High Dose Cyclophosphamide for Treatment of Scleroderma
Status:
Completed
Trial end date:
2010-05-01
Target enrollment:
Participant gender:
Summary
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.