Intrathecal Rituximab in Treating Patients With Recurrent CNS Lymphoma

February 12, 2015 updated by: University of California, San Francisco

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

10

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

17 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
up to 5 years after completion of 5 week study treatment
Serum concentration of Rituximab
Time Frame: during 5 weeks of study treatment
during 5 weeks of study treatment
Cerebrospinal Fluid (CSF) concentration of Rituximab
Time Frame: during 5 weeks of study treatment
during 5 weeks of study treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Investigators

  • Principal Investigator: James L. Rubenstein, MD, PhD, University of California, San Francisco

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2002

Primary Completion (Actual)

November 1, 2005

Study Completion (Actual)

April 1, 2007

Study Registration Dates

First Submitted

December 27, 2006

First Submitted That Met QC Criteria

December 27, 2006

First Posted (Estimate)

December 28, 2006

Study Record Updates

Last Update Posted (Estimate)

February 16, 2015

Last Update Submitted That Met QC Criteria

February 12, 2015

Last Verified

February 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000454842
  • UCSF-01302
  • UCSF-H9414-19588-04
  • UCSF-U2337S
  • GENENTECH-UCSF-01302

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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