Clinical trial NCT00512902 (phase 1/phase 2, status: completed)
Conditions: alveolitis, systemic sclerosis
ICD codes: M34.0, M34.89, M34.9, M34.82, M34.83, M34.81, M34.2
Drugs: imatinib, imatinib
SMILES: CC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC1, CC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC1
Eligibility criteria:

        Inclusion Criteria:

          1. All patients must fulfill the criteria for SSc by ACR criteria

          2. Age of entry into the study ≥ 18 yrs

          3. FVC <85% of predicted.

          4. Able to complete the 6MWT with a walking distance ≥ 150 m

          5. Patients must have dyspnea on exertion (grade ≥ 2 on the Magnitude of Task component
             of the Mahler Modified Dyspnea Index).

          6. SSc for ≤ 10 years, with onset defined as the date of the first non-Raynaud
             manifestation typical of systemic sclerosis.

          7. Patients may have limited (cutaneous thickening distal but not proximal to elbows and
             knees, with or without facial involvement) or diffuse (cutaneous thickening proximal
             to elbows and knees, often involving the chest or abdomen) cutaneous SSc (Medsger
             1995).

          8. Patients must show some evidence of alveolitis as defined by an HRCT of the lung which
             shows ground glass opacification as a radiographic marker of "alveolitis" or finely
             reticulated fibrosis or they must have alveolitis by BAL ( ≥ 3% PMN's or ≥ 2%
             eosinophils).

          9. Female patients of childbearing potential must have negative pregnancy test within 7
             days before initiation of study drug dosing.

         10. Patients must be able to provide written voluntary informed consent.

        Exclusion Criteria:

          1. FVC ≤ 50% of predicted or DLCO (corrected for Hgb but not for alveolar volume) ≤ 35%
             of predicted (suggesting severe probably irreparable disease and/or significant
             pulmonary vascular involvement by SSc).

          2. FEV1/FVC ratio <65% (to exclude significant airflow obstruction)

          3. Clinically significant abnormalities on HRCT not attributable to SSc (e.g., lung mass,
             extensive scarring due to previous infection, etc.)

          4. Clinically significant pulmonary hypertension documented on right heart
             catheterization (i.e., right ventricular systolic pressure of >50 mm Hg and/or mean
             PAP ≥30 mm Hg) pulmonary pressure or echocardiographic evidence of PAH (if echo
             cardiographic systolic pressure ≥ 55 mmHg) or FVC/DLCO ratio >1.6 on pulmonary
             function testing

          5. Persistent unexplained hematuria (>10 RBCs/hpf).

          6. History of persistent leukopenia (white blood cell count <3500), neutropenia (absolute
             neutrophil count < 1500) or thrombocytopenia (platelet count <100,000).

          7. Clinically significant anemia (<9.0 gm/dl)

          8. Serum creatinine >ULN.

          9. Pregnancy (documented by urine pregnancy test), breast feeding

         10. If of child-bearing potential, failure regularly to employ a reliable means of
             contraception

         11. Active infection of the lung or elsewhere, whose management would be compromised by
             Imatinib

         12. Unreliability, drug abuse (including active alcoholism)

         13. Any chronic, debilitating illness (other than SSc)

         14. Smoking of cigars, pipes or cigarettes during the past 6 months

         15. Baseline liver function tests (ALT or AST or bilirubin >1.5 x upper limit of normal

         16. Previous use of prednisone > 10 mg per day. If on prednisone ≤10 mg/d, dose must have
             been stable for > 1 month.

         17. All other medication with putative disease-modifying properties (e.g.,
             D-penicillamine, cyclophosphamide, azathioprine, methotrexate, colchicine, Potaba)
             must be discontinued 1 month prior to beginning study medication.

         18. Patient is < 5 years since she/he had a primary malignancy except: if the other
             primary malignancy is not currently clinically significant nor requiring active
             intervention, or if other primary malignancy is a basal cell skin cancer or a cervical
             carcinoma in situ. Existence of any other malignant disease is not allowed except
             after consultation with the PI.

         19. Patient with Grade III/IV cardiac problems as defined by the New York Heart
             Association Criteria. (i.e., congestive heart failure, myocardial infarction within 6
             months of study)

         20. Patient has a severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes,
             chronic renal disease, or active uncontrolled infection).

         21. Patient has known chronic liver disease (i.e., chronic active hepatitis and
             cirrhosis).

         22. Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.

         23. Use of contraindicated medications at baseline.