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ISRCTN
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ISRCTN54371254
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ClinicalTrials.gov identifier
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Public title
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Autologous Stem cell Transplantation International Scleroderma (ASTIS) Trial
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Scientific title
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High dose immunoablation and autologous haematopoietic stem cell transplantation versus monthly intravenous pulse therapy
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Acronym
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ASTIS trial
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Serial number at source
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NTR338
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Study hypothesis
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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.
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Lay summary
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Ethics approval
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Ethics approval received from the local medical ethics committee
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Study design
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Multicentre, randomised, active controlled, parallel group trial
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Countries of recruitment
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Australia, Austria, Canada, France, Germany, Greece, Italy, Netherlands, Switzerland, United Kingdom
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Disease/condition/study domain
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Systemic sclerosis
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Participants - inclusion criteria
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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
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Participants - exclusion criteria
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Patients with concomitant severe disease, extensive pretreatment according to predefined criteria with cyclophosphamide are excluded.
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Anticipated start date
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22/03/2001
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Anticipated end date
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01/01/2008
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Status of trial
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Completed |
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Patient information material
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Target number of participants
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200
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Interventions
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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).
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Primary outcome measure(s)
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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.
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Secondary outcome measure(s)
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Key secondary outcomes include:
1. Treatment related mortality
2. Treatment toxicity
3. Progression-free survival
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Sources of funding
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1. European League Against Rheumatism (EULAR)
2. Amgen Europe
3. Sangstat B.V. (The Netherlands)
4. Horton Foundation (Switzerland)
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Trial website
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http://www.astistrial.com
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Publications
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Results in http://www.ncbi.nlm.nih.gov/pubmed/16162905
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Contact name
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Dr
Jacob
van Laar
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Address
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Dept. of Rheumatology B2-17
Leiden University Medical Center
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City/town
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Leiden
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Zip/Postcode
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2333 ZA
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Country
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Netherlands
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Tel
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+31 (0)71 5263598
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Fax
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+31 (0)71 5266752
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Email
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j.m.van_laar@lumc.nl
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Sponsor
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European Group Bone Marrow + Transplantation (EBMT)/European League Against Rheumatism (EULAR) Working Party Autoimmune Diseases
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Address
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EBMT Central Office
Dept. Haematology
MacDonald Buchanan Building
Middlesex Hospital
Mortimer Street
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City/town
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London
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Zip/Postcode
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W1N 8AA
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Country
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United Kingdom
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Tel
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+44 (0)20 7380 9317
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Fax
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+44 (0)20 7580 7536
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Email
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k.champion@ucl.ac.uk
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Sponsor website:
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http://www.ebmt.org
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Date applied
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21/09/2005
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Last edited
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10/09/2008
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Date ISRCTN assigned
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19/10/2005
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