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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety of intrathecal administration of Rituximab
3 dose levels, 10 mg, 25 mg, 50 mg
up to 5 years after completion of 5 week study treatment
James L. Rubenstein, MD, PhD
University of California, San Francisco
United States: Food and Drug Administration