Autologous Stem Cell Transplantation for Crohn's Disease ('ASTIC'-Trial: Autologous Stem Cell Transplantation International Crohn's Disease Trial) - ASTIC

• Conditions: Patients with Crohn's disease who have not responded to immunosupressant medication

• Registration Number: EUCTR2005-003337-40-GB
• Lead Sponsor: European Group for Blood and Marrow Transplantation (EMBT)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-01-13
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 48

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 for patients

1)Pregnancy or unwillingness to use adequate contraception during the study

2)Concomitant severe disease
a)renal: creatinine clearance < 40 ml/min (measured or estimated)
b)cardiac: clinical evidence of refractory congestive heart failure; left ventricular ejection fraction < 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 echocardiographer
c)psychiatric disorders including active drug or alcohol abuse
d)concurrent neoplasms or myelodysplasia
e)bone marrow insufficiency defined as leucocytopenia <3.0 x 109/l, thrombocytopenia <50 x 109/l, anemia < 8 g/dl, CD4+ T lymphopenia < 200 x 106/l
f)uncontrolled hypertension, defined as resting systolic blood pressure = 140ml and/or resting diastolic pressure = 90ml mercury despite at least 2 anti-hypertensive agents.
g)Uncontrolled acute or chronic infection with HIV, HTLV – 1 or 2, hepatitis viruses or any other infection the investigator or Steering Committee consider a contraindication to participation.
h)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 <8 kpa or carbon dioxide tension >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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified