A Pilot Trial of Rituxan in Refractory Myasthenia Gravis
Condition: Refractory Myasthenia Gravis
MeSH terms: Myasthenia Gravis; Muscle Weakness
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Rituximab (Rituxan)
Intervention type(s): Drug
Intervention description(s): Four weekly IV infusions of Rituxan with dosage individually calculated per subject.
Other intervention name(s): Rituxan; Rituximab; MabThera
Intervention MeSH terms: Rituximab
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Rituxan; Rituximab; Myasthenia Gravis; MG