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

This study has been completed.
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Daniel Furst, University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT00512902
First received: August 6, 2007
Last updated: August 25, 2011
Last verified: August 2011
  Purpose

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 Intervention
Alveolitis
Systemic Sclerosis
Drug: Gleevec

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of California, Los Angeles:

Primary Outcome Measures:
  • Patients will be compared with respect to efficacy measures and adverse events. [ Time Frame: Baseline vs. Endpoint ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 20
Study Start Date: August 2007
Study Completion Date: December 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Gleevec
    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 you will have approximately 18 clinic visits.
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. All patients must fulfill the criteria for SSc by ACR criteria (Subcommittee for Scleroderma Criteria 1980).
  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. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug.
  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 be employing a reliable means of contraception (i.e., condom, abstinence, IUD, tubal ligation, vasectomy)
  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) which might compromise the patient's participation in the trial.
  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. If used, need to be discussed with PI, attempts made to find a substitute, documented and kept stable throughout. (see appendix 1).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00512902

Locations
United States, Texas
The University of Texas
Houston, Texas, United States, 77030
Sponsors and Collaborators
University of California, Los Angeles
Novartis Pharmaceuticals
Investigators
Principal Investigator: Daniel E. Furst, MD University of California, Los Angeles
  More Information

No publications provided by University of California, Los Angeles

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Daniel Furst, M.D., Carl M Pearson Professor of Rheumatology, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT00512902     History of Changes
Other Study ID Numbers: CST1571EUS210
Study First Received: August 6, 2007
Last Updated: August 25, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, Los Angeles:
active alveolitis in systemic sclerosis

Additional relevant MeSH terms:
Scleroderma, Systemic
Scleroderma, Diffuse
Sclerosis
Connective Tissue Diseases
Skin Diseases
Pathologic Processes
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 01, 2014