Patients with Crohn's disease who have not responded to immunosupressant medication
Conditions
Interventions
Product Name: Cyclophosphamide
Product Code: N/A
Pharmaceutical Form: Intravenous infusion
INN or Proposed INN: cyclophosphamide
CAS Number: N/A
Current Sponsor code: N/A
Other descriptive name: N/A
C
Sponsors
European Group for Blood and Marrow Transplantation (EMBT)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria for patients: mandatory 1) Age between 18 and 50 years a) Patients aged 50-65 can participate if specially approved by the Trial Steering Committee 2) Confirmed diagnosis of active Crohn’s Disease: a) Diagnosis of Crohn’s disease based on typical radiological appearances and / or typical histology b) Active disease at the time of randomisation defined as i) Crohn’s disease activity index (CDAI) equal to or more than 250 at any time within 3 months prior to trial entry and equal to or more than 2 of the following: ii) raised CRP, iii) endoscopic evidence of active disease confirmed on histology iv) clear evidence of active small bowel Crohn’s disease on small bowel barium study. 3) Unsatisfactory course despite 3 immunosuppressive agents (usually azathioprine, methotrexate and infliximab) in addition to corticosteroids. Patients should have relapsing disease (ie equal to or more than 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: a) IBDQ b) European Questionnaire of Lifequality (EuroQOL–5D) c) SF-36 d) Impaired function on Karnofsky index 5) Current problems unsuitable for surgery and patient at risk for developing short bowel syndrome. 6) Informed consent a) Prepared to enter controlled study. b) Prepared to undergo additional study procedures as per trial schedule c) Patient has undergone intensive counselling about risks d) Consent to future genotyping assessments is optional, but is not required for the patient to enter the trial Inclusion criteria for patients: discretionary 1. Wherever possible, diseased tissue should be accessible endoscopically for objective histological study a. 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 2. Smokers may enter the study provided they have received intensive counselling about smoking. 3. Patients with an ileostomy or colostomy may enter the study. Clinical activity should be assessed using modified CDAI and Harvey Bradshaw scoring method. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion criteria for patients 1) Pregnancy or unwillingness to use adequate contraception during the study 2) Concomitant severe disease a) renal: creatinine clearance 6.7 kpa. Patients not known to have respiratory disease need not have blood gas measurements. i) 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 a) Current abscess or significant active infection. b) Perianal sepsis is not an exclusion provided there is natural free drainage or a Seton suture(s) have been placed. c) History of tuberculosis or at current increased risk of tuberculosis d) Mantoux test result or other investigations that the investigator or Steering Committee regard as evidence of active tuberculosis. e) Abnormal chest x ray (CXR) consistent with active infection or neoplasm. 4) Significant malnutrition: Body Mass Index (BMI) = 18, serum albumin = 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the potential clinical benefit of hematopoietic stem cell (HSC) 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 Objective: 1) to evaluate the safety of hematopoietic stem cell transplantatation (HSCT) in Crohn's disease patients who have not responded to immunosupressant medication 2) To evaluate the impact of HSCT on health related and generic quality of life measures 3) To identify factors predictive of success;Primary end point(s): The primary endpoint will be the proportion of patients in sustained disease remission at one year. Sustained disease remission, based upon European Crohn's and Colitis Organisation consensus is defined as: A minimum of a 3 month period of Crohn’s disease activity index (CDAI) = 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. | — |
Countries
United Kingdom
Outcome results
None listed