A Safety Study of Rituximab Plus MTX Injected Into the Cerebrospinal Fluid in the Treatment of Brain Lymphoma

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

Phase I Study of Intraventricular Administration of Rituximab in Combination With Methotrexate in the Treatment of Recurrent CNS and Intraocular Lymphoma

Rituximab is the first monoclonal antibody to receive approval in the treatment of cancer and has been proven to lead to extended survival when administered intravenously in the treatment of patients with systemic non-Hodgkin's lymphoma. We have previously demonstrated that a small fraction of Rituximab administered intravenously is able to cross the blood-brain-barrier into the brain.

We will test the idea that the direct injection into the cerebrospinal fluid of Rituximab, a monoclonal antibody which attacks and kills lymphoma cells, is safe and when used in combination with methotrexate in patients with recurrent brain and intraocular lymphoma.

We will also test the idea that the combination of rituximab plus methotrexate has activity and is effective in the treatment of recurrent brain and intraocular lymphoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Rituximab is the first monoclonal antibody to receive FDA approval in the treatment of cancer. Intravenous administration of rituximab has been demonstrated to lead to prolongation of survival when used in combination with chemotherapy in the treatment of patients with systemic non-Hodgkin's lymphoma. We have previously demonstrated that a small fraction of Rituximab administered intravenously is able to cross the blood-brain-barrier into the brain and we have also previously demonstrated that direct intraventricular administration of Rituximab is able to achieve high concentrations within the cerebrospinal fluid ventricles and lumbar sac.

We will test the hypothesis that the direct intraventricular injection of Rituximab in combination with Methotrexate is safe and when used in combination in patients with recurrent brain and intraocular lymphoma. We will evaluate the safety of this combination by testing different dose levels of Rituximab. We will also measure the concentration of Rituximab in the intraocular compartments and cerebrospinal fluid at different time points after intraventricular administration to determine the pharmacokinetics of intrathecal Rituximab as well as the potential impact of Methotrexate on Rituximab distribution.

We will also test the hypothesis that the intraventricular administration of the combination of rituximab plus methotrexate has activity and is effective in the treatment of recurrent brain and intraocular lymphoma.

Study Type

Interventional

Enrollment (Actual)

14

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94143
        • University of California, San Francisco
    • Massachusetts
      • Boston, Massachusetts, United States
        • Massachusetts General Hospital
    • New York
      • New York, New York, United States, 94123
        • Memorial Sloan-Kettering Cancer Center
    • Texas
      • Houston, Texas, United States
        • MD Anderson Cancer Center

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Relapsed, refractory CNS lymphoma, ocular lymphoma, lymphomatous meningitis
  2. Tumors must be CD20 + on pathologic analysis.
  3. Patients must have an Ommaya reservoir (ventricular access device.
  4. Patients may have had prior intrathecal methotrexate, ara-C or thiotepa but must have recovered from any reversible toxicity caused by prior treatment.
  5. Concurrent systemic chemotherapy is allowed for treatment of disease outside the meninges with the exception of high-dose methotrexate (>500 mg/m2/d, high-dose ara-C (> 2 gm/m2/d), high-dose thiotepa (>300 mg/m2/d) or investigational agents.
  6. Patients must have sufficient baseline hematologic function: >1,500 granulocytes and >50,000 platelets/ul.
  7. Patients must have had a nuclear medicine CSF flow study performed within 30 days of treatment which shows no significant obstruction within the ventricles.

Exclusion Criteria:

  1. History of whole brain or craniospinal irradiation or intrathecal chemotherapy < 4 days before initiation of intra-CSF administration of rituximab.
  2. Anticipated survival of less than one month.
  3. HIV infection. -

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: Rituximab Plus MTX
Drug: Intraventricular Rituximab Plus MTX

Intraventricular injection of rituximab into an Ommaya reservoir on day 1 of each week. Intraventricular rituximab plus methotrexate (MTX) on day 4 of each week.

First three patients at dose A : 25 mg rituximab on day 1, and MTX (12 mg) plus rituximab (10 mg) on day 4 each week.

If there are no dose limiting toxicities at Dose A in all of the first 3 patients or in 5 of the first 6 patients, the next 3 patients will receive dose level B: 25 mg rituximab on day 1, and combination MTX (12 mg) plus rituximab (25 mg) on day 4 of each week.

Oral leucovorin rescue 24 hours after each MTX administration. Maximum injections will be 16 over 9-weeks. Subjects who experience a partial response at week 10 will be given the option for extended dosing.

Other Names:
  • Rituxan
  • MabThera
  • amethopterin
  • MTX

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
whether intra-CSF administration of rituximab in combination with MTX in patients with recurrent CNS and intraocular lymphoma is associated with neurotoxicity
Time Frame: 4 weeks
4 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
To define the rate of tumor response (CR plus PR) in the brain, spine, eye, or CSF.
Time Frame: 4 weeks
4 weeks

Collaborators and Investigators

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

Sponsor

University of California, San Francisco

Investigators

  • Study Chair: 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

April 1, 2007

Primary Completion (Actual)

January 1, 2012

Study Completion (Actual)

March 1, 2013

Study Registration Dates

First Submitted

September 14, 2005

First Submitted That Met QC Criteria

September 14, 2005

First Posted (Estimate)

September 22, 2005

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

  • CC05254
  • H9414-29670

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.

Subscribe