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

NCT00512902 | Completed Phase 1 Results

• 1 other identifier: CST1571EUS210
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Alveolitis; Systemic Sclerosis

Keywords

active alveolitis in systemic sclerosis

Outcome Measures

Primary Outcomes (1)

• Treatment-related Adverse Events

  Treatment-related adverse events requiring discontinuation.

  Baseline vs. Endpoint (1 year)

Secondary Outcomes (4)

• Change in FVC (Forced Vital Capacity)

  Baseline vs. Endpoint (1 year)

• Change in TLC (Total Lung Capacity)

  Baseline vs. Endpoint (1 year)

• Change in DLco

  Baseline vs. Endpoint (1 year)

• Change in Modified Rodnan Skin Score (MRSS)

  Baseline vs. Endpoint

Study Arms (1)

Group 1

EXPERIMENTAL

SSc patients receiving Imatinib (Gleevec, up to 600 mg) QD PO for up to 1 year.

Drug: Imatinib

Interventions

Imatinib DRUG

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.

Also known as: Gleevec

Group 1

Eligibility Criteria

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

You may qualify if:

• All patients must fulfill the criteria for SSc by ACR criteria
• Age of entry into the study ≥ 18 yrs
• FVC \<85% of predicted.
• Able to complete the 6MWT with a walking distance ≥ 150 m
• Patients must have dyspnea on exertion (grade ≥ 2 on the Magnitude of Task component of the Mahler Modified Dyspnea Index).
• SSc for ≤ 10 years, with onset defined as the date of the first non-Raynaud manifestation typical of systemic sclerosis.
• 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).
• 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).
• Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing.
• Patients must be able to provide written voluntary informed consent.

You may not qualify if:

• 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).
• FEV1/FVC ratio \<65% (to exclude significant airflow obstruction)
• Clinically significant abnormalities on HRCT not attributable to SSc (e.g., lung mass, extensive scarring due to previous infection, etc.)
• 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
• Persistent unexplained hematuria (\>10 RBCs/hpf).
• History of persistent leukopenia (white blood cell count \<3500), neutropenia (absolute neutrophil count \< 1500) or thrombocytopenia (platelet count \<100,000).
• Clinically significant anemia (\<9.0 gm/dl)
• Serum creatinine \>ULN.
• Pregnancy (documented by urine pregnancy test), breast feeding
• If of child-bearing potential, failure regularly to employ a reliable means of contraception
• Active infection of the lung or elsewhere, whose management would be compromised by Imatinib
• Unreliability, drug abuse (including active alcoholism)
• Any chronic, debilitating illness (other than SSc)
• Smoking of cigars, pipes or cigarettes during the past 6 months
• Baseline liver function tests (ALT or AST or bilirubin \>1.5 x upper limit of normal

Sponsors & Collaborators

• University of California, Los Angeles: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

UCLA David Geffen School of Medicine, Division of Rheumatology

Los Angeles, California, 90095, United States

Location

Related Publications (1)

• Khanna D, Saggar R, Mayes MD, Abtin F, Clements PJ, Maranian P, Assassi S, Saggar R, Singh RR, Furst DE. A one-year, phase I/IIa, open-label pilot trial of imatinib mesylate in the treatment of systemic sclerosis-associated active interstitial lung disease. Arthritis Rheum. 2011 Nov;63(11):3540-6. doi: 10.1002/art.30548.

  PMID: 21769849 RESULT

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

Limitations and Caveats

Open label, small.

Results Point of Contact

• Title: Dr. Daniel Furst, Carl M Pearson Professor of Rheumatology
• Organization: University of California at Los Angeles

defurst@mednet.ucla.edu

310-794-9504

Study Officials

• Daniel E. Furst, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., Carl M Pearson Professor of Rheumatology

Study Record Dates

• First Submitted: August 6, 2007
• First Posted: August 8, 2007
• Study Start: August 1, 2007
• Primary Completion: November 1, 2008
• Study Completion: December 1, 2008
• Last Updated: October 27, 2014
• Results First Posted: October 27, 2014

Record last verified: 2014-10

Locations

US (1)