Clinical trial NCT00416923: Intrathecal Rituximab in Treating Patients With Recurrent CNS Lymphoma
Official title: Phase I Study of Intrathecal Rituximab in Patients With Recurrent CNS Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Brain and Central Nervous System Tumors
Lymphoma
Keywords: recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
stage IV adult Burkitt lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV mantle cell lymphoma
stage IV marginal zone lymphoma
stage IV small lymphocytic lymphoma
primary central nervous system non-Hodgkin lymphoma
leptomeningeal metastases
intraocular lymphoma
AIDS-related primary CNS lymphoma
Waldenström macroglobulinemia
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2006-12-28
Enrollment: 10
Sex: ALL
Minimum age (years): 17
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Adverse events as a measure of safety of intrathecal administration of Rituximab
timeFrame: up to 5 years after completion of 5 week study treatment
measure: Serum concentration of Rituximab
timeFrame: during 5 weeks of study treatment
measure: Cerebrospinal Fluid (CSF) concentration of Rituximab
timeFrame: during 5 weeks of study treatment
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: University of California, San Francisco
name: James L. Rubenstein, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.