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

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ClinicalTrials.gov Identifier: NCT00512902
Recruitment Status : Completed
First Posted : August 8, 2007
Results First Posted : October 27, 2014
Last Update Posted : October 27, 2014
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Daniel Furst, University of California, Los Angeles

Brief Summary:
The purpose of this study is to assess the safety and tolerability of imatinib (gleevec) in subjects who have systemic sclerosis. Imatinib has been approved by the FDA for the treatment of newly diagnosed adult patients with CML (newly diagnosed adult patients and for the treatment of patients with an accelerated phase. Imatinib is also approved for the treatment of patients with a certain type of gastrointestinal cancer (called stromal tumors) but it has not been approved to treat systemic sclerosis. Imatinib works by interfering with an enzyme called tyrosine phosphatase resulting in suppression of the immune system. It als interferes with a protein called platelet derived growth factor receptor (PDGFr) that has been linked to increased fibrosis.

Condition or disease Intervention/treatment Phase
Alveolitis Systemic Sclerosis Drug: Imatinib Phase 1 Phase 2

Detailed Description:
Systemic sclerosis is a rare, progressive disease that leads to hardening and tightening of the skin and connective tissues. It usually begins with a few dry patches of skin on the hands or face that begin getting thicker and harder. These patches then spread to other areas of the skin. In some cases, systemic sclerosis also affects the blood vessels an internal organs. Systemic sclerosis is one of a group of arthritic conditions called connective tissue disorders, a person's antibodies are directed against their own tissues.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study to Examine The Use of Imatinib (Gleevec) For The Treatment of Active Alveolitis in Systemic Sclerosis
Study Start Date : August 2007
Actual Primary Completion Date : November 2008
Actual Study Completion Date : December 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Scleroderma

Arm Intervention/treatment
Experimental: Group 1
SSc patients receiving Imatinib (Gleevec, up to 600 mg) QD PO for up to 1 year.
Drug: Imatinib
All subjects will receive gleevec. Subjects will have a clinic visit every 2 weeks for the first 20 weeks and then they will have one every 4 weeks for the remainder of the study. Gleevec will be taken by mouth everyday. It will be increased to a maximum of 600 mg every day. It will be increased 100 mg at each visit for the first 12 weeks. Your participation may last up to 1 year and participants will have approximately 18 clinic visits.
Other Name: Gleevec

Drug: Imatinib
Up to 600 mg QD PO for up to 1 year.
Other Name: Gleevec

Primary Outcome Measures :
  1. Treatment-related Adverse Events [ Time Frame: Baseline vs. Endpoint (1 year) ]
    Treatment-related adverse events requiring discontinuation.

Secondary Outcome Measures :
  1. Change in FVC (Forced Vital Capacity) [ Time Frame: Baseline vs. Endpoint (1 year) ]
    Measures the amount of air breathed out as a percent of predicted.

  2. Change in TLC (Total Lung Capacity) [ Time Frame: Baseline vs. Endpoint (1 year) ]
    No measures of dispersion was available for TLC as data were lost. This describes the total lung capacity as a percent of predicted.

  3. Change in DLco [ Time Frame: Baseline vs. Endpoint (1 year) ]
    DLCO (diffusing capacity or transfer factor of the lung for carbon monoxide (CO)) is the extent to which oxygen passes from the air sacs of the lungs into the blood. Commonly, it refers to the test used to determine this parameter.

  4. Change in Modified Rodnan Skin Score (MRSS) [ Time Frame: Baseline vs. Endpoint ]
    No measures of dispersion was available as data were lost. The range of this measure is 0 to 51 and measures the extent of skin thickening with higher numbers representing thickening.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00512902

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United States, California
UCLA David Geffen School of Medicine, Division of Rheumatology
Los Angeles, California, United States, 90095
Sponsors and Collaborators
University of California, Los Angeles
Novartis Pharmaceuticals
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Principal Investigator: Daniel E. Furst, MD University of California, Los Angeles
Publications of Results:
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Responsible Party: Daniel Furst, M.D., Carl M Pearson Professor of Rheumatology, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT00512902    
Other Study ID Numbers: CST1571EUS210
First Posted: August 8, 2007    Key Record Dates
Results First Posted: October 27, 2014
Last Update Posted: October 27, 2014
Last Verified: October 2014
Keywords provided by Daniel Furst, University of California, Los Angeles:
active alveolitis in systemic sclerosis
Additional relevant MeSH terms:
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Scleroderma, Systemic
Scleroderma, Diffuse
Pathologic Processes
Connective Tissue Diseases
Skin Diseases
Imatinib Mesylate
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action