Intrathecal Rituximab in Treating Patients With Recurrent CNS Lymphoma

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00416923
• Other study ID #: CDR0000454842
• Secondary ID: UCSF-01302UCSF-H
• Status: Completed
• Phase: Phase 1
• First received: December 27, 2006
• Last updated: February 12, 2015
• Start date: August 2002
• Est. completion date: April 2007

Study information

• Verified date: February 2015
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: April 2007
• Est. primary completion date: November 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 17 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Lymphoma
• Nervous System Neoplasms

Intervention

Biological:
• rituximab

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Francisco

References & Publications (1)

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 Cli — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events as a measure of safety of intrathecal administration of Rituximab		up to 5 years after completion of 5 week study treatment	Yes
Primary	Serum concentration of Rituximab		during 5 weeks of study treatment	Yes
Primary	Cerebrospinal Fluid (CSF) concentration of Rituximab		during 5 weeks of study treatment	Yes