Expired Study
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New York, New York 10021


Purpose:

The purpose of this study is to assess the safety and tolerability of imatinib mesylate (Gleevec) in patients with systemic sclerosis (scleroderma). Gleevec is a medication already FDA approved for the treatment of chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GIST), dermatofibrosarcoma protuberans tumors, Philadelphia chromosome-positive acute lymphoblastic leukemia, hypereosinophilic syndrome, and aggressive systemic mastocytosis. In-vitro studies have suggested that imatinib may inhibit collagen production by scleroderma fibroblasts, and in mouse models of fibrosis imatinib has been shown to decrease skin thickness. This is a Phase IIa, single center, prospective open label clinical trial of Gleevec in patients with systemic sclerosis. All patients will be treated with active drug for 12 months. The primary objective of this study will be to determine the safety and tolerability of Gleevec in patients with systemic sclerosis, but important secondary outcomes of relevance will be improvement in disease status as defined by skin scores and indices of pulmonary function. Patients who complete the initial phase (described above) of the study will be eligible to participate in an extension phase. The purpose of the extension phase of the study is to give patients who participated in the phase IIa clinical trial of Gleevec at the Hospital for Special Surgery the opportunity to continue Gleevec treatment if both the treating physicians and the patient are in agreement that Gleevec had acceptable safety and tolerability, as well as possible efficacy during the initial year of therapy.


Study summary:

Further description of extension phase: Patients will first be evaluated for inclusion in the extension phase of the study at either the follow-up visit following three month withdrawal from Gleevec treatment or at the visit after the follow-up visit. Patients can undergo evaluation for inclusion in the extension phase up to six months following their completion of the initial one year trial. All patients evaluated for inclusion in the extension phase will sign a new informed consent form detailing the purpose and procedures associated with the extension phase at the initial visit. After the initial visit, patients who meet inclusion criteria will be required to undergo evaluation every three months for the 27 months following initiation of treatment, or more frequently if deemed clinically necessary. Treatment will consist of Gleevec, at doses ranging from 100 to 400 mg daily (100 mg pills will be distributed for oral administration). At each study visit, a history and physical exam will be performed and urine and blood tests will be conducted for disease activity and organ function. Additional blood for research may also be collected at study visits. The Modified Rodnan Skin Score will be measured to assess the degree of skin involvement associated with the patient's disease. Patients will also continue to complete questionnaires about their ability to function and quality of life. Patients will be financially responsible for all professional and clinical services, as well as all laboratory and diagnostic tests, associated with the extension phase of the study. All co-pays, deductibles and co-insurances will be paid by the participants. Any additional costs for parking and travel the patients incur as a result of participating in the extension phase will not be reimbursed by the study. Novartis Pharmaceuticals will donate drug supply.


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 Gleevec 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 10 years. 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 10 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. Ongoing treatment with other immunosuppressive therapies including cyclophosphamide, azathioprine, mycophenolic acid, methotrexate, or cyclosporine, or use of those medications within 3 months of trial entry. 5. 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, serum creatinine of greater than 2.0, active infection, severe diabetes, unstable atherosclerotic cardiovascular disease, malignancy, HIV, or severe peripheral vascular disease. 6. The use of other anti-fibrotic agents including colchicine, D-penicillamine, minocycline, or Type 1 oral Collagen in the three months prior to enrollment. 7. Limited scleroderma. 8. Systemic sclerosis-like illness associated with environmental or ingested agents such as toxic rapeseed oil, vinyl chloride, or bleomycin. 9. A positive pregnancy 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. 10. 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 but not be increased during the course of the study. 11. Participation in another clinical research study involving the evaluation of another investigational drug within ninety days of entry into this study. 12. The presence of severe lung disease as defined by a diffusion capacity of less than 30% of predicted.


Study is Available At:


Original ID:

27049


NCT ID:

NCT00555581


Secondary ID:


Study Acronym:


Brief Title:

Imatinib Mesylate (Gleevec) in the Treatment of Systemic Sclerosis


Official Title:

Phase IIA Study of the Safety and Tolerability of the Use of Imatinib Mesylate (Gleevec) in the Treatment of Systemic Sclerosis


Overall Status:

Completed


Study Phase:

Phase 2


Genders:

N/A


Minimum Age:

18 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Hospital for Special Surgery, New York


Oversight Authority:

  • United States: Institutional Review Board
  • United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

30


Enrollment Type:

Actual


Overall Contact Information

Official Name:Robert Spiera, MD
Principal Investigator
Hospital for Special Surgery, New York

Study Dates

Start Date:August 2007
Completion Date:December 2011
Completion Type:Actual
Primary Completion Date:December 2011
Primary Completion Type:Actual
Verification Date:January 2018
Last Changed Date:January 9, 2018
First Received Date:November 7, 2007
First Results Date:June 12, 2017

Study Outcomes

Outcome Type:Secondary Outcome
Measure:Change From Baseline at Month 12 in Short Form-36 (SF-36) Questionnaire: Physical Component Summary
Time Frame:12 months
Safety Issues:False
Description:The Short Form 36 (SF-36) is a 36 item questionnaire which measures quality of life across eight domains: physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, soci
Outcome Type:Secondary Outcome
Measure:Scleroderma Health Assessment Questionnaire Disability Index
Time Frame:12 months
Safety Issues:False
Description:The Scleroderma Health Assessment Questionnaire (SHAQ) consist of the Health Assessment Questionnaire (HAQ) and 8 other domains which include scales looking at pain, patient global assessment, vascular, digital ulcers, lung involvement, and gastrointestin
Outcome Type:Secondary Outcome
Measure:Change From Baseline at Month 12 in Short Form-36 (SF-36) Questionnaire:Mental Component Summary
Time Frame:12 months
Safety Issues:False
Description:The Short Form 36 (SF-36) is a validated 36 item questionnaire which measures quality of life across eight domains: physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-b
Outcome Type:Secondary Outcome
Measure:Improvement in Indices of Pulmonary Function Measured by Change DLCO hb Adj % Predicted
Time Frame:12 months
Safety Issues:False
Description:This outcome measure includes patients with and without the presence of Interstitial Lung Disease (ILD). Diffusion capacity of the lungs for carbon monoxide (DLCO) measures how much oxygen travels from the alveoli of the lungs to the blood stream. DLCO is
Outcome Type:Secondary Outcome
Measure:Improvement in Indices of Pulmonary Function Measured by Change in FVC % Predicted
Time Frame:12 months
Safety Issues:False
Description:This outcome measure includes patients with and without the presence of Interstitial Lung Disease (ILD). Forced vital capacity (FVC) is the amount of air that can be forcibly exhaled from the lungs after taking a deep breath. It is used to determine the s
Outcome Type:Primary Outcome
Measure:Improvement in the Modified Rodnan Skin Score
Time Frame:12 months
Safety Issues:False
Description:Improvement in the Modified Rodnan Skin Score (MRSS) is measured by Mean change (and 95% Confidence Interval) from Baseline mean to Month 12 mean.Measure Description: The Modified Rodnan Skin Score (MRSS) measures dermal skin thickness through the examina

Study Interventions

Intervention Type:Drug
Name:Imatinib Mesylate
Description:In initial phase, patients will be treated with Gleevec 400 mg daily for 12 months. In the extension phase, patients will be treated with Gleevec 400 mg daily for 27 months.
Arm Name:400 mg daily of Imatinib Mesylate

Study Arms

Study Arm Type:Experimental
Arm Name:400 mg daily of Imatinib Mesylate
Description:All patients were treated with imatinib mesylate at a target dose of 400 mg daily by mouth for 12 months. Dose modifications and interruptions were made for AE and were recorded. After 12 months of treatment, imatinib was stopped for 3 months. Patients were reassessed and offered entrance to an extension phase of the trial.

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Hospital for Special Surgery, New York
Agency Class:Industry
Agency Type:Collaborator
Agency Name:Novartis Pharmaceuticals

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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