Clinical Trial: A Safety Study of Rituximab Plus MTX Injected Into the Cerebrospinal Fluid in the Treatment of Brain Lymphoma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief Summary:

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.

Detailed Summary:

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.

Sponsor: University of California, San Francisco

Current Primary Outcome: whether intra-CSF administration of rituximab in combination with MTX in patients with recurrent CNS and intraocular lymphoma is associated with neurotoxicity [ Time Frame: 4 weeks ]

Original Primary Outcome:

Current Secondary Outcome: To define the rate of tumor response (CR plus PR) in the brain, spine, eye, or CSF. [ Time Frame: 4 weeks ]

Original Secondary Outcome:

Information By: University of California, San Francisco

Dates:
Date Received: September 14, 2005
Date Started: April 2007
Date Completion:
Last Updated: February 12, 2015
Last Verified: February 2015