Crohn Disease
Conditions
Keywords
Crohn's Disease, HSCT, Autologous, EBMT, ECCO
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.
Interventions
PROCEDUREAutologous haematopoietic stem cell transplant
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.
Sponsors
The Broad Foundation
European Society for Blood and Marrow Transplantation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Impact of HSCT on health related, and generic, quality of life measures | 1 - 2 Years | To evaluate the impact of HSCT on health related, and generic, quality of life measures |
| To identify factors predictive of success | 1-2 years | To identify factors predictive of success |
Countries
Belgium, Canada, France, Italy, Spain, Switzerland, United Kingdom
Outcome results
None listed