Autologous Stem cell Transplantation International Scleroderma ('ASTIS') Trial.

This multicenter prospective randomized controlled phase III study will compare efficacy and safety of high dose immunoablation and autologous hematopoietic stem cell transplantation (HSCT) (considered the investigational treatment), versus monthly intravenous pulse-therapy cyclophosphamide (considered the control treatment) in selected patients with diffuse systemic sclerosis at risk for premature mortality.

The primary endpoint is event-free survival defined as the time in days from the day of randomization until the occurrence of death or the development of persistent major organ failure (heart, lung, kidney) during the study period of 2 years. It is intended to enrol 200 patients and to have an annual follow up of each patient for at least 5 years.

It is postulated that the investigational treatment has superior efficacy based on observations of longterm remissions in a number of patients, although this has to be balanced against potentially higher toxicity.

This multicenter prospective randomized controlled phase III study compares efficacy and safety of high dose immunoablation and autologous hematopoietic stem cell transplantation (HSCT) (considered the investigational treatment), versus monthly intravenous pulse-therapy cyclophosphamide (considered the control treatment).
The investigational treatment arm comprises the following consecutive steps: mobilization of hematopoietic stem cells with i.v. cyclophosphamide (2x2 gr/m2) and filgrastim (10 mg/kg/day), leukapheresis and selection of CD34+ stem cells, conditioning with i.v. cyclophosphamide (200 mg/kg) and rbATG (7.5 mg/kg), followed by HSCT.
The procedures are normally completed within 3-4 months after randomization. The control treatment arm consists of 12 consecutive monthly i.v. pulses cyclophosphamide (750 mg/m2).