This phase I/II trial studies the side effects of methotrexate, mannitol, rituximab, and carboplatin and to see how well they work in treating patients with primary central nervous system lymphoma. Drugs used in chemotherapy, such as methotrexate and carboplatin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Osmotic blood-brain barrier disruption uses mannitol to open the blood vessels around the brain and allow cancer-killing substances to be carried directly to the brain. Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Giving methotrexate, mannitol, rituximab, and carboplatin together may be an effective treatment for primary central nervous system lymphoma.
PRIMARY OBJECTIVES: I. To evaluate the safety and toxicities of a treatment regimen consisting of rituximab (intravenously \[IV\]) the day prior to methotrexate (intra-arterially \[IA\]), and carboplatin (IA) in conjunction with blood-brain barrier disruption (BBBD) and delayed sodium thiosulfate (IV). II. To demonstrate, adding a monoclonal antibody and carboplatin to methotrexate BBBD, that a 45% rate of complete response (CR) within the first 3 months of treatment is achieved, while excluding a CR rate as low as 30%. SECONDARY OBJECTIVE: I. To estimate the response rate (counting all CRs), the two-year overall survival and the two-year event-free survival, as baselines for subsequent trials. OUTLINE: Patients receive rituximab IV over 5 hours on day 1, mannitol IA, methotrexate IA over 10 minutes, and carboplatin IA over 10 minutes on days 2 and 3. Patients then receive sodium thiosulfate IV over 15 minutes at 4 and 8 hours after carboplatin. Treatment repeats monthly for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 2 months, then every 2 months for 2 years, every 6 months for 1 year, and then annually for at least 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
81
Given IA
Given IA
Given IA
Ancillary studies
Given IV
Given IV
Good Samaritan Hospital - Cincinnati
Cincinnati, Ohio, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
OHSU Knight Cancer Institute
Portland, Oregon, United States
Incidence of toxicities, assessed using National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0 (Phase I)
Time frame: Within 2 months of completion of study treatment
CR rate (Phase II)
Time frame: Within the first 3 months of treatment
Overall survival
Kaplan-Meier estimates of these survival distributions will be plotted. Descriptive stratifications of these survival distributions by baseline characteristics will be evaluated using the log-rank statistic. If there are multiple predictors of these outcomes, Cox proportional hazard models will be fit to these data to determine which predictors are independent of others in a multi-variable model.
Time frame: From entry onto study until death from any cause, assessed at 2 years
Event-free survival
Kaplan-Meier estimates of these survival distributions will be plotted. Descriptive stratifications of these survival distributions by baseline characteristics will be evaluated using the log-rank statistic. If there are multiple predictors of these outcomes, Cox proportional hazard models will be fit to these data to determine which predictors are independent of others in a multi-variable model.
Time frame: From entry onto study until death or progression of disease, assessed at 2 years
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