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

Sponsor:	University of California, San Francisco
Information provided by:	University of California, San Francisco
ClinicalTrials.gov Identifier:	NCT00221325

Purpose

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.

Condition	Intervention	Phase
Central Nervous System Lymphoma Intraocular Lymphoma	Drug: Intraventricular Rituximab Plus MTX	Phase I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Dose Comparison, Single Group Assignment, Safety Study
Official Title:	Phase I Study of Intraventricular Administration of Rituximab in Combination With Methotrexate in the Treatment of Recurrent CNS and Intraocular Lymphoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Methotrexate Rituximab

U.S. FDA Resources

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

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To define the rate of tumor response (CR plus PR) in the brain, spine, eye, or CSF. [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	April 2007
Estimated Study Completion Date:	April 2013
Estimated Primary Completion Date:	April 2011 (Final data collection date for primary outcome measure)

Intervention Details:

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.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Relapsed, refractory CNS lymphoma, ocular lymphoma, lymphomatous meningitis
Tumors must be CD20 + on pathologic analysis.
Patients must have an Ommaya reservoir (ventricular access device.
Patients may have had prior intrathecal methotrexate, ara-C or thiotepa but must have recovered from any reversible toxicity caused by prior treatment.
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.
Patients must have sufficient baseline hematologic function: >1,500 granulocytes and >50,000 platelets/ul.
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:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00221325

Contacts

Contact: James L. Rubenstein, MD, PhD

415-502-4430

jamesr@medicine.ucsf.edu

Locations

United States, California
University of California, San Francisco	Recruiting
San Francisco, California, United States, 94143
Contact: James L Rubenstein, MD, PhD 415-502-4430 jamesr@medicine.ucsf.edu
United States, Massachusetts
Massachusetts General Hospital	Not yet recruiting
Boston, Massachusetts, United States
Contact: Tracy Batchelor, MD
United States, New York
Memorial Sloan-Kettering Cancer Center	Not yet recruiting
New York, New York, United States, 94123
Contact: Lauren Abrey, MD
United States, Texas
MD Anderson Cancer Center	Not yet recruiting
Houston, Texas, United States

Sponsors and Collaborators

University of California, San Francisco

Investigators

Study Chair:

James L. Rubenstein, MD PhD

University of California, San Francisco

More Information

No publications provided

Responsible Party:	University of California San Francisco ( James Rubenstein, MD, PhD )
Study ID Numbers:	CC05254, H9414-29670
Study First Received:	September 14, 2005
Last Updated:	June 18, 2008
ClinicalTrials.gov Identifier:	NCT00221325 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of California, San Francisco:

Phase I Clinical Trial
Pharmacokinetics
Pharmacodynamics
CNS Lymphoma
Ocular Lymphoma

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Immunoproliferative Disorders
Immune System Diseases
Immunologic Factors
Antineoplastic Agents
Rituximab
Physiological Effects of Drugs

Pharmacologic Actions
Lymphatic Diseases
Neoplasms
Therapeutic Uses
Lymphoproliferative Disorders
Antirheumatic Agents
Lymphoma

ClinicalTrials.gov processed this record on February 08, 2010