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

Rituximab for the Treatment of Refractory Adult and Juvenile Dermatomyositis (DM) and Adult Polymyositis (PM)



Sponsors


Source

University of Pittsburgh

Oversight Info

Has Dmc

Yes


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.

Overall Status

Completed

Start Date

2006-03-01

Completion Date

2010-08-01

Primary Completion Date

2010-02-01

Phase

Phase 2

Study Type

Interventional

Primary Outcome

Measure

Time Frame

Comparison Between the Time to Improvement Between the Two Groups of IIM (Idiopathic Inflammatory Myopathy) Patients
Week 44 of treatment phase

Secondary Outcome

Measure

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
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])
Week 44 of treatment phase

Enrollment

200

Conditions


Intervention

Intervention Type

Drug

Intervention Name


Description

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

Arm Group Label

Adult Study Group 1

Adult Study Group 2

Adult Study Group 3

Adult Study Group 4

JDM Study Group 1

JDM Study Group 2


Other Name

Rituxan


Intervention Type

Drug

Intervention Name


Description

Treatment Group A: placebo infusion at Weeks 8 and 9
Treatment Group B: placebo infusion at Weeks 0 and 1

Arm Group Label

Adult Study Group 1

Adult Study Group 2

Adult Study Group 3

Adult Study Group 4

JDM Study Group 1

JDM Study Group 2




Eligibility

Criteria

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:

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

OR

2. 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

Gender

All

Minimum Age

5 Years

Maximum Age

N/A

Healthy Volunteers

No


Overall Official

Last Name

Role

Affiliation

Chester V. Oddis, MD
Principal Investigator
University of Pittsburgh
Ann M. Reed, MD
Principal Investigator
Mayo Clinic

Location

Facility

University of Alabama Arthritis Intervention Program (Adult Site)
Birmingham Alabama 35294 United States
Phoenix Neurological Associates, LTD (Adult Site)
Phoenix Arizona 85006 United States
Cedars-Sinai Medical Center (Adult Site)
Los Angeles California 90048 United States
Stanford University (Adult Site)
Stanford California 94305 United States
Stanford University (Pediatric Site)
Stanford California 94305 United States
University of Miami School of Medicine (Adult Site)
Miami Florida 33136 United States
Miami Children's Hospital (Pediatric Site)
Miami Florida 33155 United States
University of Kansas Medical Center (Adult Site)
Kansas City Kansas 66160 United States
Kentucky Clinic (Adult Site)
Lexington Kentucky 40536 United States
National Institute of Health (Adult Site)
Bethesda Maryland 20892 United States
National Institute of Health (Pediatric Site)
Bethesda Maryland 20892 United States
Children's Hospital of Boston (Pediatric Site)
Boston Massachusetts 02115 United States
Beth Israel Deaconess Medical Center (Adult Site)
Boston Massachusetts 02215 United States
University of Michigan Health System (Adult Site)
Ann Arbor Michigan 48109 United States
Michigan State University (Adult and Pediatric Site)
Grand Rapids Michigan 49546 United States
Mayo Clinic (Adult Site)
Rochester Minnesota 55905 United States
Mayo Clinic (Pediatric Site)
Rochester Minnesota 55905 United States
North Shore Long Island Jewish Health System (Adult Site)
Lake Success New York 11042 United States
Hospital for Special Surgery (Adult Site)
New York New York 10021 United States
Duke University Medical Center (Pediatric Site)
Durham North Carolina 27710 United States
Cincinnati's Children's Hospital (Pediatric Site)
Cincinnati Ohio 45229 United States
Children's Hospital of Philadelphia (Pediatric Site)
Philadelphia Pennsylvania 19104 United States
University of Pennsylvania (Adult Site)
Philadelphia Pennsylvania 19104 United States
Children's Hospital of Pittsburgh (Pediatric Site)
Pittsburgh Pennsylvania 15213 United States
University of Pittsburgh / UPMC (Adult Site)
Pittsburgh Pennsylvania 15261 United States
University of Texas Southwestern Medical Center (Adult)
Dallas Texas 75390-8884 United States
Medical College of Wisconsin / Froedtert Memorial Luthern Hospital (Adult Site)
Milwaukee Wisconsin 53226 United States
IWK Health Centre
Halifax Nova Scotia B3K 6R8 Canada
Hospital for Sick Children (Pediatric Site)
Toronto Ontario M5G 1X8 Canada
Institute of Rheumatology
Prague Czech Republic
Karolinska Institute
Stockholm Sweden

Location Countries

Country

Canada

Czech Republic

Sweden

United States



Verification Date

2015-03-01

Lastchanged Date

N/A

Firstreceived Date

N/A

Responsible Party

Responsible Party Type

Principal Investigator

Investigator Affiliation

University of Pittsburgh

Investigator Full Name

Chester Oddis

Investigator Title

MD, Professor of Medicine, University of Pittsburgh, Division of Rheumatology and Clinical Immunology


Keywords


Has Expanded Access

No

Condition Browse


Secondary Id

5R01AR061298-02

HHSN26420042273C


Number Of Arms

6

Intervention Browse

Mesh Term

Rituximab


Arm Group

Arm Group Label

Adult Study Group 1

Arm Group Type

Experimental

Description

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 Group Label

Adult Study Group 2

Arm Group Type

Experimental

Description

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 Group Label

Adult Study Group 3

Arm Group Type

Experimental

Description

Adult dermatomyositis patients who will receive rituximab at Weeks 0 and 1 followed by placebo at Weeks 8 and 9 (Treatment Group A)


Arm Group Label

Adult Study Group 4

Arm Group Type

Experimental

Description

Adult dermatomyositis patients who will receive placebo at Weeks 0 and 1 followed by rituximab at Weeks 8 and 9 (Treatment Group B)


Arm Group Label

JDM Study Group 1

Arm Group Type

Experimental

Description

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 Group Label

JDM Study Group 2

Arm Group Type

Experimental

Description

Refractory juvenile dermatomyositis patients who will receive placebo at Weeks 0 and 1 followed by rituximab at Weeks 8 and 9 (Treatment Group B)



Results Reference

Citation

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.

PMID

23124935


Firstreceived Results Date

N/A

Reference

Citation

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.

PMID

11377114


Citation

Levine TD. Rituximab in the treatment of dermatomyositis: an open-label pilot study. Arthritis Rheum. 2005 Feb;52(2):601-7.

PMID

15692974



Removed Countries

Country

United Kingdom


Nct Alias

NCT00393237

Firstreceived Results Disposition Date

N/A

Study Design Info

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary Purpose

Treatment

Masking

Triple (Participant, Care Provider, Investigator)


Study First Submitted

March 21, 2005

Study First Submitted Qc

March 21, 2005

Study First Posted

March 22, 2005

Last Update Submitted

March 3, 2015

Last Update Submitted Qc

March 3, 2015

Last Update Posted

March 4, 2015

Results First Submitted

October 10, 2013

Results First Submitted Qc

March 3, 2015

Results First Posted

March 4, 2015


ClinicalTrials.gov processed this data on August 24, 2018

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.



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