Refractory Myasthenia Gravis Clinical Trial
Official title:
Phase 1-2 Pilot Study of Rituximab (Rituxan) in Refractory Myasthenia Gravis.
Verified date | January 2013 |
Source | University of Vermont |
Contact | n/a |
Is FDA regulated | No |
Health authority | United States: Food and Drug Administration |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 10 |
Est. completion date | March 2009 |
Est. primary completion date | March 2009 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years to 80 Years |
Eligibility |
Inclusion Criteria: Criteria for patient selection will be based upon the recent recommendations for clinical research standards by the Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America (Jaretzki et al, 2000). Patients will be included in the trial based upon fulfilling all the criteria given below, except that they will be required to fulfill criterion 3 OR 4: 1. Patients must have a diagnosis of "Definite" MG (Seybold, 1999) as based on clinical, electrophysiological and serological criteria (Appendix 1) 2. Patients must have disease predominantly affecting bulbar or respiratory muscles of moderate or severe degree (Osserman grades 2B, 3 without crisis, or 4 without crisis) (Osserman and Genkins, 1971 and Appendix 2) as listed in Appendix 3, and a Quantitative MG score of <25 (Appendix 7) 3. Patients must have disease refractory to treatment for at least 12 months with prednisone at a dose of 15mg/day and/or immunosuppressive drugs (azathioprine or cyclophosphamide at a dose of 100mg/day or cyclosporine at a dose to produce trough levels of >50), with or without thymectomy and plasmapheresis/IVIG alone or in combination with above drugs at intervals of no more than once every 3 weeks, OR 4. Patients must have experienced intolerance or unacceptable side-effects following treatment with corticosteroids, immunosuppressive drugs (azathioprine, cyclophosphamide or cyclosporine), plasmapheresis or IVIG 5. Patients must be between 18 years and 80 years old 6. Patients must have adequate organ function / laboratory parameters as measured by the following criteria (values should be obtained within 2 weeks prior to enrollment): - Documented CD20 + cells - Absolute neutrophil count: >2000/mm3 - Platelets: >100,000/mm3 - Hemoglobin: >10 gm/dL - Adequate renal function as indicated by normal BUN and creatinine levels - Adequate liver function, as indicated by AST and ALT <2x Upper Limit of normal. - Normal serum electrolytes 7. Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for one year after completion of treatment 8. Written informed consent. Exclusion Criteria: Patients will be excluded from the trial based on the following criteria: 1. Myasthenic crisis with a forced vital capacity (FVC) of <30% predicted, irrespective of need for respiratory support, or severe bulbar involvement (Appendix 3) 2. Patients requiring maintenance plasmapheresis or IVIG infusions at intervals of less than once every three weeks 3. Patients requiring respiratory support with invasive or non-invasive ventilation 4. Severe, uncontrolled or untreated concomitant cardiac (New York Heart Classification III or IV disease), hepatic, pulmonary, renal, hematologic or psychiatric disease 5. Toxicity grade 2 or more prior to treatment with rituximab in patients who failed prior treatments 6. Patients unwilling to attend for follow-up visits according to the study design 7. Patients will be excluded based on the following criteria: - History of HIV disease - Active Hepatitis B infection - Pregnancy (a serum pregnancy test will be performed for all women of childbearing potential immediately before treatment) - Active infection 8. Pregnant or breastfeeding women may not participate due to the lack of information on effects of rituximab on the fetus and developing child 9. Concomitant malignancies or previous malignancies within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix. 10. No prior monoclonal antibody therapy. 11. History of significant psychiatric disease that will interfere with the consenting procedure, research visits, treatment protocol or evaluation of patients in the study. |
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
United States | University of Vermont Department of Neurology | Burlington | Vermont |
United States | State University of New York | Syracuse | New York |
Lead Sponsor | Collaborator |
---|---|
University of Vermont | Genentech, Inc. |
United States,
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* Note: There are 28 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | To examine the effects of rituximab on disease activity in MG patients with refractory disease. | Patients will be followed for one year | No | |
Secondary | To determine the safety and tolerability of rituximab in MG patients with refractory disease. | Patients will be followed for one year | No |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05332587 -
Efficacy and Safety of Low-dose Rituximab in the Treatment of Refractory Myasthenia Gravis
|
Phase 3 |