Proof of Concept Trial of Gleevec (Imatinib) in Active Diffuse Scleroderma

• Status: Terminated
• Trial end date: 2008-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to investigate the effectiveness and safety of the drug Gleevec (imatinib) as a new treatment for patients with active diffuse scleroderma. This drug has not been used previously to treat scleroderma, but it has been found to advance the treatment and life span of patients with a type of leukemia called chronic myeloid leukemia or CML. Gleevec acts on chemical signals in the cells that may decrease fibrosis (the hardening of the skin that occurs in scleroderma). It works by interfering in the process that activates many molecules that cause fibrosis, including TGFbeta (which may be a key part of disease activity in scleroderma).

This study proposes to treat patients that have significant diffuse scleroderma with Gleevec for 6 months and investigate several measures of scleroderma disease activity before, during and at the end of treatment (0, 3 months and 6 months). This is a randomized, double blind, placebo-controlled trial: 20 patients will be divided into two groups in a 4:1 ratio, with 16 patients taking 400mg of Gleevec per day and 4 taking a placebo. The differences between the groups that will be measured include safety, Modified Rodnan skin score (mRSS), Health Assessment Questionnaire (HAQ), global assessments (100mm VAS) and changes in biomarkers in blood and skin biopsies.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Lawson Health Research Institute
• Collaborator: Novartis Pharmaceuticals
• Treatments: Imatinib Mesylate

Criteria

Inclusion Criteria:

• Subjects must be able to give informed consent.

• Subjects must meet preliminary criteria for scleroderma.

• Subjects must have diffuse skin involvement.

• Disease must appear to be active as measured by worsening skin score and/or increased ESR.

• Serum SGOT < 1.5 times upper limit of normal.

• Bilirubin < 1.5 times upper limit of normal.

• AST/ALT < 2.5 times upper limit of normal

Exclusion Criteria:

• Any past exposure to Gleevec.

• Women of child bearing potential must be practicing an acceptable form of contraception (OCP, depo-provera, IUD, condoms with spermicidal or sterilization of subject or partner).

• Women who are breastfeeding.

• Men whose partners could conceive must be practicing acceptable contraception (see above).

• Certain abnormal labs including: Neutrophil count <1.5X109/L, platelets < 50X109/L.

• Serious comorbidity that may impair the ability to complete the study (such as severe heart disease, severe pulmonary hypertension) and other comorbidities.

• Prednisone at doses of >10mg/od.

• Other potential disease modifying drugs such as cyclophosphamide, mycophenylate and methotrexate.

• Serious liver disease.

• Creatinine >200.

• Excluded: Ketoconazole and fluconazole, cyclosporine, rifampin, phenytoin nefazodone, pimozide, propafenone, quinidine, sibutramine and sildenafil where drug interactions could occur.

• Subjects taking endothelin receptor blockers such as bosentan and sitaxsentan.

• Alcohol consumption of > 3 drinks per week.