Imatinib Mesylate (Gleevec) in the Treatment of Systemic Sclerosis
Condition: Systemic Sclerosis
MeSH terms: Scleroderma, Systemic; Scleroderma, Diffuse; Sclerosis
Intervention: Imatinib Mesylate
Intervention description: In initial phase, patients will be treated with Gleevec 400 mg daily for 12 months. In the extension phase, patients will be treated with Gleevec 400 mg daily for 27 months.
Intervention MeSH terms: Imatinib Mesylate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Systemic Sclerosis

Summary:

      The purpose of this study is to assess the safety and tolerability of imatinib mesylate
      (Gleevec) in patients with systemic sclerosis (scleroderma). Gleevec is a medication already
      FDA approved for the treatment of chronic myelogenous leukemia (CML), gastrointestinal
      stromal tumors (GIST), dermatofibrosarcoma protuberans tumors, Philadelphia
      chromosome-positive acute lymphoblastic leukemia, hypereosinophilic syndrome, and aggressive
      systemic mastocytosis. In-vitro studies have suggested that imatinib may inhibit collagen
      production by scleroderma fibroblasts, and in mouse models of fibrosis imatinib has been
      shown to decrease skin thickness.

      This is a Phase IIa, single center, prospective open label clinical trial of Gleevec in
      patients with systemic sclerosis. All patients will be treated with active drug for 12
      months. The primary objective of this study will be to determine the safety and tolerability
      of Gleevec in patients with systemic sclerosis, but important secondary outcomes of relevance
      will be improvement in disease status as defined by skin scores and indices of pulmonary
      function.

      Patients who complete the initial phase (described above) of the study will be eligible to
      participate in an extension phase. The purpose of the extension phase of the study is to give
      patients who participated in the phase IIa clinical trial of Gleevec at the Hospital for
      Special Surgery the opportunity to continue Gleevec treatment if both the treating physicians
      and the patient are in agreement that Gleevec had acceptable safety and tolerability, as well
      as possible efficacy during the initial year of therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age greater than or equal to eighteen years.

          2. Clinical diagnosis of diffuse systemic sclerosis by ACR criteria, with a stable
             modified Rodnan skin score in the one month preceding introduction of oral Gleevec
             therapy. The modified Rodnan skin score must be greater than or equal to sixteen at
             screening and initiation of therapy.

          3. Disease duration of less than or equal to 10 years.

          4. Estimated ejection fraction of greater than 50% by echocardiography

        Exclusion Criteria:

          1. Inability to render informed consent in accordance with institutional guidelines.

          2. Disease duration of greater than 10 years.

          3. Patients with mixed connective tissue disease or "overlap" (i.e. those who satisfy
             more than one set of ACR criteria for a rheumatic disease.)

          4. Ongoing treatment with other immunosuppressive therapies including cyclophosphamide,
             azathioprine, mycophenolic acid, methotrexate, or cyclosporine, or use of those
             medications within 3 months of trial entry.

          5. Concurrent serious medical condition which in the opinion of the investigator makes
             the patient inappropriate for this study such as uncontrollable CHF, arrhythmia,
             severe pulmonary or systemic hypertension, severe GI involvement, serum creatinine of
             greater than 2.0, active infection, severe diabetes, unstable atherosclerotic
             cardiovascular disease, malignancy, HIV, or severe peripheral vascular disease.

          6. The use of other anti-fibrotic agents including colchicine, D-penicillamine,
             minocycline, or Type 1 oral Collagen in the three months prior to enrollment.

          7. Limited scleroderma.

          8. Systemic sclerosis-like illness associated with environmental or ingested agents such
             as toxic rapeseed oil, vinyl chloride, or bleomycin.

          9. A positive pregnancy at entry into this study. Men and women with reproductive
             potential will be required to use effective means of contraception through the course
             of the study.

         10. Use in the prior month of corticosteroids at doses exceeding the equivalent of
             prednisone 10 mg daily. Use of corticosteroid at < 10 mg of prednisone can continue
             but not be increased during the course of the study.

         11. Participation in another clinical research study involving the evaluation of another
             investigational drug within ninety days of entry into this study.

         12. The presence of severe lung disease as defined by a diffusion capacity of less than
             30% of predicted.