the treatment arm descriptions. )
Trial Locations
- Locations (26)
Providence Milwaukie Hospital
🇺🇸Milwaukie, Oregon, United States
Baptist Cancer Institute - Jacksonville
🇺🇸Jacksonville, Florida, United States
Flagler Cancer Center
🇺🇸Saint Augustine, Florida, United States
Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
🇺🇸Murray, Utah, United States
Integrated Community Oncology Network at Southside Cancer Center
🇺🇸Jacksonville, Florida, United States
Baptist Medical Center South
🇺🇸Jacksonville, Florida, United States
Florida Cancer Center - Palatka
🇺🇸Palatka, Florida, United States
Integrated Community Oncology Network - Orange Park
🇺🇸Orange Park, Florida, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
🇺🇸Saint Louis, Missouri, United States
Utah Valley Regional Medical Center - Provo
🇺🇸Provo, Utah, United States
Community Memorial Hospital Cancer Care Center
🇺🇸Menomonee Falls, Wisconsin, United States
Integrated Community Oncology Network
🇺🇸Jacksonville Beach, Florida, United States
Borgess Medical Center
🇺🇸Kalamazoo, Michigan, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Cleveland Clinic Taussig Cancer Center
🇺🇸Cleveland, Ohio, United States
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
John F. Kennedy Medical Center
🇺🇸Edison, New Jersey, United States
CCOP - Nevada Cancer Research Foundation
🇺🇸Las Vegas, Nevada, United States
Providence Cancer Center at Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
CCOP - Columbia River Oncology Program
🇺🇸Portland, Oregon, United States
Providence St. Vincent Medical Center
🇺🇸Portland, Oregon, United States
Southwest Washington Medical Center Cancer Center
🇺🇸Vancouver, Washington, United States
CCOP - Kansas City
🇺🇸Kansas City, Missouri, United States
Hollings Cancer Center at Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Medical College of Wisconsin Cancer Center
🇺🇸Milwaukee, Wisconsin, United States