Clinical trial NCT00106184
Conditions: Myositis Dermatomyositis Polymyositis Juvenile Dermatomyositis
Keywords: rituximab myositis dermatomyositis polymyositis refractory Juvenile Dermatomyositis
Sponsor: University of Pittsburgh
Start date: 2006-03-01; Completion date: 2010-08-01
Enrollment: 200 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Rituximab is a man-made antibody used to treat certain types of cancer. This study will determine whether rituximab is an effective treatment for adult and pediatric patients with dermatomyositis or polymyositis.

Study hypotheses: 1) The time to improvement in Group A patients (receiving rituximab first) will occur significantly earlier than in Group B patients (receiving rituximab later). 2) The proportion of patients improved at Week 8 of the treatment phase will be significantly greater in Group A than in Group B.

Detailed description:
Rituximab is a chimeric, murine-human, genetically engineered monoclonal antibody directed against the CD20 (cluster of differentiation antigen 20) antigen found on the surface of B-lymphocytes and is known to deplete B cells when administered intravenously. It is approved to treat non-Hodgkin's lymphoma. Rituximab has been used for autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and immune-mediated hematologic disorders. It has also been studied and used in small numbers of patients with myositis. This study will evaluate the efficacy of rituximab in treating refractory adult and pediatric patients with dermatomyositis and adult polymyositis.

A patient's participation in this study will last approximately 45 weeks. At screening, participants will have a physical exam, muscle strength assessment, an electrocardiogram, and blood and urine collection; they will also be asked to complete several questionnaires. All participants will receive 2 infusions of rituximab and 2 infusions of placebo. Participants will be randomly assigned to one of two groups. Group A will receive rituximab at Weeks 0 and 1 and placebo at Weeks 8 and 9. Group B will receive placebo at Weeks 0 and 1 and rituximab at Weeks 8 and 9. Each infusion will be given on an outpatient basis over a minimum of approximately 5 hours' time.

There will be a total of 14 study visits. All participants will visit the outpatient clinic at selected time points for muscle strength testing, a physical exam, disease activity measurements, and blood collection. During the study, participants will be monitored closely for improvement or worsening of their disease and for serious drug related side effects. Some participants will be asked if they are willing to undergo 2 muscle biopsy procedures, 1 prior to receiving study medication and 1 after receiving study medication, to determine the effects of rituximab on muscle tissue.

If a participant is unable to locate a near-by clinical center, the adult and pediatric centers at the National Institute of Health located in Bethesda, Maryland have funds available to assist with travel costs.

NIH SUB-STUDY: "Rituximab to Treat Dermatomyositis and Polymyositis"

* This study is currently recruiting patients.
* Sponsored by: National Institute of Environmental Health Sciences (NIEHS)
* Information provided by: National Institutes of Health Clinical Center (CC)
* Expected Total Enrollment: 30
* Study start: October 2006
* Location and Contact Information: Patient Recruitment and Public Liaison Office;(800) 411-1222; prpl@mail.cc.nih.gov; Phone: 1-866-411-1010

The NIH sub-study will take advantage of the multi-center core RIM trial to identify changes in gene expression patterns in muscle, skin, and peripheral blood and the imaging features and immunopathology of muscle, skin, and peripheral cells before (week 0) and after (week 16) therapy. These changes will also be correlated with the large number of clinical, laboratory, and research variables already planned to be collected in the core RIM Study. Furthermore, knowing specifically which gene expression patterns are altered in resistant patients before rituximab, and which are changed after rituximab therapy - in conjunction with flow cytometry of peripheral cells and immunopathology of the tissues - will help in understanding more about the pathogenesis of myositis and the possible contribution of B lymphocytes and their subsets.

Patients with dermatomyositis and polymyositis who meet the inclusion/exclusion criteria for the core RIM trial may be eligible for this sub-study. The following procedures will be conducted in addition to the core RIM trial procedures during the 13 clinic visits over a period of 44 weeks:

* Weeks 0, 16: Muscle and skin biopsy (adult only). Small samples of muscle and skin tissue will be surgically removed for examination under a microscope.
* Weeks 0, 8, 16, 44: Skin evaluation and photography. The effect of the disease on the skin will be thoroughly evaluated and photographs of any rashes and of the skin around the nails will be taken.
* Weeks 0, 8, 16, 44: Magnetic resonance imaging (MRI). All participants will have MRI scans of the skin and of the muscle in the legs. Adults will also have an MRI to examine blood flow in the muscle.

Arms: arm 1: Refractory adult polymyositis patients who will receive rituximab at Weeks 0 and 1 followed by placebo at Weeks 8 and 9 (Treatment Group A) arm 2: Refractory adult polymyositis patients who will receive placebo at Weeks 0 and 1 followed by rituximab at Weeks 8 and 9 (Treatment Group B) arm 3: Adult dermatomyositis patients who will receive rituximab at Weeks 0 and 1 followed by placebo at Weeks 8 and 9 (Treatment Group A) arm 4: Adult dermatomyositis patients who will receive placebo at Weeks 0 and 1 followed by rituximab at Weeks 8 and 9 (Treatment Group B) arm 5: Refractory juvenile dermatomyositis patients who will receive rituximab at Weeks 0 and 1 followed by placebo at Weeks 8 and 9 (Treatment Group A) arm 6: Refractory juvenile dermatomyositis patients who will receive placebo at Weeks 0 and 1 followed by rituximab at Weeks 8 and 9 (Treatment Group B)
Interventions: intervention 1: Rituximab intervention 2: Placebo
Intervention descriptions: intervention 1: Treatment Group A - intravenous rituximab 750mg/m2 BSA (Body Surface Area) up to a maximum dose of 1 gram at Weeks 0 and 1 Group B - intravenous rituximab 750mg/m2 BSA (Body Surface Area) up to a maximum does of 1 gram at Weeks 8 and 9 intervention 2: Treatment Group A: placebo infusion at Weeks 8 and 9

Treatment Group B: placebo infusion at Weeks 0 and 1

Protocol documents: