Intrathecal Rituximab in Treating Patients With Recurrent CNS Lymphoma

Sponsor

University of California, San Francisco (Other)

Overall Status

Completed

CT.gov ID

NCT00416923

Collaborator

(none)

Enrollment

Arm

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors Lymphoma	Biological: rituximab	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Aug 1, 2002

Actual Primary Completion Date :

Nov 1, 2005

Actual Study Completion Date :

Apr 1, 2007

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: intrathecal rituximab

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

Biological: rituximab

Outcome Measures

Primary Outcome Measures

Adverse events as a measure of safety of intrathecal administration of Rituximab [up to 5 years after completion of 5 week study treatment]
Serum concentration of Rituximab [during 5 weeks of study treatment]
Cerebrospinal Fluid (CSF) concentration of Rituximab [during 5 weeks of study treatment]

Eligibility Criteria

Criteria

Ages Eligible for Study:

17 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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