Intrathecal Rituximab in Treating Patients With Recurrent CNS Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving rituximab intrathecally may be an effective treatment for recurrent CNS lymphoma. PURPOSE: This phase I trial is studying the side effects and best dose of intrathecal rituximab in treating patients with recurrent CNS lymphoma.

Detailed Description
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OBJECTIVES: Primary Determine the safety and pharmacokinetics of intrathecal rituximab in patients with recurrent CNS lymphoma arising from CD20+ B-cell non-Hodgkin's lymphoma. Secondary Determine the efficacy of intrathecal rituximab. Determine the molecular pathogenesis of lymphomatous meningitis. Determine the molecular basis for response or lack of response to rituximab. Identify molecular markers specific for lymphomatous meningitis that will be useful for prognostic evaluation of peripheral lymphomas. Determine the quality of life of patients treated with intrathecal rituximab. OUTLINE: This is a dose-escalation, multicenter study. Patients receive rituximab intrathecally over 10 minutes on day 1 in week 1 and on days 1 and 4 in weeks 2-5 in the absence of disease progression or unacceptable toxicity. Patients achieving at least a partial response with no rituximab-related neurotoxicity may continue to receive treatment beyond 5 weeks. Cohorts of patients receive escalating doses of rituximab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which fewer than 1/3 of patients experience dose-limiting toxicity. Quality of life is assessed at baseline and at the completion of study treatment. After completion of study treatment, patients are followed periodically for 5 years. PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study.

Official Title
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Phase I Study of Intrathecal Rituximab in Patients With Recurrent CNS Lymphoma

Conditions
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Brain and Central Nervous System Tumors, Lymphoma

Intervention / Treatment
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* Biological: rituximab


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Cytologically confirmed relapsed CNS lymphoma Arising from primary CNS lymphoma or systemic non-Hodgkin's lymphoma Evidence of brain parenchymal involvement, cerebrospinal fluid (CSF) involvement, or ocular involvement after radiation treatment or intrathecal chemotherapy Tumors must be CD20+ on pathologic analysis Refractory or persistent disease allowed No complete obstruction of the CSF pathway within the ventricular system unless alleviated by external beam radiotherapy or systemic chemotherapy No obstructive hydrocephalus PATIENT CHARACTERISTICS: Karnofsky performance status > 50% Must have an Ommaya reservoir Granulocyte count > 1,500/mm^3 Platelet count > 50,000/mm^3 Anticipated survival ≥ 1 month PRIOR CONCURRENT THERAPY: See Disease Characteristics Recovered from toxicity of prior therapy Prior intrathecal methotrexate, cytarabine, or thiotepa for CNS lymphoma allowed Concurrent systemic chemotherapy for treatment of disease outside meninges allowed except for high-dose methotrexate, high-dose cytarabine, high-dose thiotepa, or investigational agents No history of whole-brain or craniospinal radiation < 1 week before study entry No history of intrathecal chemotherapy < 1 week before study entry No concurrent intrathecal chemotherapy

Ages Eligible for Study
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Minimum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: intrathecal rituximab<br>3 dose levels of intrathecal rituximab, 10mg, 25mg, 50mg | Biological: rituximab<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events as a measure of safety of intrathecal administration of Rituximab |  | up to 5 years after completion of 5 week study treatment | 
| Serum concentration of Rituximab |  | during 5 weeks of study treatment | 
| Cerebrospinal Fluid (CSF) concentration of Rituximab |  | during 5 weeks of study treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, stage IV adult Burkitt lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage IV mantle cell lymphoma, stage IV marginal zone lymphoma, stage IV small lymphocytic lymphoma, primary central nervous system non-Hodgkin lymphoma, leptomeningeal metastases, intraocular lymphoma, AIDS-related primary CNS lymphoma, Waldenström macroglobulinemia, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma