A Safety Study of Rituximab Plus MTX Injected Into the Cerebrospinal Fluid in the Treatment of Brain Lymphoma
A Safety Study of Rituximab Plus MTX Injected Into the Cerebrospinal Fluid in the Treatment of Brain Lymphoma
Rituximab is the first monoclonal antibody to receive approval in the treatment of cancer and
 has been proven to lead to extended survival when administered intravenously 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.

 We will test the idea that the direct injection into the cerebrospinal fluid of Rituximab, a
 monoclonal antibody which attacks and kills lymphoma cells, is safe and when used in
 combination with methotrexate in patients with recurrent brain and intraocular lymphoma.

 We will also test the idea that the combination of rituximab plus methotrexate has activity
 and is effective in the treatment of recurrent brain 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. -