Autologous Stem cell Transplantation International Scleroderma (ASTIS) trial

ISRCTN	ISRCTN54371254
DOI	https://doi.org/10.1186/ISRCTN54371254
Protocol serial number	NTR338
Sponsor	European Group for Bone Marrow Transplantation
Funders	European League Against Rheumatism (EULAR), Amgen Europe, Sangstat B.V. (The Netherlands), Horton Foundation (Switzerland), AP - HP, European Group for Blood and Marrow Transplantation (EBMT)

Submission date: 21/09/2005
Registration date: 19/10/2005
Last edited: 25/07/2014

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Musculoskeletal Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Jacob M. van Laar
Scientific

Institute of Cellular Medicine
Newcastle University
Newcastle upon Tyne
NE2 4HH
United Kingdom

Phone	+44 (0)191 222 7139
Email	j.m.van-laar@ncl.ac.uk

Study information

Primary study design	Interventional
Study design	Multicentre randomised active-controlled parallel-group trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	High dose immunoablation and autologous haematopoietic stem cell transplantation versus monthly intravenous pulse therapy
Study acronym	ASTIS
Study objectives	It is postulated that high dose immunoablation and autologous stem cell transplantation has superior clinical benefit in comparison to intravenous pulse therapy cyclophosphamide, with respect to survival and prevention of major organ failure (referred to as event-free survival which is considered the primary endpoint) and has a greater impact on skin thickening, visceral involvement, functional status and quality of life. On 17/04/2012 the following changes were made to the trial record: 1. Australia has been removed from the countries of recruitment and Belgium added. 2. The target number of participants has been changed from 200 to 156.
Ethics approval(s)	Ethics approval received from the local medical ethics committee
Health condition(s) or problem(s) studied	Systemic sclerosis
Intervention	This multicentre prospective randomised controlled phase III study compares efficacy and safety of high dose immunoablation and autologous haematopoietic 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: 1. Mobilisation of haematopoietic stem cells with intravenous (IV) cyclophosphamide (2 x 2 g/m^2) and filgrastim (10 mg/kg/day) 2. Leukapheresis and selection of CD34+ stem cells 3. Conditioning with IV cyclophosphamide (200 mg/kg) and rbATG (7.5 mg/kg) 4. HSCT The procedures are normally completed within three to four months after randomisation. The control treatment arm consists of 12 consecutive monthly IV pulses cyclophosphamide (750 mg/m^2). As of 17/04/2012, the sponsor name has been amended from European Group Bone Marrow + Transplantation (EBMT)/European League Against Rheumatism (EULAR) Working Party Autoimmune Diseases to European Group for Bone Marrow Transplantation.
Intervention type	Drug
Phase	Phase III
Drug / device / biological / vaccine name(s)	Cyclophosphamide, filgrastim, rabbit Anti-Thymocyte Globulin (rbATG)
Primary outcome measure(s)	Current primary outcome measure(s) as of 29/05/2012 The primary endpoint is event-free survival defined as the time in days from the day of randomisation until the occurrence of death or the development of persistent major organ failure (heart, lung, kidney). Previous primary outcome measure(s) The primary endpoint is event-free survival defined as the time in days from the day of randomisation until the occurrence of death or the development of persistent major organ failure (heart, lung, kidney) during the study period of two years.
Key secondary outcome measure(s)	Key secondary outcomes include: 1. Treatment related mortality 2. Treatment toxicity 3. Progression-free survival
Completion date	01/01/2008

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	156
Key inclusion criteria	Patients with diffuse systemic sclerosis, aged 16 to 65 years, and: 1. Disease duration four years or less, plus evidence of heart, lung or kidney involvement, plus skin score of 15 or more, or 2. Disease duration two years or less, plus evidence of an acute phase reaction in blood, plus skin score 20 or more
Key exclusion criteria	Patients with concomitant severe disease, extensive pretreatment according to predefined criteria with cyclophosphamide are excluded.
Date of first enrolment	22/03/2001
Date of final enrolment	01/01/2008

Locations

Countries of recruitment

United Kingdom
England
Austria
Belgium
Canada
France
Germany
Greece
Italy
Netherlands
Switzerland

Study participating centre

Institute of Cellular Medicine,

Newcastle upon Tyne
NE2 4HH
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	25/06/2014		Yes	No
Protocol article	protocol	01/10/2005		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes