A PHASE II TRIAL OF RITUXAN IN MULTIPLE SCLEROSIS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Rituxan (Genetech) is a humanized monoclonal antibody directed against the B-cell specific antigen, CD20. It has been used for several years in the therapy of non-Hodgkin's lymphoma. There is experience using this agent in several hundred human subjects, but not in MS patients. The agent will be administered intravenously in 4 doses, one week apart of 375mg/m2. This dose eliminates circulating B cells completely for up to 6 months following therapy. There is considerable data that B cells and/or antibody may be involved in the jpathogenesis of MS. However, to determine whether B cells truly play a role will require an assessment of whether their eliminiation benefits the course of MS. Therefore, as a first step we propose a 30 patient, Phase II trial of the safety and efficacy of Rituxan in 30 patients with active, relapsing MS. Patients will continue taking the standard dose of beta-interferon while in the trial. Subjects enrolled in the trial must have evidence of two gadolinium0enhacing lesions on any of three pre-treatment brain MRIs, and will have had at least one clinical relapse in the 18months prior to enrollment, despite being on beta-interferon therapy. The endpoints will be safety, in terms of toxicity of the agent and the possibility of worsening of MS, and efficacy based on the surrogate measure of MRI activity. The primary efficacy endpoint will be reduction in volume of gadolinium-enhancing lesions on the 3-once-monthly brain MRIs performed post-treatment in comparison to the three once-monthly MRIs performed pre-treatment.