Autologous Stem cell Transplantation International Crohn's disease trial

Completed

• Conditions: Topic: Oral and Gastrointestinal; Subtopic: Oral and Gastrointestinal (all Subtopics); Disease: Gastrointestinal; Digestive System; Crohn's disease

• Registration Number: ISRCTN39133198
• Lead Sponsor: European Group for Blood and Marrow Transplantation (EBMT) (UK)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-05-21
• Last Update Posted: 17 October 2016

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

Mandatory:
1. Aged between 18 and 50 years (patients aged 50 - 65 years can participate if specially approved by the Trial Steering Committee)
2. Confirmed diagnosis of active Crohn's Disease:
2.1. Diagnosis of Crohn's disease based on typical radiological appearances and/or typical histology
2.2. Active disease at the time of registration to the trial, defined as Crohn's Disease Activity Index (CDAI) greater than or equal to 250 at any time within 3 months prior to trial entry, and greater than two of the following:
2.2.1. Raised C-reactive protein (CRP)
2.2.2. Endoscopic evidence of active disease confirmed on histology
2.2.3. Clear evidence of active small bowel Crohn's disease on small bowel barium study
3. Unsatisfactory course despite three immunosuppressive agents (usually azathioprine, methotrexate and infliximab) in addition to corticosteroids. Patients should have relapsing disease (i.e. greater than or equal to 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:
4.1. Inflammatory Bowel Disease Questionnaire (IBDQ)
4.2. European Questionnaire of Life Quality (EuroQol-5D)
4.3. Impaired function on Karnofsky Index
5. Current problems unsuitable for surgery and patient at risk for developing short bowel syndrome
6. Informed consent

Discretionary:
7. Wherever possible, diseased tissue should be accessible endoscopically for objective histological study
8. Small bowel disease that is extensive but does not extend to duodenum or terminal ileum is an exception, which will allow participation without endoscopy of diseased areas. All patients will however undergo flexible sigmoidoscopy.
9. Smokers may enter the study provided they have received intensive counselling about smoking
10. Patients with an ileostomy or colostomy may enter the study. Clinical activity should be assessed using modified CDAI and Harvey Bradshaw scoring method

Exclusion Criteria

1. Pregnancy or unwillingness to use adequate contraception during the study, if a woman of childbearing age
2. Concomitant severe disease:
2.1. Renal: creatinine clearance less than 40 ml/min (measured or estimated)
2.2. Cardiac: clinical evidence of refractory congestive heart failure; left ventricular ejection fraction less than 45% by multigated radionuclide angiography (MUGA) or cardiac echo; chronic atrial fibrillation necessitating oral anticoagulation; uncontrolled ventricular arrhythmia; pericardial effusion with hemodynamic consequences as evaluated by an experienced echo cardiographer
2.3. Psychiatric disorders including active drug or alcohol abuse
2.4. Concurrent neoplasms or myelodysplasia
2.5. Bone marrow insufficiency defined as leucocytopaenia less than 3.0 x 10^9/l, thrombocytopenia less than 50 x 10^9/l, anaemia less than 8 g/dl, CD4+ T lymphopenia less than 200 x 10^6/l
2.6. Uncontrolled hypertension, defined as resting systolic blood pressure greater than or equal to 140 ml and/or resting diastolic pressure greater than or equal to 90 ml mercury despite at least two anti-hypertensive agents
2.7. Uncontrolled acute or chronic infection with human immunodeficiency virus (HIV), Human T-lymphotropic virus (HTLV) - 1 or 2, hepatitis viruses or any other infection the investigator or Steering Committee consider a contraindication to participation
2.8. Other chronic disease causing significant organ failure, including established cirrhosis with evidence of impaired synthetic function on biochemical testing and known respiratory disease causing resting arterial oxygen tension less than 8 kpa or carbon dioxide tension greater than 6.7 kpa. Patients not known to have respiratory disease need not have blood gas measurements.
2.9. Crohn's Disease symptoms predominantly due to fibrotic stricturing and unlikely to respond to immune manipulation, in the opinion of any of the investigators or the steering committee
3. Infection or risk thereof:
3.1. Current abscess or significant active infection
3.2. Perianal sepsis is not an exclusion provided there is natural free drainage or a Seton suture(s) have been placed
3.3. History of tuberculosis or at current increased risk of tuberculosis
3.4. Mantoux test result or other investigations that the investigator or Steering Committee regard as evidence of active tuberculosis
3.5. Abnormal chest x ray (CXR) consistent with active infection or neoplasm
4. Significant malnutrition: body mass index (BMI) less than or equal to 18, serum albumin less than 20 g/l
5. Previous poor compliance
6. Concurrent enrolment in any other protocol using an investigational drug or hematopoietic growth factor up to four weeks before study entry
7. Lack of funding

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Proportion of patients in sustained disease remission at one year. Sustained disease remission, based upon ECCO consensus is defined as: A minimum of a 3 month period of Crohn's disease activity index (CDAI) less than 150 without steroids or immunosuppressive drugs and no mucosal erosion or ulceration at ileocolonoscopy and no definite evidence of small bowel Crohn's Disease on barium studies.