Intrathecal Rituximab in Treating Patients With Recurrent CNS Lymphoma

NCT ID: NCT00416923

Last Updated: 2015-02-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-08-31
• Study Completion Date: 2007-04-30

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.

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.

Conditions

Brain and Central Nervous System Tumors; Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

intrathecal rituximab

3 dose levels of intrathecal rituximab, 10mg, 25mg, 50mg

Group Type: EXPERIMENTAL

rituximab

Intervention Type: BIOLOGICAL

Interventions

rituximab

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

James L. Rubenstein, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

References

Rubenstein JL, Fridlyand J, Abrey L, Shen A, Karch J, Wang E, Issa S, Damon L, Prados M, McDermott M, O'Brien J, Haqq C, Shuman M. Phase I study of intraventricular administration of rituximab in patients with recurrent CNS and intraocular lymphoma. J Clin Oncol. 2007 Apr 10;25(11):1350-6. doi: 10.1200/JCO.2006.09.7311. Epub 2007 Feb 20.

Reference Type: RESULT

PMID: 17312328 (View on PubMed)

Other Identifiers

UCSF-01302

Identifier Type: -

Identifier Source: secondary_id

UCSF-H9414-19588-04

Identifier Type: -

Identifier Source: secondary_id

UCSF-U2337S

Identifier Type: -

Identifier Source: secondary_id

GENENTECH-UCSF-01302

Identifier Type: -

Identifier Source: secondary_id

CDR0000454842

Identifier Type: -

Identifier Source: org_study_id