Contact information
Type
Scientific
Primary contact
Prof Jacob M. van Laar
ORCID ID
Contact details
Institute of Cellular Medicine
Newcastle University
Newcastle upon Tyne
NE2 4HH
United Kingdom
+44 (0)191 222 7139
j.m.van-laar@ncl.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
NTR338
Study information
Scientific title
High dose immunoablation and autologous haematopoietic stem cell transplantation versus monthly intravenous pulse therapy
Acronym
ASTIS
Study hypothesis
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
Ethics approval received from the local medical ethics committee
Study design
Multicentre randomised active-controlled parallel-group trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
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 names
Cyclophosphamide, filgrastim, rabbit Anti-Thymocyte Globulin (rbATG)
Primary outcome measures
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.
Secondary outcome measures
Key secondary outcomes include:
1. Treatment related mortality
2. Treatment toxicity
3. Progression-free survival
Overall trial start date
22/03/2001
Overall trial end date
01/01/2008
Reason abandoned
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
156
Participant exclusion criteria
Patients with concomitant severe disease, extensive pretreatment according to predefined criteria with cyclophosphamide are excluded.
Recruitment start date
22/03/2001
Recruitment end date
01/01/2008
Locations
Countries of recruitment
Austria, Belgium, Canada, France, Germany, Greece, Italy, Netherlands, Switzerland, United Kingdom
Trial participating centre
Institute of Cellular Medicine,
Newcastle upon Tyne
NE2 4HH
United Kingdom
Sponsor information
Organisation
European Group for Bone Marrow Transplantation
Sponsor details
EBMT Central Office
Dept. Haematology
MacDonald Buchanan Building
Middlesex Hospital
Mortimer Street
London
W1N 8AA
United Kingdom
+44 (0)20 7380 9317
l.clark@ucl.ac.uk
Sponsor type
Other
Website
Funders
Funder type
Industry
Funder name
European League Against Rheumatism (EULAR)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Amgen Europe
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Sangstat B.V. (The Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Horton Foundation (Switzerland)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
AP - HP
Alternative name(s)
Assistance Publique Hôpitaux de Paris, AP-HP
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
France
Funder name
European Group for Blood and Marrow Transplantation (EBMT)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
2005 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/16162905
2012 results in: http://abstracts.hematologylibrary.org/cgi/content/abstract/120/21/964
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/25058083
Publication citations
-
Protocol
van Laar JM, Farge D, Tyndall A, Autologous Stem cell Transplantation International Scleroderma (ASTIS) trial: hope on the horizon for patients with severe systemic sclerosis., Ann. Rheum. Dis., 2005, 64, 10, 1515, doi: 10.1136/ard.2005.043240.
-
Results
van Laar JM, Farge D, Sont JK, Naraghi K, Marjanovic Z, Larghero J, Schuerwegh AJ, Marijt EW, Vonk MC, Schattenberg AV, Matucci-Cerinic M, Voskuyl AE, van de Loosdrecht AA, Daikeler T, Kötter I, Schmalzing M, Martin T, Lioure B, Weiner SM, Kreuter A, Deligny C, Durand JM, Emery P, Machold KP, Sarrot-Reynauld F, Warnatz K, Adoue DF, Constans J, Tony HP, Del Papa N, Fassas A, Himsel A, Launay D, Lo Monaco A, Philippe P, Quéré I, Rich É, Westhovens R, Griffiths B, Saccardi R, van den Hoogen FH, Fibbe WE, Socié G, Gratwohl A, Tyndall A, , Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial., JAMA, 2014, 311, 24, 2490-2498, doi: 10.1001/jama.2014.6368.