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Intrathecal Rituximab in Treating Patients With Recurrent CNS Lymphoma

Primary Purpose

Brain and Central Nervous System Tumors, Lymphoma

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
rituximab
Sponsored by
University of California, San Francisco
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring 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

Eligibility Criteria

17 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    intrathecal rituximab

    Arm Description

    3 dose levels of intrathecal rituximab, 10mg, 25mg, 50mg

    Outcomes

    Primary Outcome Measures

    Adverse events as a measure of safety of intrathecal administration of Rituximab
    Serum concentration of Rituximab
    Cerebrospinal Fluid (CSF) concentration of Rituximab

    Secondary Outcome Measures

    Full Information

    First Posted
    December 27, 2006
    Last Updated
    February 12, 2015
    Sponsor
    University of California, San Francisco
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00416923
    Brief Title
    Intrathecal Rituximab in Treating Patients With Recurrent CNS Lymphoma
    Official Title
    Phase I Study of Intrathecal Rituximab in Patients With Recurrent CNS Lymphoma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2015
    Overall Recruitment Status
    Completed
    Study Start Date
    August 2002 (undefined)
    Primary Completion Date
    November 2005 (Actual)
    Study Completion Date
    April 2007 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University of California, San Francisco

    4. Oversight

    5. Study Description

    Brief Summary
    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
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Brain and Central Nervous System Tumors, Lymphoma
    Keywords
    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

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    10 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    intrathecal rituximab
    Arm Type
    Experimental
    Arm Description
    3 dose levels of intrathecal rituximab, 10mg, 25mg, 50mg
    Intervention Type
    Biological
    Intervention Name(s)
    rituximab
    Primary Outcome Measure Information:
    Title
    Adverse events as a measure of safety of intrathecal administration of Rituximab
    Time Frame
    up to 5 years after completion of 5 week study treatment
    Title
    Serum concentration of Rituximab
    Time Frame
    during 5 weeks of study treatment
    Title
    Cerebrospinal Fluid (CSF) concentration of Rituximab
    Time Frame
    during 5 weeks of study treatment

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    17 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    James L. Rubenstein, MD, PhD
    Organizational Affiliation
    University of California, San Francisco
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    17312328
    Citation
    Rubenstein JL, Fridlyand J, Abrey L, Shen A, Karch J, Wang E, Issa S, Damon L, Prados M, McDermott M, O'Brien J, Haqq C, Shuman M. Phase I study of intraventricular administration of rituximab in patients with recurrent CNS and intraocular lymphoma. J Clin Oncol. 2007 Apr 10;25(11):1350-6. doi: 10.1200/JCO.2006.09.7311. Epub 2007 Feb 20.
    Results Reference
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    Intrathecal Rituximab in Treating Patients With Recurrent CNS Lymphoma

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