No registrations found.
ID
Source
Brief title
Health condition
Systemic sclerosis.
Sponsors and support
Intervention
Outcome measures
Primary outcome
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.
Secondary outcome
Key secondary outcomes include: treatment related mortality, treatment toxicity, and progression-free survival, defined as the time in days since the day of randomization until death or predefined changes in skin score, organ function, body weight, functional disability from baseline has been documented at two consecutive 3-month evaluations within the study period of 2 years.
Background summary
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.
Study objective
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.
Intervention
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).
Department of Rheumatology,
P.O. Box 9600
J.M. Laar, van
Leiden 2300 RC
The Netherlands
+31 (0)71 5263598
j.m.van_laar@lumc.nl
Department of Rheumatology,
P.O. Box 9600
J.M. Laar, van
Leiden 2300 RC
The Netherlands
+31 (0)71 5263598
j.m.van_laar@lumc.nl
Inclusion criteria
Patients with diffuse systemic sclerosis, aged 16-65 yrs, and:
1. Disease duration 4 years or less, plus evidence of heart, lung or kidney involvement, plus skin score 15 or more, or:
2. Disease duration 2 years or less, plus evidence of an acute phase reaction in blood, plus skin score 20 or more.
Exclusion criteria
Patients with concomitant severe disease, extensive pretreatment according to predefined criteria with cyclophosphamide are excluded.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL300 |
| NTR-old | NTR338 |
| Other | : N/A |
| ISRCTN | ISRCTN54371254 |