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 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.