Institutional Review Board, Hospital for Special Surgery
September 26, 2007
The safety of study participants is our top priority. The trial is approved and periodically reviewed by an Institutional Review Board (IRB), which includes doctors, administrators, ethicists, and members of the general public. The safety of clinical trials is reviewed by the U.S. Food and Drug Administration.
Before enrolling in a clinical trial, the investigator will explain the purpose of the trial, its expected benefits, any possible risks or side effects, and what your role will be. This is the time to ask questions! If you want to join the trial, you must sign the informed consent documents. You can leave a clinical trial at any time without penalty.
For further information, see Understanding Clinical Trials.
Mary K. Crow, MD
Jessica Gordon, MD
Kyriakos A. Kirou, MD
Stephen Lyman, PhD
Cynthia Magro, MD
Emma MacDermott, MD
Horatio F. Wildman, MD
Rolando Duculan, MD
Morgana Davids, BA
Kamini Doobay, BA
Danielle Citrolo, Pharm.D
Uzunma Udeh, BA
Nina Paddu, BA
Daniele Lerner, BA
The purpose of this study is to learn about how safe and tolerable a medication called Gleevec will be for patients diagnosed with systemic sclerosis. Gleevec is a medication already on the market that has been FDA approved for the treatment of a type of leukemia (“CML”- chronic myelogenous leukemia), a type of gastrointestinal tumor (stromal tumor), and a syndrome characterized by an excess amount of a certain type of white blood cell (Hypereosinophilia syndrome). It is not FDA approved to treat scleroderma or other autoimmune diseases at this time. It is an oral medication, taken as a daily pill. This Phase IIa clinical trial is being conducted to assess the tolerability and safety of Gleevec in patients with SSc. This study may or may not be able to show whether or not Gleevec is a good treatment for SSc. Your overall participation will be over a period of 16 months.
All study visits will be done at this study site. The visit length will vary according to type of study visit. You will be evaluated one month prior to trial entry, at the initiation of treatment, every month for one year, and three months after withdrawal of study medication. Treatment will consist of Gleevec, one 400mg tablet taken by mouth daily. 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. The Modified Rodnan Skin Score will be measured to assess the degree of skin involvement associated with your disease. Pulmonary function tests and chest radiographs will occur at baseline and at one year to help your study doctor determine any scleroderma lung involvement at study entry and during the trial. Two 4 mm punch biopsies of lesional skin will be obtained at baseline and at 12 months to also assess the degree of skin involvement. Other information collected at each study visit will be questionnaires that you will be asked to complete, which help to measure features related to your function and quality of life.
Patients who complete the 16-month initial phase 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.
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.
You must meet the following conditions in order to participate in this study:
• You must be eighteen years or older.
• You have been clinically diagnosed with diffuse systemic sclerosis according to the ACR criteria, and have a stable modified Rodnan skin score in the one month prior to taking Gleevec.
• Your modified Rodnan skin score is greater than or equal to sixteen at screening and initiation of therapy.
• You have systemic sclerosis for less than or equal to 10 years.
If you meet any of the following conditions, you should not be in this study:
1. You have had systemic sclerosis for more than 10 years.
2. A modified Rodnan skin score of less than sixteen at screening and initiation of therapy.
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.) Mixed connective tissue disease is classically considered as an "overlap" of three diseases; systemic lupus erythematosus, scleroderma, and polymyositis. Patients with this pattern of illness have features of each of these three diseases. Only if you have been diagnosed with diffuse scleroderma can you be included in the study.
4. You are receiving 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. You have other serious medical conditions that would possibly make it dangerous for you to receive this drug.
6. You have used other anti-fibrotic agents including colchicine, D-penicillamine, minocycline, or Type 1 oral Collagen within 3 months of trial entry.
7. You have limited scleroderma.
8. You have a systemic sclerosis-like illness associated with environmental or ingested agents such as toxic rapeseed oil, vinyl chloride, or bleomycin.
9. You are a woman who is pregnant you may not participate in this study. You must confirm that, to the best of your knowledge, you are not now pregnant, and that you do not intend to become pregnant during the course of this study. Men and women with reproductive potential will be required to use effective means of contraception through the course of the study. If you suspect that you have become pregnant during this study, you must notify the study doctor immediately.
10. You have used more than 10mg daily of corticosteroids within the last month. Using corticosteroid at < 10 mg of prednisone can continue but may not be increased during the course of the study.
11. You have participated in another clinical research study involving the evaluation of another investigational drug within ninety days of entry into this study.
12. There is presence of severe lung disease.
13. Estimated ejection fraction of less than 50% by echocardiography. (The term "ejection fraction" refers to the percentage of blood that's pumped out of a filled ventricle with each heartbeat. This measures the capacity at which your heart is pumping. A normal ejection fraction is greater than 50%.) This will be performed at your screening if you haven’t had one in the last 4 weeks as part of your standard of care.
**Please note that enrollment into this study has completed.
Inclusion Criteria for extension phase:
Any participant who completed the initial phase of the study can be evaluated by the treating physicians for inclusion in the extension phase of the study.
Exclusion Criteria for extension phase:
• Other serious medical conditions that would possibly make it dangerous for the participant to receive study medication.
• A positive pregnancy at entry of the extension phase of the study. Men and women with reproductive potential will be required to use effective means of contraception through the course of the study.
• Participation in another clinical research study involving the evaluation of an investigational drug within ninety days of entry.
• Estimated ejection fraction of less than 50% by echocardiography.
• Intolerable or dangerous side effects related to the use of Gleevec during the initial year of treatment.