Stem Cell Transplantation in Idiopathic Inflammatory Myopathy Diseases
Condition: MYOPATHY
MeSH terms: Muscular Diseases; Myositis
Intervention: Hematopoietic stem cell transplantation; Cyclophosphamide; Mesna; ATG(rabbit); Methylprednisolone; G-CSF; Rituxan
Intervention description: Autologous hematopoietic stem cell transplantation
Intervention MeSH terms: Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Cyclophosphamide; Rituximab; Prednisolone hemisuccinate; Prednisolone phosphate
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 16 Years
Maximum age: 65 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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, 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.

          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.