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Phase I Study of Intraventricular Administration of Rituximab in Combination With Methotrexate in the Treatment of Recurrent CNS and Intraocular Lymphoma

Phase 1
18 Years
Open (Enrolling)
Central Nervous System Lymphoma, Intraocular Lymphoma

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Trial Information

Phase I Study of Intraventricular Administration of Rituximab in Combination With Methotrexate in the Treatment of Recurrent CNS and Intraocular Lymphoma

Rituximab is the first monoclonal antibody to receive FDA approval in the treatment of
cancer. Intravenous administration of rituximab has been demonstrated to lead to
prolongation of survival when used in combination with chemotherapy in the treatment of
patients with systemic non-Hodgkin's lymphoma. We have previously demonstrated that a small
fraction of Rituximab administered intravenously is able to cross the blood-brain-barrier
into the brain and we have also previously demonstrated that direct intraventricular
administration of Rituximab is able to achieve high concentrations within the cerebrospinal
fluid ventricles and lumbar sac.

We will test the hypothesis that the direct intraventricular injection of Rituximab in
combination with Methotrexate is safe and when used in combination in patients with
recurrent brain and intraocular lymphoma. We will evaluate the safety of this combination
by testing different dose levels of Rituximab. We will also measure the concentration of
Rituximab in the intraocular compartments and cerebrospinal fluid at different time points
after intraventricular administration to determine the pharmacokinetics of intrathecal
Rituximab as well as the potential impact of Methotrexate on Rituximab distribution.

We will also test the hypothesis that the intraventricular administration of the combination
of rituximab plus methotrexate has activity and is effective in the treatment of recurrent
brain and intraocular lymphoma.

Inclusion Criteria:

1. Relapsed, refractory CNS lymphoma, ocular lymphoma, lymphomatous meningitis

2. Tumors must be CD20 + on pathologic analysis.

3. Patients must have an Ommaya reservoir (ventricular access device.

4. Patients may have had prior intrathecal methotrexate, ara-C or thiotepa but must have
recovered from any reversible toxicity caused by prior treatment.

5. Concurrent systemic chemotherapy is allowed for treatment of disease outside the
meninges with the exception of high-dose methotrexate (>500 mg/m2/d, high-dose ara-C
(> 2 gm/m2/d), high-dose thiotepa (>300 mg/m2/d) or investigational agents.

6. Patients must have sufficient baseline hematologic function: >1,500 granulocytes and
>50,000 platelets/ul.

7. Patients must have had a nuclear medicine CSF flow study performed within 30 days of
treatment which shows no significant obstruction within the ventricles.

Exclusion Criteria:

1. History of whole brain or craniospinal irradiation or intrathecal chemotherapy < 4
days before initiation of intra-CSF administration of rituximab.

2. Anticipated survival of less than one month.

3. HIV infection. -

Type of Study:


Study Design:

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

Outcome Measure:

whether intra-CSF administration of rituximab in combination with MTX in patients with recurrent CNS and intraocular lymphoma is associated with neurotoxicity

Outcome Time Frame:

4 weeks

Safety Issue:


Principal Investigator

James L. Rubenstein, MD PhD

Investigator Role:

Study Chair

Investigator Affiliation:

University of California, San Francisco


United States: Food and Drug Administration

Study ID:




Start Date:

April 2007

Completion Date:

April 2013

Related Keywords:

  • Central Nervous System Lymphoma
  • Intraocular Lymphoma
  • Phase I Clinical Trial
  • Pharmacokinetics
  • Pharmacodynamics
  • CNS Lymphoma
  • Ocular Lymphoma
  • Lymphoma



MD Anderson Cancer Center Houston, Texas  77030-4096
Memorial Sloan-Kettering Cancer Center New York, New York  10021
Massachusetts General Hospital Boston, Massachusetts  02114-2617
University of California, San Francisco San Francisco, California  94143