Clinical trial NCT00278525
Conditions: SYSTEMIC SCLERODERMA
Sponsor: Northwestern University
Start date: 2005-09-01; Completion date: 2012-12-01
Enrollment: 19 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Scleroderma is a systemic disorder categorized as an immunologically mediated disease that causes collagen deposition of skin and visceral organs. The molecular pathogenesis of scleroderma has been elusive, although vasculopathy and immune mediated mechanisms are thought to be important. Once extensive cutaneous or visceral disease occurs, prognosis is significantly shorter than the general population. Although various treatments have been tried, none of them seems to have changed the natural history of scleroderma. Standard dose immunosuppressive treatment has been disappointing. Recently, cyclophosphamide at 1-2 mg/kg/day orally or 800-1400 mg intravenous (IV) monthly for 6-9 months has proven effective in treatment of scleroderma alveolitis (1). Recent phase I studies of immunoablation with autologous peripheral blood stem cell transplantation (PBSCT) showed some promising data, but the exact efficacy is undetermined (2,3). We now propose, as a phase II randomized study, autologous unmanipulated PBSCT versus pulse cyclophosphamide in patients with systemic scleroderma.

Detailed description:
To evaluate the efficacy of two treatment modalities: pulse cyclophosphamide versus high dose cyclophosphamide and anti-thymocyte globulin (ATG) rescued with autologous peripheral blood stem cell transplantation (PBSCT). The primary endpoints to be considered in this study are:

I)Time to Treatment Failure -Treatment failure will not occur until a minimum of 12 months after enrollment at which time failure is defined as:

1. Failure of skin score (if \> 14 on enrollment) to improve or increase in skin score by a 25% above lowest post treatment value and must be documented on 2 occasion 6 months apart
2. Deterioration in diffusing capacity of the lung for carbon monoxide (DLCO), diffusing capacity divided by the alveolar volume (DLCO/VA) or forced vital capacity (FVC) by 10% below enrollment level or 10% below best post treatment value, due to systemic sclerosis, and documented on 2 occasion 6 months apart
3. Renal failure due to systemic sclerosis and defined as chronic dialysis for more than 12 months
4. Gastrointestinal failure due to systemic sclerosis and defined as initiation of total parenteral nutrition (TPN) for more than 12 months

II) Disease improvement defined by at least 25% improvement in skin score (Rodnan), or 10% improvement in pulmonary function tests (DLCO, DLCO/VA, or FVC), or in cardiac tests \[pulmonary artery (PA) systolic pressure by right heart cath) that persists \> 6 months or ability to wean off TPN

Arms: arm 1: intervention as stem cell transplantation after conditioning regimen arm 2: medication as standard of care will be given
Interventions: intervention 1: standard of care intervention 2: stem cell transplantation
Intervention descriptions: intervention 1: standard of care medication will be given intervention 2: The following is intervention: stem cell transplantation after conditioning regimen

Protocol documents: