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Stem Cell Transplantation in Idiopathic Inflammatory Myopathy Diseases

This study has been terminated.
(high relapse rate)
Sponsor:
ClinicalTrials.gov Identifier:
NCT00278564
First Posted: January 18, 2006
Last Update Posted: July 15, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Richard Burt, MD, Northwestern University
January 15, 2006
January 18, 2006
July 15, 2016
September 2005
July 2016   (Final data collection date for primary outcome measure)
Toxicity;Survival;Disease improvement defined by muscle strength (one or more in MRC scale) and improvement of muscle derived enzymes (normalization) or improvement of pulmonary function tests [ Time Frame: 5 years after transplant ]
  • 1 Toxicity
  • 2 Survival
  • 3 Disease improvement defined by muscle strength (one or more in MRC scale) and improvement of muscle derived enzymes (normalization) or improvement of pulmonary function tests.
  • 4 Time to disease progression defined by worsening muscle strength (one or more in MRC scale) or worsening of pulmonary function tests.
Complete list of historical versions of study NCT00278564 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Stem Cell Transplantation in Idiopathic Inflammatory Myopathy Diseases
High Dose Cyclophosphamide & ATG With Hematopoietic Stem Cell Transplantation in Patients With Refractory Idiopathic Inflammatory Myopathy Diseases: A Phase I Trial
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.

Conditioning Regimen (In order to assure sterility testing, a minimum of 14 days will be required between stem cell collection and starting the conditioning regimen).

The conditioning regimen is outlined in below:

Cyclophosphamide 50 mg/kg/day will be given IV over 1 hour in 250 cc of normal saline on day -5, -4, -3, and -2. If actual weight is < ideal weight, cyclophosphamide will be given based on actual weight. If actual weight is > ideal weight, cyclophosphamide will be given as adjusted ideal weight. Adjusted ideal weight = ideal weight + 40% (actual weight minus ideal weight).

Mesna 50mg/kg/day will be given IV over 24 hours in 250 cc of normal saline or D5W starting at 10AM each dose. Weight base is calculated same as cyclophosphamide as above.

1ATG (rabbit) 0.5 mg/kg on day -6 and 1mg/kg on day -5, -4, -3, -2 and -1 (total 5.5mg/kg, no dose adjustment) will be given IV over 10 hours in 250 cc of normal saline beginning at least 1 hour after infusion of cyclophosphamide. Premedicate with acetaminophen 650 mg po and diphenhydramine 25 mg po/IV 30 minutes before the infusion.

Methylprednisolone A suggested dose of 250mg IV should be administered 30 minutes before each ATG infusion.

Hydration A suggested rate of 125 cc/hr NS should be given starting 6 hours before the first cyclophosphamide dose and continued until 24 hours after the last cyclophosphamide dose. The rate of hydration will be aggressively adjusted. BID weights will be obtained. Amount of fluid can be modified based on patient's fluid status. Minimum target urine output is 2 liters/m2/day

G-CSF 5 mcg/kg/day will be given subcutaneously and continued until the absolute neutrophil counts reaches at least 500/µl.

Rituxan 500 mg will be given IV on the day before the first dose of ATG and the day after stem cell infusion.

Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
MYOPATHY
Biological: hematopoietic stem cell transplantation
Autologous hematopoietic stem cell transplantation
Experimental: Hematopoietic stem cell transplantation
Autologous hematopoietic stem cells will be injected
Intervention: Biological: hematopoietic stem cell transplantation
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
7
July 2016
July 2016   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Age ≥ 16 years and ≤ 65 years at the time of pretransplant evaluation.
  2. An established diagnosis of polymyositis, dermatomyositis, juvenile polymyositis/dermatomyositis, 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.
  3. 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.
  4. 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.

Exclusion Criteria:

  1. Poor performance (PS) status (ECOG >2) at the time of entry, unless decline of PS is due to the disease itself.
  2. 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.
  3. HIV positive.
  4. 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.
  5. 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.
  6. 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.
  7. Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible.
  8. Inability to give informed consent.
  9. Major hematological abnormalities such as platelet count less than 100,000/ul, ANC less than 1000/ul.
Sexes Eligible for Study: All
16 Years to 65 Years   (Child, Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00278564
NU FDA IIM.Auto2003
No
Not Provided
Plan to Share IPD: No
Richard Burt, MD, Northwestern University
Northwestern University
Not Provided
Principal Investigator: Richard Burt, MD Northwestern University
Northwestern University
July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP