ASTIC Autologous Stem Cell Transplantation for Crohn's Disease

Phase 3

Terminated

• Conditions: Crohn Disease
• Interventions: Procedure: Autologous haematopoietic stem cell transplant

• Registration Number: NCT00297193
• Lead Sponsor: European Society for Blood and Marrow Transplantation

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.

Study Timeline

• Study First Submitted: 2006-02-27
• Study First Submitted QC: 2006-02-27
• Study First Posted: 2006-02-28
• Study Start: 2006-06
• Primary Completion: 2013-03
• Status Verified: 2013-08
• Study Completion: 2017-03
• Last Update Submitted: 2020-12-21
• Last Update Posted: 2020-12-22

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 45

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Delayed Transplant	Autologous haematopoietic stem cell transplant	Hematopoietic stem cell mobilisation followed, after 59 weeks, by high dose immunoablation and autologous hematopoietic stem cell transplantation
Transplant Arm	Autologous haematopoietic stem cell transplant	Hematopoietic stem cell mobilisation followed, within 4 weeks, by high dose immunoablation and autologous stem cell transplantation

Primary Outcome Measures

Name	Time	Method
Proportion patients in sustained disease remission	1 year	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.

Secondary Outcome Measures

Name	Time	Method
patients who have not responded to immunosuppressant medication	1 - 2 years	To evaluate the safety of Hematopoietic Stem Cell Transplantation (HSCT) in Crohn's disease patients who have not responded to immunosuppressant medication

Trial Locations

Locations (19)

University Hospital Gasthuisberg; 🇧🇪 Leuven, Herestraat 49, Belgium

University of Calgery; 🇨🇦 Calgary, Alberta, Canada

Hopital Huriez Chru; 🇫🇷 Lille, France

Hospital Sanin-Louis; 🇫🇷 Paris, France

Careggi Hospital; 🇮🇹 Florence, Italy

Fondazione IRCCS Ospedale Maggiore Policlinico Mangiagalli e Regina Elena; 🇮🇹 Milan, Italy

L Sacco University Hopsital; 🇮🇹 Milan, Italy

Hospital Universitari Germans Trias I Pujol, Dept of Gastroenterology; 🇪🇸 Badalona, Spain

Universitätsspital Zürich; 🇨🇭 Zürich, Switzerland

The John Radcliffe Hospital; 🇬🇧 Oxford, Headington, United Kingdom

Western General Hospital; 🇬🇧 Edinburgh, United Kingdom

Nottingham Digestive Diseases Centre; 🇬🇧 Nottingham, United Kingdom

Barts and the London NHS Trust; 🇬🇧 London, United Kingdom

City Hospital; 🇬🇧 Nottingham, United Kingdom

Dipatimento di Medicina Interna E Gastroenterologia; 🇮🇹 Bologna, Italy

Universita di Bologna Interna e Gastroenterologia Policlinico Saint Orsola; 🇮🇹 Bologna, Italy

Istituto Clinico Humanitas; 🇮🇹 Milan, Italy

Casa Sollievo Della Sofferenza IRCCS Hospital; 🇮🇹 San Giovanni Rotondo, Italy

University Hospital; 🇨🇭 Basel, Switzerland