Stem Cell Transplantation in Idiopathic Inflammatory Myopathy Diseases

NCT00278564 | Terminated Phase 1 Results

• 1 other identifier: NU FDA IIM.Auto2003
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Myositis is a disease, believed to be due to immune cells, cells which normally protect the body, but are now attacking the muscles and other organ systems within body. As a result, the affected muscles and organs fail to work properly causing weakness, difficulty swallowing, skin rash, respiratory problems, heart problems, joint stiffness, soft tissue calcification and vasculitis (blood circulation problems). The likelihood of progression of this disease is high. This study is designed to examine whether treating patients with high dose cyclophosphamide (a drug which reduces the function of the immune system) and ATG (a protein that kills the immune cells that are thought to be causing this disease), followed by return of previously collected blood stem cells will stop the progression of myositis.

Conditions

MYOPATHY

Outcome Measures

Primary Outcomes (1)

• Survival

  Survival

  up to 5 years

Study Arms (1)

Hematopoietic stem cell transplantation

EXPERIMENTAL

Intervention as hematopoietic stem cells transplantation after conditioning regimen: Autologous hematopoietic stem cells will be injected after conditioning regimen

Biological: Hematopoietic stem cell transplantation; Drug: Cyclophosphamide; Drug: Mesna; Drug: ATG(rabbit); Drug: Methylprednisolone; Drug: G-CSF; Drug: Rituxan

Interventions

Mesna DRUG

Hematopoietic stem cell transplantation

ATG(rabbit) DRUG

Hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation BIOLOGICAL

Autologous hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation

Cyclophosphamide DRUG

Also known as: Cytoxan

Hematopoietic stem cell transplantation

Methylprednisolone DRUG

Hematopoietic stem cell transplantation

G-CSF DRUG

Hematopoietic stem cell transplantation

Rituxan DRUG

Hematopoietic stem cell transplantation

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 16 years and ≤ 65 years at the time of pretransplant evaluation.
• An established diagnosis of polymyositis, dermatomyositis, juvenile polymyositis/dermatomyositis, and myositis associated with other collagen diseases. Diagnosis requires electrophysiological studies and histopathologic features. MRI evidence of muscle inflammation or histological evidence of active myositis is mandatory at entry. If patient had dermatomyositis/polymyositis associated with malignancy, the patient has to be free of malignancy for 5 years and considered to be cured.
• Patients who failed conventional treatment of at least 3 months duration including high-dose corticosteroids (equivalent dosage of prednisone \>1.0 mg/kg/day to start), and must also have failed two or more of the followings: cyclophosphamide, azathioprine, 6-MP, methotrexate, tacrolimus, cyclosporin A, mycophenolate mofetil, TNF inhibitor (e.g. etanercept), IVIG or any other immunosuppressive drugs or immune modulating drugs.
• Failure is defined by (one or more of the following) (not caused by unrelated conditions):
• Persistent muscle weakness (grade 4/5 or worse by MRC) with elevation of muscle derived enzymes (CPK, aldolase)
• Worsening pulmonary function especially %VC or DLCo \> 15% over 12 months indicating active alveolitis.
• Abnormal EKG or echocardiographic evidence of cardiomyopathy.
• Presence of progressive joint contracture, progressive calcinosis, vasculitis, or skin ulcers in juvenile dermatomyositis/polymyositis.

You may not qualify if:

• Poor performance (PS) status (ECOG \>2) at the time of entry, unless decline of PS is due to the disease itself.
• Significant end organ damage such as (not caused by IIM):
• LVEF \<40% or deterioration of LVEF during exercise test on MUGA or echocardiogram.
• Untreated life-threatening arrhythmia.
• Active ischemic heart disease or heart failure.
• DLCo \<40% or FEV1/FEV \< 50%.
• Serum creatinine \>2.5 or creatinine clearance \<30ml/min.
• Liver cirrhosis, transaminases \>3x of normal limits or bilirubin \>2.0 unless due to Gilbert disease.
• HIV positive.
• Uncontrolled diabetes mellitus, or any other illness that in the opinion of the investigators would jeopardize the ability of the patient to tolerate aggressive treatment.
• Prior history of malignancy except localized basal cell or squamous skin cancer. Other malignancies for which the patient is judged to be cured by local surgical therapy, such as (but not limited to) head and neck cancer, or stage I or II breast cancer will be considered on an individual basis.
• Positive pregnancy test, inability or unable to pursue effective means of birth control, failure to willingly accept or comprehend irreversible sterility as a side effect of therapy.
• Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible.
• Inability to give informed consent.
• Major hematological abnormalities such as platelet count less than 100,000/ul, ANC less than 1000/ul.

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (1)

Northwestern University, Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Muscular Diseases

Interventions

Hematopoietic Stem Cell Transplantation; Cyclophosphamide; Mesna; thymoglobulin; Methylprednisolone; Granulocyte Colony-Stimulating Factor; Rituximab

Condition Hierarchy (Ancestors)

Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed

Results Point of Contact

• Title: Dr. Richard Burt
• Organization: Northwestern University

rburt@northwestern.edu

312-695-4960

Study Officials

• Richard Burt, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 15, 2006
• First Posted: January 18, 2006
• Study Start: September 1, 2005
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: August 6, 2018
• Results First Posted: August 6, 2018

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)