ASTIC Autologous Stem Cell Transplantation for Crohn's Disease

NCT00297193 | Terminated Phase 3 DMC

• 2 other identifiers: EudraCT2005-003337-40ASTIC
• Study Type: interventional
• Target: 45
• Locations: 7 countries
• Sites: 19

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.

Conditions

Crohn Disease

Keywords

Crohn's Disease; HSCT; Autologous; EBMT; ECCO

Outcome Measures

Primary Outcomes (1)

• Proportion patients in sustained disease remission

  To evaluate the 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 in patients with Crohn' s disease.

  1 year

Secondary Outcomes (1)

• patients who have not responded to immunosuppressant medication

  1 - 2 years

Other Outcomes (2)

• Impact of HSCT on health related, and generic, quality of life measures

  1 - 2 Years

• To identify factors predictive of success

  1-2 years

Study Arms (2)

Transplant Arm

EXPERIMENTAL

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

Procedure: Autologous haematopoietic stem cell transplant

Delayed Transplant

EXPERIMENTAL

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

Procedure: Autologous haematopoietic stem cell transplant

Interventions

Autologous haematopoietic stem cell transplant PROCEDURE

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.

Delayed Transplant; Transplant Arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 50 years (Patients aged 50-65 can participate if specially approved by the Trial Steering Committee)
• Confirmed diagnosis of active Crohn's Disease
• 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.
• Impaired function and quality of life, compared to population means, on at least one of the following:
• IBDQ (Appendix 6)
• European Questionnaire of Life quality (EuroQOL-5D, Appendix 4)
• Impaired function on Karnofsky index (Appendix 7)
• Current problems unsuitable for surgery and patient at risk for developing short bowel syndrome.
• Informed consent
• 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.
• Smokers may enter the study provided they have received intensive counselling about smoking.
• Add patients with ileostomy/colostomy and patients with short bowel syndrome

You may not qualify if:

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

Sponsors & Collaborators

• European Society for Blood and Marrow Transplantation: lead
• The Broad Foundation: collaborator

Study Sites (19)

University Hospital Gasthuisberg

Leuven, Herestraat 49, 3000, Belgium

Location

University of Calgery

Calgary, Alberta, T2N 2T9, Canada

Location

Hopital Huriez Chru

Lille, 59037, France

Location

Hospital Sanin-Louis

Paris, 75010, France

Location

Dipatimento di Medicina Interna E Gastroenterologia

Bologna, 40138, Italy

Location

Universita di Bologna Interna e Gastroenterologia Policlinico Saint Orsola

Bologna, 40138, Italy

Location

Careggi Hospital

Florence, 50134, Italy

Location

Istituto Clinico Humanitas

Milan, 20089, Italy

Location

Fondazione IRCCS Ospedale Maggiore Policlinico Mangiagalli e Regina Elena

Milan, 20122, Italy

Location

L Sacco University Hopsital

Milan, 20157, Italy

Location

Casa Sollievo Della Sofferenza IRCCS Hospital

San Giovanni Rotondo, 71013, Italy

Location

Hospital Universitari Germans Trias I Pujol, Dept of Gastroenterology

Badalona, 08916, Spain

Location

University Hospital

Basel, CH-4031, Switzerland

Location

Universitätsspital Zürich

Zurich, 8091, Switzerland

Location

The John Radcliffe Hospital

Oxford, Headington, OX3 9DU, United Kingdom

Location

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

Barts and the London NHS Trust

London, E1 1BB, United Kingdom

Location

City Hospital

Nottingham, NG5 1PB, United Kingdom

Location

Nottingham Digestive Diseases Centre

Nottingham, NG7 2UH, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 28497755 DERIVED

• 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.

  PMID: 26670970 DERIVED

MeSH Terms

Conditions

Crohn Disease

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• Christopher J Hawkey

  Nottingham University Hospital - Wolfson Digestive Diseases Centre

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2006
• First Posted: February 28, 2006
• Study Start: June 1, 2006
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2017
• Last Updated: December 22, 2020

Record last verified: 2013-08

Locations

GB (5); CA (1); FR (2); IT (7); BE (1); ES (1); CH (2)