- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00106184
Rituximab for the Treatment of Refractory Adult and Juvenile Dermatomyositis (DM) and Adult Polymyositis (PM)
Rituximab Therapy in Refractory Adult and Juvenile Idiopathic Inflammatory Myopathy (IIM)
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.
Study Overview
Status
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Nova Scotia
-
Halifax, Nova Scotia, Canada, B3K 6R8
- IWK Health Centre
-
-
Ontario
-
Toronto, Ontario, Canada, M5G 1X8
- Hospital for Sick Children (Pediatric Site)
-
-
-
-
-
Prague, Czech Republic
- Institute of Rheumatology
-
-
-
-
-
Stockholm, Sweden
- Karolinska Institute
-
-
-
-
Alabama
-
Birmingham, Alabama, United States, 35294
- University of Alabama Arthritis Intervention Program (Adult Site)
-
-
Arizona
-
Phoenix, Arizona, United States, 85006
- Phoenix Neurological Associates, LTD (Adult Site)
-
-
California
-
Los Angeles, California, United States, 90048
- Cedars-Sinai Medical Center (Adult Site)
-
Stanford, California, United States, 94305
- Stanford University (Adult Site)
-
Stanford, California, United States, 94305
- Stanford University (Pediatric Site)
-
-
Florida
-
Miami, Florida, United States, 33136
- University of Miami School of Medicine (Adult Site)
-
Miami, Florida, United States, 33155
- Miami Children's Hospital (Pediatric Site)
-
-
Kansas
-
Kansas City, Kansas, United States, 66160
- University of Kansas Medical Center (Adult Site)
-
-
Kentucky
-
Lexington, Kentucky, United States, 40536
- Kentucky Clinic (Adult Site)
-
-
Maryland
-
Bethesda, Maryland, United States, 20892
- National Institute of Health (Adult Site)
-
Bethesda, Maryland, United States, 20892
- National Institute of Health (Pediatric Site)
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02115
- Children's Hospital of Boston (Pediatric Site)
-
Boston, Massachusetts, United States, 02215
- Beth Israel Deaconess Medical Center (Adult Site)
-
-
Michigan
-
Ann Arbor, Michigan, United States, 48109
- University of Michigan Health System (Adult Site)
-
Grand Rapids, Michigan, United States, 49546
- Michigan State University (Adult and Pediatric Site)
-
-
Minnesota
-
Rochester, Minnesota, United States, 55905
- Mayo Clinic (Adult Site)
-
Rochester, Minnesota, United States, 55905
- Mayo Clinic (Pediatric Site)
-
-
New York
-
Lake Success, New York, United States, 11042
- North Shore Long Island Jewish Health System (Adult Site)
-
New York, New York, United States, 10021
- Hospital for Special Surgery (Adult Site)
-
-
North Carolina
-
Durham, North Carolina, United States, 27710
- Duke University Medical Center (Pediatric Site)
-
-
Ohio
-
Cincinnati, Ohio, United States, 45229
- Cincinnati's Children's Hospital (Pediatric Site)
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19104
- Children's Hospital of Philadelphia (Pediatric Site)
-
Philadelphia, Pennsylvania, United States, 19104
- University of Pennsylvania (Adult Site)
-
Pittsburgh, Pennsylvania, United States, 15213
- Children's Hospital of Pittsburgh (Pediatric Site)
-
Pittsburgh, Pennsylvania, United States, 15261
- University of Pittsburgh / UPMC (Adult Site)
-
-
Texas
-
Dallas, Texas, United States, 75390-8884
- University of Texas Southwestern Medical Center (Adult)
-
-
Wisconsin
-
Milwaukee, Wisconsin, United States, 53226
- Medical College of Wisconsin / Froedtert Memorial Luthern Hospital (Adult Site)
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Adults with definite or probable dermatomyositis or polymyositis and pediatric patients five years of age and over with definite or probable juvenile dermatomyositis (JDM) by Bohan and Peter criteria. Diagnosis of JDM based on an age of onset (i.e., first symptom of myositis or dermatomyositis rash) is less 18 years of age
- Refractory myositis, defined by intolerance to or inadequate response to corticosteroids plus an adequate regime of at least one other immunosuppressive agent. Intolerance is defined as side effects that require discontinuation of the medication or an underlying condition that precludes further use of the medication.
- Baseline manual muscle testing which is based on a maximum MMT-8 (Manual Muscle Test) score of 150:Adult subjects with dermatomyositis (DM) or polymyositis (PM) must have a score that is no greater than 125/150 in conjunction with 2 other abnormal core set measures.
Subjects with a diagnosis of Juvenile Dermatomyositis (JDM) must meet either of the following criteria:
An MMT-8 (Manual Muscle Test) score that is no greater than 125/150 in conjunction with 2 other abnormal core set measures.
OR
If MMT (Manual Muscle Test) score is greater than 125/150 the patient MUST meet at least 3 abnormal core set measures.
- Background therapy with at least 1 non-corticosteroid immunosuppressive agent at a stable dose for at least 6 weeks prior to screening
- Able and willing to complete self-report questionnaires. Parents of pediatric participants will be required to complete the questionnaires on behalf of their children.
- Willing to use acceptable forms of contraception for the duration of the study for patients of reproductive potential.
- Parent willing to provide informed consent, if applicable
- Willing to forgo immunization with a live vaccine for the duration of the study
Exclusion Criteria:
- Drug-induced myositis. Patients who have myositis or myopathic syndromes caused by taking medications known to induce myositis-like syndromes, including but not limited to statin agents, fibric acid derivatives, colchicine, and hydroxychloroquine.
- Juvenile polymyositis
- Inclusion body myositis
- Cancer-associated myositis, defined as the diagnosis of myositis within 2 years of the diagnosis of cancer. Patients with basal or squamous cell skin cancer or carcinoma in situ of the cervix are not excluded, if it has been at least 5 years since excision.
- Myositis in overlap with another connective tissue disease that may preclude the accurate assessment of a treatment response
- Live viral vaccine within 4 weeks prior to study entry
- Any joint disease or other musculoskeletal condition that may interfere with muscle strength testing
- Known hypersensitivity to mouse proteins
- Any concomitant or life-threatening non-myositis illness that, in the opinion of the investigator, may interfere with the study
- Known or suspected history of drug or alcohol abuse within the last 6 months prior to study entry, as determined by medical record or patient interview
- Anticipated poor compliance with study requirements
- Participation in another clinical trial within 30 days prior to screening
- Any history or evidence of any severe illness or other condition that, in the opinion of the investigator, may interfere with the study
- Previously received rituximab
- Evidence of prior infection with hepatitis B or hepatitis C virus
- Initiation of an exercise program within 4 weeks of screening OR initiation of an exercise program during the study
- Consumed any creatine-containing, over-the-counter products in the form of dietary supplements 30 days prior to screening visit and for the duration of the study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Adult Study Group 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)
|
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
Other Names:
Treatment Group A: placebo infusion at Weeks 8 and 9 Treatment Group B: placebo infusion at Weeks 0 and 1 |
Experimental: Adult Study Group 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)
|
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
Other Names:
Treatment Group A: placebo infusion at Weeks 8 and 9 Treatment Group B: placebo infusion at Weeks 0 and 1 |
Experimental: Adult Study Group 3
Adult dermatomyositis patients who will receive rituximab at Weeks 0 and 1 followed by placebo at Weeks 8 and 9 (Treatment Group A)
|
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
Other Names:
Treatment Group A: placebo infusion at Weeks 8 and 9 Treatment Group B: placebo infusion at Weeks 0 and 1 |
Experimental: Adult Study Group 4
Adult dermatomyositis patients who will receive placebo at Weeks 0 and 1 followed by rituximab at Weeks 8 and 9 (Treatment Group B)
|
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
Other Names:
Treatment Group A: placebo infusion at Weeks 8 and 9 Treatment Group B: placebo infusion at Weeks 0 and 1 |
Experimental: JDM Study Group 1
Refractory juvenile dermatomyositis patients who will receive rituximab at Weeks 0 and 1 followed by placebo at Weeks 8 and 9 (Treatment Group A)
|
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
Other Names:
Treatment Group A: placebo infusion at Weeks 8 and 9 Treatment Group B: placebo infusion at Weeks 0 and 1 |
Experimental: JDM Study Group 2
Refractory juvenile dermatomyositis patients who will receive placebo at Weeks 0 and 1 followed by rituximab at Weeks 8 and 9 (Treatment Group B)
|
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
Other Names:
Treatment Group A: placebo infusion at Weeks 8 and 9 Treatment Group B: placebo infusion at Weeks 0 and 1 |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Comparison Between the Time to Improvement Between the Two Groups of IIM (Idiopathic Inflammatory Myopathy) Patients
Time Frame: Week 44 of treatment phase
|
The Definition of Improvement for both adult and pediatric patients will be: 3 of any of the 6 core set measures improved by ≥ 20%, with no more than 2 of the core set measures worsening by ≥25% (worsening measure cannot include the MMT) at two consecutive visits. Of note, the MMT could not be one of the worsening measures. Core Set Measures Included:
|
Week 44 of treatment phase
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Response Rates (Proportion of Improved Patients) Between Groups A (Rituximab Wks 0 and 1) and B (Rituximab Wks 8 and 9) at Week 8
Time Frame: Week 8 of the treatment phase
|
The Definition of Improvement for both adult and pediatric patients will be: 3 of any of the 6 core set measures improved by ≥ 20%, with no more than 2 of the core set measures worsening by ≥25% (worsening measure cannot include the MMT) at two consecutive visits. Of note, the MMT could not be one of the worsening measures. Core Set Measures Included:
|
Week 8 of the treatment phase
|
20% Improvement in Manual Muscle Testing (MMT) Over Baseline on Two Consecutive Time Points (Muscle is the Primary Organ of Involvement, and MMT is the One Objective Measurement of the Definition of Improvement [DOI])
Time Frame: Week 44 of treatment phase
|
Number of participants with a 20% improvement in MMT over baseline on two consecutive time points.
|
Week 44 of treatment phase
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Chester V. Oddis, MD, University of Pittsburgh
- Principal Investigator: Ann M. Reed, MD, Mayo Clinic
Publications and helpful links
General Publications
- Feldman B, Wang E, Willan A, Szalai JP. The randomized placebo-phase design for clinical trials. J Clin Epidemiol. 2001 Jun;54(6):550-7. doi: 10.1016/s0895-4356(00)00357-7.
- Levine TD. Rituximab in the treatment of dermatomyositis: an open-label pilot study. Arthritis Rheum. 2005 Feb;52(2):601-7. doi: 10.1002/art.20849.
- Oddis CV, Reed AM, Aggarwal R, Rider LG, Ascherman DP, Levesque MC, Barohn RJ, Feldman BM, Harris-Love MO, Koontz DC, Fertig N, Kelley SS, Pryber SL, Miller FW, Rockette HE; RIM Study Group. Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial. Arthritis Rheum. 2013 Feb;65(2):314-24. doi: 10.1002/art.37754.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Nervous System Diseases
- Skin Diseases
- Musculoskeletal Diseases
- Connective Tissue Diseases
- Muscular Diseases
- Neuromuscular Diseases
- Myositis
- Dermatomyositis
- Polymyositis
- Physiological Effects of Drugs
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Rituximab
Other Study ID Numbers
- N01 AR042273
- 5R01AR061298-02 (U.S. NIH Grant/Contract)
- HHSN26420042273C
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Myositis
-
Novartis PharmaceuticalsCompletedSporadic Inclusion Body Myositis (sIBM)United States
-
University of Kansas Medical CenterCompletedInclusion Body Myositis | Sporadic Inclusion Body MyositisUnited States
-
Novartis PharmaceuticalsCompletedSporadic Inclusion Body MyositisUnited States
-
Institut National de la Santé Et de la Recherche...CompletedInclusion Body Myositis (IBM)France
-
La-ser Europe LimitedUnknownSporadic Inclusion Body Myositis
-
Assistance Publique - Hôpitaux de ParisRecruitingInflammatory Myositis | Idiopathic Inflammatory Myositis | Drug-induced Inflammatory MyositisFrance
-
University of Southern DenmarkOdense University HospitalCompleted
-
University of Kansas Medical CenterBioSensicsRecruitingInclusion Body MyositisUnited States
-
Abcuro, Inc.Active, not recruitingInclusion Body MyositisAustralia
-
ZevraDenmarkUniversity College, London; University of Kansas Medical CenterTerminatedInclusion Body MyositisUnited States, United Kingdom
Clinical Trials on Rituximab
-
Children's Oncology GroupNational Cancer Institute (NCI)Active, not recruitingEBV-Related Post-Transplant Lymphoproliferative Disorder | Monomorphic Post-Transplant Lymphoproliferative Disorder | Polymorphic Post-Transplant Lymphoproliferative Disorder | Recurrent Monomorphic Post-Transplant Lymphoproliferative Disorder | Recurrent Polymorphic Post-Transplant Lymphoproliferative... and other conditionsUnited States
-
Academic and Community Cancer Research UnitedNational Cancer Institute (NCI)Active, not recruitingRecurrent Grade 1 Follicular Lymphoma | Recurrent Grade 2 Follicular Lymphoma | Recurrent Mantle Cell Lymphoma | Recurrent Marginal Zone Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Recurrent Small Lymphocytic Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma | Recurrent Grade 3a Follicular... and other conditionsUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)RecruitingAnn Arbor Stage I Grade 1 Follicular Lymphoma | Ann Arbor Stage I Grade 2 Follicular Lymphoma | Ann Arbor Stage II Grade 1 Follicular Lymphoma | Ann Arbor Stage II Grade 2 Follicular LymphomaUnited States
-
National Cancer Institute (NCI)CompletedAnn Arbor Stage III Grade 1 Follicular Lymphoma | Ann Arbor Stage III Grade 2 Follicular Lymphoma | Ann Arbor Stage IV Grade 1 Follicular Lymphoma | Ann Arbor Stage IV Grade 2 Follicular Lymphoma | Ann Arbor Stage II Grade 3 Contiguous Follicular Lymphoma | Ann Arbor Stage II Grade 3 Non-Contiguous... and other conditionsUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingRecurrent Small Lymphocytic Lymphoma | Prolymphocytic Leukemia | Recurrent Chronic Lymphocytic LeukemiaUnited States
-
National Cancer Institute (NCI)Celgene CorporationActive, not recruitingAnn Arbor Stage III Grade 1 Follicular Lymphoma | Ann Arbor Stage III Grade 2 Follicular Lymphoma | Ann Arbor Stage IV Grade 1 Follicular Lymphoma | Ann Arbor Stage IV Grade 2 Follicular Lymphoma | Ann Arbor Stage II Grade 3 Contiguous Follicular Lymphoma | Ann Arbor Stage II Grade 3 Non-Contiguous... and other conditionsUnited States
-
PfizerCompletedRheumatoid ArthritisUnited States, Australia, Canada, Israel, Mexico, Colombia, Germany, Russian Federation, South Africa, United Kingdom
-
Mabion SAParexelWithdrawn
-
National Cancer Institute (NCI)Active, not recruitingRecurrent Mantle Cell Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma | Refractory Mantle Cell LymphomaUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)RecruitingChronic Lymphocytic Leukemia/Small Lymphocytic LymphomaUnited States