Intrathecal Rituximab in Treating Patients With Recurrent CNS Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00416923
First received: December 27, 2006
Last updated: October 1, 2012
Last verified: October 2012
  Purpose

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 Intervention Phase
Brain and Central Nervous System Tumors
Lymphoma
Biological: rituximab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Intrathecal Rituximab in Patients With Recurrent CNS Lymphoma

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Safety of intrathecal administration of Rituximab [ Time Frame: up to 5 years after completion of 5 week study treatment ] [ Designated as safety issue: Yes ]
    3 dose levels, 10 mg, 25 mg, 50 mg


Estimated Enrollment: 10
Study Start Date: August 2002
Estimated Study Completion Date: June 2013
Primary Completion Date: November 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: intrathecal rituximab
3 dose levels of intrathecal rituximab, 10mg, 25mg, 50mg
Biological: rituximab

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.

  Eligibility

Ages Eligible for Study:   17 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00416923

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

Additional Information:
Publications:
Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00416923     History of Changes
Other Study ID Numbers: CDR0000454842, UCSF-01302, UCSF-H9414-19588-04, UCSF-U2337S, GENENTECH-UCSF-01302
Study First Received: December 27, 2006
Last Updated: October 1, 2012
Health Authority: United States: Food and Drug Administration

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:
Lymphoma
Lymphoma, Non-Hodgkin
Nervous System Neoplasms
Lymphoma, Large-Cell, Immunoblastic
Central Nervous System Neoplasms
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Site
Nervous System Diseases
Rituximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 27, 2014