Intrathecal Rituximab in Treating Patients With Recurrent CNS Lymphoma

University of California San Francisco (UCSF)

Status and phase

Completed

Phase 1

Conditions

Brain and Central Nervous System Tumors

Lymphoma

Treatments

Biological: rituximab

Study type

Interventional

Funder types

Other

Identifiers

NCT00416923

UCSF-01302

CDR0000454842

UCSF-H9414-19588-04

GENENTECH-UCSF-01302

UCSF-U2337S

Details and patient eligibility

About

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.

Full 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.

Enrollment

10 estimated patients

Sex

All

Ages

17+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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