Condition category
Musculoskeletal Diseases
Date applied
21/09/2005
Date assigned
19/10/2005
Last edited
25/07/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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

http://www.ebmt.org

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

  1. 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.

  2. 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.

Additional files

Editorial Notes