A Study Using The Experimental Drug Called Imatinib (Gleevec) in Subjects With Systemic Sclerosis

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 componentof the Mahler Modified Dyspnea Index).

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

7. Patients may have limited (cutaneous thickening distal but not proximal to elbows andknees, with or without facial involvement) or diffuse (cutaneous thickening proximalto 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 whichshows ground glass opacification as a radiographic marker of "alveolitis" or finelyreticulated 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 7days 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 significantpulmonary 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 heartcatheterization (i.e., right ventricular systolic pressure of >50 mm Hg and/or meanPAP ≥30 mm Hg) pulmonary pressure or echocardiographic evidence of PAH (if echocardiographic systolic pressure ≥ 55 mmHg) or FVC/DLCO ratio >1.6 on pulmonaryfunction testing

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

6. History of persistent leukopenia (white blood cell count <3500), neutropenia (absoluteneutrophil 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 ofcontraception

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

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 havebeen 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 otherprimary malignancy is not currently clinically significant nor requiring activeintervention, or if other primary malignancy is a basal cell skin cancer or a cervicalcarcinoma in situ. Existence of any other malignant disease is not allowed exceptafter consultation with the PI.

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

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

23. Use of contraindicated medications at baseline.