Intrathecal Rituximab in Treating Patients With Recurrent CNS Lymphoma

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.

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