A Pilot Trial of Rituxan in Refractory Myasthenia Gravis
Myasthenia gravis is a disease that happens because the immune system attacks the nervous system. The damage is caused by antibodies produced by B lymphocytes. These antibodies damage a special part of the muscle that helps transmit impulses from nerves to muscles to allow muscles to work properly. This damage results in symptoms of myasthenia gravis. Participants are being asked to participate in this research study because their myasthenia gravis has either failed to respond to treatments commonly used in the disease, or they have had bad side-effects from such treatments.
This is a research study of a drug called Rituximab. Rituximab, also called Rituxan, is a mouse antibody that has been changed to make it similar to a human antibody. Antibodies are proteins that can protect the body from foreign invaders, such as bacteria and viruses, by binding to substances called antigens. Rituxan works by binding to a protein, called the CD20 protein. Rituxan helps to destroy white blood cells that produce antibodies in the body, called B-lymphocytes. It is a treatment given through a vein in the participant's arm over a period of approximately 4-6 hours. It has been approved by the Food and Drug Administration (FDA) for use in patients with a form of cancer of the lymph glands called Non-Hodgkin's Lymphoma (NHL). Rituximab is not approved for their myasthenia gravis.
Treatment with Rituximab is being tried in this research study because Rituximab decreases B lymphocytes. There is preliminary evidence that Rituximab helps some patients with chronic and otherwise difficult to treat myasthenia gravis.
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase 1-2 Pilot Study of Rituximab (Rituxan) in Refractory Myasthenia Gravis.|
- To examine the effects of rituximab on disease activity in MG patients with refractory disease. [ Time Frame: Patients will be followed for one year ] [ Designated as safety issue: No ]
- To determine the safety and tolerability of rituximab in MG patients with refractory disease. [ Time Frame: Patients will be followed for one year ] [ Designated as safety issue: No ]
|Study Start Date:||April 2004|
|Study Completion Date:||March 2009|
|Primary Completion Date:||March 2009 (Final data collection date for primary outcome measure)|
Drug: Rituximab (Rituxan)
Myasthenia gravis (MG) is an immune-mediated disorder of the neuromuscular junction diagnosed on the basis of clinical, electrophysiological and serological features. Cyclosporine as a disease-modifying therapy has been effective in a controlled study; corticosteroids, immunosuppressive agents such as azathioprine and cyclophosphamide, plasmapheresis and intravenous human immune globulin have shown benefit in uncontrolled trials. There are several drawbacks to currently used medical treatments, including serious and debilitating side-effects, prohibitive costs, and the need for continuous or periodical treatment. Almost 20-25% of patients with MG are unresponsive to commonly used therapies, resulting in significant burden and economic loss. Rituximab is a chimeric anti-CD20 monoclonal antibody which produces a substantial reduction in circulating plasma cells (CD19+) and B cells (CD20+) and provides targeted therapy for B-cell lymphomas. Recently, rituximab has been found to be effective in several antibody-mediated autoimmune processes, including immune thrombocytopenia, autoimmune hemolytic anemia, and IgM-related polyneuropathies. There is preliminary evidence in the literature that treatment of MG patients with rituximab is likely to be of benefit. These observations would strongly suggest that rituximab might benefit refractory MG and needs further study.
|United States, New York|
|State University of New York|
|Syracuse, New York, United States, 13210|
|United States, Vermont|
|University of Vermont Department of Neurology|
|Burlington, Vermont, United States, 05405|
|Principal Investigator:||Rup Tandan, MD, FRCP||University of Vermont Department of Neurology|