A Phase I Study of Intrathecal Rituximab in Patients With Lymphomatous Meningitis

Study Overview
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Brief Summary
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The purpose of this study is to define the safety profile of rituximab given intrathecally in lymphomatous meningitis related to CD20+ non-Hodgkin's lymphomas.

Official Title
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A Phase I Study of Intrathecal Rituximab in Patients With Lymphomatous Meningitis

Conditions
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Lymphoma, B Cell

Intervention / Treatment
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* Drug: intrathecal rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Lymphomatous meningitis documented by positive CSF cytology in either newly diagnosed, relapsed or refractory primary CNS or systemic NHL Pathologically diagnosed CD20-positive NHL Age ≥ 18 years ECOG Performance Status 0 - 2 (See Appendix A) Life expectancy of at least 1 month Informed consent must be given according to national/local regulations before enrollment (See Appendix B) Patients may have had prior CNS irradiation, intrathecal methotrexate, cytarabine or thiotepa for treatment of lymphomatous meningitis but these treatments must have completed at least two weeks before the study enrollment and the patients must have recovered from any reversible toxicity caused by prior treatments Concurrent systemic chemotherapy is allowed with the exception of high-dose methotrexate (>500 mg/m2/day), high-dose cytarabine (>2 g/m2/day), high-dose thiotepa (>300 mg/m2/day) or investigational agents No concurrent intrathecal chemotherapy other than rituximab No severe impairment of bone marrow function (ANC >1.5x109/L, PLT >50x109/L), unless due to proven lymphoma involvement No major impairment of renal function (serum creatinine < 1,5 x upper normal) or liver function (ASAT/ALAT < 2,5 upper normal, total bilirubin <2,5x upper normal), unless due to proven lymphoma involvement No evidence of active opportunistic infections No HIV infection No pregnant or lactating status Appropriate contraceptive method in women of childbearing potential or men Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial Absence of a obstructive hydrocephalus or compartimentalization of CSF flow.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: intrathecal rituximab|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety profile of rituximab given intrathecally |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| preliminary evaluation of the antitumor activity of i.t. rituximab |  |  | 
| collection of CSF samples devoted to ancillary biological studies |  |  | 
| pharmacokinetics of different dose levels of intrathecal rituximab |  |  |