Imatinib Mesylate (Gleevec) in the Treatment of Systemic Sclerosis

NCT00555581 | Completed Phase 2 Results DMC

• 1 other identifier: 27049
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Systemic Sclerosis

Keywords

Systemic Sclerosis

Outcome Measures

Primary Outcomes (1)

• Improvement in the Modified Rodnan Skin Score

  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 examination of 17 body areas: fingers, hands, forearms, arms, feet, legs, and thighs (in pairs), and face, chest, and abdomen. The skin score is 0 for uninvolved skin through 3 for severe thickening (hidebound skin). The total skin score is the sum of the skin scores of the individual areas. The minimum score is 0 and the maximum score is 51. A higher score indicates greater severity of disease. The mean change in MRSS represents the average change in total skin score from baseline to month 12.

  12 months

Secondary Outcomes (5)

• Improvement in Indices of Pulmonary Function Measured by Change in FVC % Predicted

  12 months

• Improvement in Indices of Pulmonary Function Measured by Change DLCO hb Adj % Predicted

  12 months

• Change From Baseline at Month 12 in Short Form-36 (SF-36) Questionnaire:Mental Component Summary

  12 months

• Scleroderma Health Assessment Questionnaire Disability Index

  12 months

• Change From Baseline at Month 12 in Short Form-36 (SF-36) Questionnaire: Physical Component Summary

  12 months

Study Arms (1)

400 mg daily of Imatinib Mesylate

EXPERIMENTAL

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.

Drug: Imatinib Mesylate

Interventions

Imatinib Mesylate DRUG

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.

400 mg daily of Imatinib Mesylate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than or equal to eighteen years.
• 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.
• Disease duration of less than or equal to 10 years.
• Estimated ejection fraction of greater than 50% by echocardiography

You may not qualify if:

• Inability to render informed consent in accordance with institutional guidelines.
• Disease duration of greater than 10 years.
• Patients with mixed connective tissue disease or "overlap" (i.e. those who satisfy more than one set of ACR criteria for a rheumatic disease.)
• 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.
• 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.
• The use of other anti-fibrotic agents including colchicine, D-penicillamine, minocycline, or Type 1 oral Collagen in the three months prior to enrollment.
• Limited scleroderma.
• Systemic sclerosis-like illness associated with environmental or ingested agents such as toxic rapeseed oil, vinyl chloride, or bleomycin.
• 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.
• 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.
• Participation in another clinical research study involving the evaluation of another investigational drug within ninety days of entry into this study.
• The presence of severe lung disease as defined by a diffusion capacity of less than 30% of predicted.

Sponsors & Collaborators

• Hospital for Special Surgery, New York: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Hospital for Special Surgery

New York, New York, 10021, United States

Location

Related Publications (2)

• Haddon DJ, Wand HE, Jarrell JA, Spiera RF, Utz PJ, Gordon JK, Chung LS. Proteomic Analysis of Sera from Individuals with Diffuse Cutaneous Systemic Sclerosis Reveals a Multianalyte Signature Associated with Clinical Improvement during Imatinib Mesylate Treatment. J Rheumatol. 2017 May;44(5):631-638. doi: 10.3899/jrheum.160833. Epub 2017 Mar 15.

  PMID: 28298564 DERIVED

• Spiera RF, Gordon JK, Mersten JN, Magro CM, Mehta M, Wildman HF, Kloiber S, Kirou KA, Lyman S, Crow MK. Imatinib mesylate (Gleevec) in the treatment of diffuse cutaneous systemic sclerosis: results of a 1-year, phase IIa, single-arm, open-label clinical trial. Ann Rheum Dis. 2011 Jun;70(6):1003-9. doi: 10.1136/ard.2010.143974. Epub 2011 Mar 11.

  PMID: 21398330 DERIVED

Related Links

• Clinical Trials - HSS
• Related Info

MeSH Terms

Conditions

Scleroderma, Systemic

Interventions

Imatinib Mesylate

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Results Point of Contact

• Title: Robert F. Spiera
• Organization: Hospital for Special Surgery

spierar@hss.edu

212-774-2048

Study Officials

• Robert Spiera, MD

  Hospital for Special Surgery, New York

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2007
• First Posted: November 8, 2007
• Study Start: August 1, 2007
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: February 6, 2018
• Results First Posted: February 6, 2018

Record last verified: 2018-01

Locations

US (1)