ASTIC Autologous Stem Cell Transplantation for Crohn's Disease

Study Overview
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Brief Summary
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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
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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.

Official Title
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Autologous Stem Cell Transplantation for Crohn's Disease: ASTIC

Conditions
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Crohn Disease

Intervention / Treatment
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* Procedure: Autologous haematopoietic stem cell transplant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria: mandatory 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 Inclusion criteria: discretionary 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transplant Arm<br>Hematopoietic stem cell mobilisation followed, within 4 weeks, by high dose immunoablation and autologous stem cell transplantation | Procedure: Autologous haematopoietic stem cell transplant<br>* 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.<br>|
| Experimental: Delayed Transplant<br>Hematopoietic stem cell mobilisation followed, after 59 weeks, by high dose immunoablation and autologous hematopoietic stem cell transplantation | Procedure: Autologous haematopoietic stem cell transplant<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's Disease, HSCT, Autologous, EBMT, ECCO