High Dose Cyclophosphamide for Treatment of Scleroderma
Systemic Sclerosis (Scleroderma) varies greatly in clinical manifestations, mode of presentation, and course. The natural history of this chronic autoimmune disease ranges from benign to fatal. Patients are classified into limited and diffuse scleroderma defined by the degree of skin involvement. Patients with limited disease (e.g. the C.R.E.S.T. syndrome) generally have mild disease and normal survival. However, patients with diffuse cutaneous scleroderma often have severe multi-system disease that is not only devastating emotionally and physically but is associated with a 60-70% five year survival and a 40-50% 10 year survival. No therapies have proven effective in the treatment of scleroderma. Strategy to treat scleroderma have included attempts to prevent fibrosis with drugs that interfere with collagen metabolism, attempts to modify the disease process by immunosuppression and attempts to alter the disease by vasoactive drugs. High dose of corticosteroids and other immunosuppressive drugs (e.g. chlorambucil, 5-fluorouracil, methotrexate, cyclophosphamide, cyclosporine) used at conventional doses have not proven curative, but have shown some benefit for inflammatory features of the disease (e.g. arthritis, myositis, fibrosing alveolitis).
Both allogeneic and autologous bone marrow transplantation (BMT) have shown to modify and in some instances reverse a variety of animal models of autoimmune disease. This has prompted many investigators to propose the use of peripheral blood stem cell transplantation (PBSCT) for the treatment of autoimmune disease including scleroderma. Unfortunately, this approach risks infusing untreated autoreactive lymphocyte clones after the immunoablative preparative regimen. We have previously demonstrated that high-dose cyclophosphamide without BMT can induce durable and complete remissions in another autoimmune disease, severe aplastic anemia. Recent data with high dose cyclophosphamide show that it can induce complete remissions in other autoimmune hematologic disorders. The objective of this study is to determine whether high dose cyclophosphamide can induce a durable remission in scleroderma patients with life-threatening disease, and to determine toxicity of high dose cyclophosphamide in high risk scleroderma patients.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||High Dose Cyclophosphamide for Treatment of Systemic Sclerosis (Scleroderma)|
- The primary endpoint will be the total skin score. A 25% improvement will be considered clinically important. The skin score is the accepted clinical measure of scleroderma activity. [ Time Frame: 3 months through 3 years ] [ Designated as safety issue: No ]
- Secondary endpoints will be changes in the total severity score (composite) and measures of severity in each specific organ (organ specific measures). [ Time Frame: 3 months through 3 years ] [ Designated as safety issue: No ]
|Study Start Date:||February 2001|
|Study Completion Date:||May 2010|
|Primary Completion Date:||July 2008 (Final data collection date for primary outcome measure)|
This is an open-labeled single arm study.
Drug: High Dose Cyclophosphamide
Cyclophosphamide (50 mg/kg) intravenously daily for 4 consecutive days (total 200 mg/kg) followed by granulocyte colony-stimulating factor (5 µg/kg/day)