Nilotinib in the Treatment of Systemic Sclerosis
Condition: Systemic Sclerosis
MeSH terms: Scleroderma, Systemic; Scleroderma, Diffuse; Sclerosis
Intervention: Nilotinib (Tasigna)
Intervention description: Patients will be treated with Nilotinib 400 mg two times a day for 6 months.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Systemic Sclerosis

Summary:

      A phase IIa open-label single center pilot study to assess the safety and efficacy of
      Nilotinib in patients with Scleroderma.
    

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 nilotinib
             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 3 years as defined by the date of onset of
             the first non-Raynaud's symptom.

          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 3 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. Limited scleroderma.

          5. Systemic sclerosis-like illness associated with environmental or ingested agents such
             as toxic rapeseed oil, vinyl chloride, or bleomycin.

          6. Ongoing treatment with immunosuppressive therapies including cyclophosphamide,
             azathioprine, mycophenolic acid, methotrexate, or cyclosporine, or use of those
             medications within 1 month of trial entry.

          7. The use of other anti-fibrotic agents including colchicine, D-penicillamine,
             minocycline, or Type 1 oral Collagen in the month prior to enrollment.

          8. 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
             during the course of the study.

          9. 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, hepatic impairment,
             serum creatinine of greater than 2.0, active infection, severe diabetes, unstable
             atherosclerotic cardiovascular disease, malignancy, HIV, or severe peripheral vascular
             disease.

         10. History of pancreatitis.

         11. Prolonged QTc interval defined as a QTc > 450 msec

         12. Patients requiring the ongoing use of medications that are antiarrhythmics (including,
             but not limited to amiodarone, disopyramide, procainamide, quinidine and sotalol) or
             that prolong the QTc interval (including, but not limited to chloroquine,
             halofantrine, clarithromycin, haloperidol, methadone, moxifloxacin, bepridil and
             pimozide) will be excluded.

         13. Patients requiring the ongoing use of medications that are potent inhibitors or
             inducers of CYP3A4.

         14. A positive pregnancy test 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.

         15. Participation in another clinical research study involving the evaluation of another
             investigational drug within ninety days of entry into this study.

         16. The presence of severe lung disease as defined by a diffusion capacity of less than
             30% of predicted.