Clinical trial NCT00297193: ASTIC Autologous Stem Cell Transplantation for Crohn's Disease
Official title: Autologous Stem Cell Transplantation for Crohn's Disease: ASTIC
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Crohn Disease
Keywords: Crohn's Disease
HSCT
Autologous
EBMT
ECCO
Lead sponsor: European Society for Blood and Marrow Transplantation
Sponsor class: NETWORK
Collaborators: name: The Broad Foundation
First posted: 2006-02-28
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Transplant study for patients with relapsing Crohn's disease demonstrating clear intolerance or toxicity to conventional treatment.

The purpose of this study is to determine whether there is a potential clinical benefit of hematopoietic stem cell mobilisation followed by high dose immuno-ablation and autologous stem cell transplantation versus hematopoietic stem cell mobilisation only followed by best clinical practice.

Detailed description: Open label, phase III, randomised, multicentre study comparing early transplantation procedure with transplantation carried out to the same protocol but delayed by one year. The status of patients undergoing early HSCT will be evaluated after one year and compared to those about to undergo delayed HSCT

Patients will be randomised to:

* Hematopoietic stem cell mobilisation followed, within 4 weeks, by high dose immunoablation and autologous stem cell transplantation
* Hematopoietic stem cell mobilisation followed, after 59 weeks, by high dose immunoablation and autologous hematopoietic stem cell transplantation

All patients will be mobilised prior to randomisation. Those receiving early transplantation will be compared over the first year with those whose transplant has been delayed.

Eligibility criteria: Inclusion Criteria:

Inclusion criteria: mandatory

1. Age between 18 and 50 years (Patients aged 50-65 can participate if specially approved by the Trial Steering Committee)
2. Confirmed diagnosis of active Crohn's Disease
3. Unsatisfactory course despite 3 immunosuppressive agents (usually azathioprine, methotrexate and infliximab) in addition to corticosteroids. Patients should have relapsing disease (i.e. \>1 exacerbation/year) despite thiopurines, methotrexate and/or infliximab maintenance therapy or clear demonstration of intolerance / toxicity to these drugs.
4. Impaired function and quality of life, compared to population means, on at least one of the following:

   1. IBDQ (Appendix 6)
   2. European Questionnaire of Life quality (EuroQOL-5D, Appendix 4)
   3. Impaired function on Karnofsky index (Appendix 7)
5. Current problems unsuitable for surgery and patient at risk for developing short bowel syndrome.
6. Informed consent

Inclusion criteria: discretionary

1. Wherever possible, diseased tissue should be accessible endoscopically for objective histological study but in the case of small bowel disease that is extensive but does not extend to duodenum or terminal ileum, participation without endoscopy is allowed.
2. Smokers may enter the study provided they have received intensive counselling about smoking.
3. Add patients with ileostomy/colostomy and patients with short bowel syndrome

Exclusion Criteria:

1. Pregnancy or unwillingness to use adequate contraception during the study
2. Concomitant severe disease
3. Diarrhoea due to short small or large bowel
4. Infection or risk thereof
5. Significant malnutrition: Body Mass Index (BMI) ≤18, serum albumin \<20 g/l
6. Previous poor compliance
7. Concurrent enrolment in any other protocol using an investigational drug or hematopoietic growth factor up to four weeks before study entry.
8. Lack of funding

Primary outcomes:
measure: Proportion patients in sustained disease remission
timeFrame: 1 year
Secondary outcomes:
measure: patients who have not responded to immunosuppressant medication
timeFrame: 1 - 2 years
Other outcomes:
measure: Impact of HSCT on health related, and generic, quality of life measures
timeFrame: 1 - 2 Years
measure: To identify factors predictive of success
timeFrame: 1-2 years
Locations:
city: Leuven
country: Belgium
facility: University Hospital Gasthuisberg
state: Herestraat 49
city: Calgary
country: Canada
facility: University of Calgery
state: Alberta
city: Lille
country: France
facility: Hopital Huriez Chru
city: Paris
country: France
facility: Hospital Sanin-Louis
city: Bologna
country: Italy
facility: Dipatimento di Medicina Interna E Gastroenterologia
city: Bologna
country: Italy
facility: Universita di Bologna Interna e Gastroenterologia Policlinico Saint Orsola
city: Florence
country: Italy
facility: Careggi Hospital
city: Milan
country: Italy
facility: Istituto Clinico Humanitas
city: Milan
country: Italy
facility: Fondazione IRCCS Ospedale Maggiore Policlinico Mangiagalli e Regina Elena
city: Milan
country: Italy
facility: L Sacco University Hopsital
city: San Giovanni Rotondo
country: Italy
facility: Casa Sollievo Della Sofferenza IRCCS Hospital
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias I Pujol, Dept of Gastroenterology
city: Basel
country: Switzerland
facility: University Hospital
city: Zürich
country: Switzerland
facility: Universitätsspital Zürich
city: Oxford
country: United Kingdom
facility: The John Radcliffe Hospital
state: Headington
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: London
country: United Kingdom
facility: Barts and the London NHS Trust
city: Nottingham
country: United Kingdom
facility: City Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham Digestive Diseases Centre
Study officials:
affiliation: Nottingham University Hospital - Wolfson Digestive Diseases Centre
name: Christopher J Hawkey
role: STUDY_CHAIR
References:
citation: Lindsay JO, Allez M, Clark M, Labopin M, Ricart E, Rogler G, Rovira M, Satsangi J, Farge D, Hawkey CJ; ASTIC trial group; European Society for Blood and Marrow Transplantation Autoimmune Disease Working Party; European Crohn's and Colitis Organisation. Autologous stem-cell transplantation in treatment-refractory Crohn's disease: an analysis of pooled data from the ASTIC trial. Lancet Gastroenterol Hepatol. 2017 Jun;2(6):399-406. doi: 10.1016/S2468-1253(17)30056-0. Epub 2017 Apr 6.
citation: Hawkey CJ, Allez M, Clark MM, Labopin M, Lindsay JO, Ricart E, Rogler G, Rovira M, Satsangi J, Danese S, Russell N, Gribben J, Johnson P, Larghero J, Thieblemont C, Ardizzone S, Dierickx D, Ibatici A, Littlewood T, Onida F, Schanz U, Vermeire S, Colombel JF, Jouet JP, Clark E, Saccardi R, Tyndall A, Travis S, Farge D. Autologous Hematopoetic Stem Cell Transplantation for Refractory Crohn Disease: A Randomized Clinical Trial. JAMA. 2015 Dec 15;314(23):2524-34. doi: 10.1001/jama.2015.16700.