Intrathecal Rituximab in Treating Patients With Recurrent CNS Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00416923
Recruitment Status : Completed
First Posted : December 28, 2006
Last Update Posted : February 16, 2015
Information provided by (Responsible Party):
University of California, San Francisco

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.

Condition or disease Intervention/treatment Phase
Brain and Central Nervous System Tumors Lymphoma Biological: rituximab Phase 1

Detailed Description:



  • Determine the safety and pharmacokinetics of intrathecal rituximab in patients with recurrent CNS lymphoma arising from CD20+ B-cell non-Hodgkin's lymphoma.


  • 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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Intrathecal Rituximab in Patients With Recurrent CNS Lymphoma
Study Start Date : August 2002
Actual Primary Completion Date : November 2005
Actual Study Completion Date : April 2007

Arm Intervention/treatment
Experimental: intrathecal rituximab
3 dose levels of intrathecal rituximab, 10mg, 25mg, 50mg
Biological: rituximab

Primary Outcome Measures :
  1. 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 ]
  2. Serum concentration of Rituximab [ Time Frame: during 5 weeks of study treatment ]
  3. Cerebrospinal Fluid (CSF) concentration of Rituximab [ Time Frame: during 5 weeks of study treatment ]

Information from the National Library of Medicine

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Ages Eligible for Study:   17 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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


  • 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


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00416923

Sponsors and Collaborators
University of California, San Francisco
Principal Investigator: James L. Rubenstein, MD, PhD University of California, San Francisco

Publications of Results:
Responsible Party: University of California, San Francisco Identifier: NCT00416923     History of Changes
Other Study ID Numbers: CDR0000454842
First Posted: December 28, 2006    Key Record Dates
Last Update Posted: February 16, 2015
Last Verified: February 2015

Keywords provided by University of California, San Francisco:
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

Additional relevant MeSH terms:
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Site
Nervous System Diseases
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents