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

Phase 1
17 Years
Open (Enrolling)
Brain and Central Nervous System Tumors, Lymphoma

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Trial Information

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



- Determine the safety and pharmacokinetics of intrathecal rituximab in patients with
recurrent CNS lymphoma arising from CD20+ B-cell non-Hodgkin's lymphoma.


- 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.

Inclusion Criteria


- 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


- 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


- 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

Type of Study:


Study Design:

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

Outcome Measure:

Safety of intrathecal administration of Rituximab

Outcome Description:

3 dose levels, 10 mg, 25 mg, 50 mg

Outcome Time Frame:

up to 5 years after completion of 5 week study treatment

Safety Issue:


Principal Investigator

James L. Rubenstein, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of California, San Francisco


United States: Food and Drug Administration

Study ID:




Start Date:

August 2002

Completion Date:

June 2013

Related Keywords:

  • Brain and Central Nervous System Tumors
  • Lymphoma
  • 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
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Nervous System Neoplasms
  • Lymphoma, Large-Cell, Immunoblastic
  • Central Nervous System Neoplasms