Rituximab for Anti-cytokine Autoantibody-Associated Diseases
- Healthy people have white blood cells that protect them against bacteria, viruses, and fungi. However, some people have diseases which cause the body to make white blood cells that do not work properly. These white blood cells can attack the body s own proteins. These types of diseases are called anti-cytokine autoantibody-associated diseases. They can cause severe illnesses and even death. They are also difficult to treat with standard drugs.
- Rituximab is a drug used to treat rheumatoid arthritis. It attacks white blood cells that do not work properly. Currently, it is not approved for treating anti-cytokine autoantibody-associated diseases. However, researchers think that it may be able to help treat people with these immune diseases.
- To see if rituximab is a safe and effective treatment for anti-cytokine autoantibody-associated diseases.
- Individuals at least 18 years of age who have anti-cytokine autoantibody-associated diseases.
- Participants must also be enrolled in a related immune disorder study at the National Institutes of Health.
- The study will last 24 months. Participants will take rituximab for 6 months and have follow-up visits for the remaining 18 months.
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Other samples will be collected as needed if participants currently have an infection.
- Participants will enter the hospital for 1 week at the start of treatment. They will have four doses of rituximab given 2 days apart. This first treatment will be monitored with frequent blood tests.
- Over the next 6 months, participants will have four more doses of rituximab given about 1 month apart. Treatment will be monitored with frequent blood tests and sample collections as needed.
- There will be four follow-up study visits at 3, 6, 12, and 18 months after the last dose of rituximab.
Anticytokine Autoantibody-Associated Diseases
Disseminated Non-Tuberculous Mycobacteria
Chronic Mucocutaneous Candidiasis
Pulmonary Alveolar Proteinosis (PAP)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Rituximab (Anti-CD20) for the Treatment of Subjects With Anticytokine Autoantibody-Associated Diseases|
- The evaluation of adverse events to determine the safety and tolerability of rituximab in subjects with anticytokine autoantibody-associated diseases who are refractory to conventional treatment. [ Time Frame: At the conclusion of the study or if a serious adverse event occurs during the course of the study that may be related to the study drug. ] [ Designated as safety issue: Yes ]
- Evaluation of changes in autoantibody titers in response to rituximab treatment. [ Time Frame: At the conclusion of the study or if a serious adverse event occurs during the course of the study that may be related to the study drug. ] [ Designated as safety issue: No ]
- Assessment of the effects of rituximab on autoantibody-mediatedclinical disease. [ Time Frame: At the conclusion of the study or if a serious adverse event occurs during the course of the study that may be related to the study drug. ] [ Designated as safety issue: Yes ]
- The measurement of both qualitative and quantitative differences in antibody composition and immune function after treatment with rituximab. [ Time Frame: At the conclusion of the study or if a serious adverse event occurs during the course of the study that may be related to the study drug. ] [ Designated as safety issue: Yes ]
|Study Start Date:||February 2013|
|Estimated Study Completion Date:||September 2018|
|Estimated Primary Completion Date:||January 2017 (Final data collection date for primary outcome measure)|
This is a Phase 1, single-arm, open label study.
Rituximab is a genetically engineered chimeric murine/human monoclonal antibody targeting the CD20 antigen expressed on the surface of normal and malignant B cells. It is an FDA-approved drug for the treatment of rheumatoid arthritis and non-Hodgkin's Lymphoma. We have received permission from the FDA to use rituximab for this study.
Anticytokine autoantibodies are an important and emerging cause of disease. Anticytokine autoantibody-associated diseases include disseminated nontuberculous mycobacterial infection caused by anti-interferon- >= autoantibodies, severe mucocutaneous candidiasis caused by anti-interleukin-17 autoantibodies, and pulmonary alveolar proteinosis caused by anti-granulocyte macrophage colony stimulating factor autoantibodies. Many subjects undergoing treatments related to these diseases fail to respond or develop toxicity to long term therapy. Rituximab, an anti-CD20 monoclonal antibody that targets antibody-producing B cells, has been used successfully to treat autoimmune diseases (e.g., rheumatoid arthritis), as well as syndromes caused by pathogenic anticytokine autoantibodies (e.g., myasthenia gravis and pemphigus vulgaris). This is a phase I, single arm, open-label study evaluating the safety and clinical response to rituximab treatment in subjects (greater than or equal to 18 years of age; n=20) with anticytokine autoantibody-associated diseases who are intolerant or refractory to conventional treatment. Rituximab will be administered as intravenous infusions of 1 gram on days 1 and 15, and subsequently if indicated up to once a month for 5 months (plus or minue 5 days for each visit) starting on approximately day 42. Follow-up visits will occur within 3, 6, 9, 12, 15, and 18 months (plus or minus 2 weeks for each visit) after the last infusion. Subjects will be maintained on a background of appropriate therapy for their respective diseases. The safety and clinical response to rituximab will be assessed by clinical and laboratory parameters while subjects are receiving rituximab, and for an additional year and a half after completion of treatment.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01842386
|Contact: Pamela A Welch, R.N.||(301) firstname.lastname@example.org|
|Contact: Christa S Zerbe, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Christa S Zerbe, M.D.||National Institute of Allergy and Infectious Diseases (NIAID)|