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Rituximab Therapy in Refractory Adult and Juvenile Idiopathic Inflammatory Myopathy (IIM)

Phase 2
5 Years
Open (Enrolling)
Myositis, Dermatomyositis, Polymyositis, Juvenile Dermatomyositis

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Trial Information

Rituximab Therapy in Refractory Adult and Juvenile Idiopathic Inflammatory Myopathy (IIM)

Rituximab is a chimeric, murine-human, genetically engineered monoclonal antibody directed
against the CD20 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;; TTY: 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.

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 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:

1. An MMT-8 score that is no greater than 125/150 in conjunction with 2 other abnormal
core set measures.


2. If MMT 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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Outcome Measure:

Comparison between the two groups of IIM patients in their time to achieve improvement

Outcome Time Frame:

Week 44 of treatment phase

Safety Issue:


Principal Investigator

Chester V. Oddis, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Pittsburgh


United States: Food and Drug Administration

Study ID:

N01 AR042273



Start Date:

March 2006

Completion Date:

September 2011

Related Keywords:

  • Myositis
  • Dermatomyositis
  • Polymyositis
  • Juvenile Dermatomyositis
  • rituximab
  • myositis
  • dermatomyositis
  • polymyositis
  • refractory
  • Juvenile Dermatomyositis
  • Dermatomyositis
  • Myositis
  • Polymyositis



University of Alabama Arthritis Intervention Program (Adult Site) Birmingham, Alabama  35294
Phoenix Neurological Associates, LTD (Adult Site) Phoenix, Arizona  85006
Cedars-Sinai Medical Center (Adult Site) Los Angeles, California  90048
Stanford University (Adult Site) Stanford, California  94305
Stanford University (Pediatric Site) Stanford, California  94305
University of Miami School of Medicine (Adult Site) Miami, Florida  33136
Miami Children's Hospital (Pediatric Site) Miami, Florida  33155
University of Kansas Medical Center (Adult Site) Kansas City, Kansas  66160
Kentucky Clinic (Adult Site) Lexington, Kentucky  40536
National Institute of Health (Adult Site) Bethesda, Maryland  20892
National Institute of Health (Pediatric Site) Bethesda, Maryland  20892
Beth Israel Deaconess Medical Center (Adult Site) Boston, Massachusetts  02215
Children's Hospital of Boston (Pediatric Site) Boston, Massachusetts  02115
University of Michigan Health System (Adult Site) Ann Arbor, Michigan  48109
Michigan State University (Adult and Pediatric Site) Grand Rapids, Michigan  49546
Mayo Clinic (Adult Site) Rochester, Minnesota  55905
Mayo Clinic (Pediatric Site) Rochester, Minnesota  55905
North Shore Long Island Jewish Health System (Adult Site) Lake Success, New York  11042
Hospital for Special Surgery (Adult Site) New York, New York  10021
Duke University Medical Center (Pediatric Site) Durham, North Carolina  27710
Cincinnati's Children's Hospital (Pediatric Site) Cincinnati, Ohio  45229
University of Pennsylvania (Adult Site) Philadelphia, Pennsylvania  19104
Children's Hospital of Philadelphia (Pediatric Site) Philadelphia, Pennsylvania  19104
University of Pittsburgh / UPMC (Adult Site) Pittsburgh, Pennsylvania  15261
Children's Hospital of Pittsburgh (Pediatric Site) Pittsburgh, Pennsylvania  15213
University of Texas Southwestern Medical Center (Adult) Dallas, Texas  75390-8884
Medical College of Wisconsin / Froedtert Memorial Luthern Hospital (Adult Site) Milwaukee, Wisconsin  53226