Controlled trial to assess low intensity autologous stem cell transplant in refractory Crohn's Disease

Phase 1

• Conditions: Refractory Crohn's Disease; MedDRA version: 20.0Level: PTClassification code 10011401Term: Crohn's diseaseSystem Organ Class: 10017947 - Gastrointestinal disorders; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2017-002545-30-GB
• Lead Sponsor: Barts Health NHS Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-06-07
• Last Update Posted: 5 January 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 99

Inclusion Criteria

A participant is eligible for the study if the following criteria are met:
1.Participant of any gender, aged between 18 – 60
2.Participants must be willing and able to provide full informed consent.
3.Participants should be well nourished and of healthy weight in the opinion of the PI (typically BMI >18.5).
4.Diagnosis of CD using colonoscopy, histology and/or radiology.
5.Disease duration of at least six months.
6.Disease distribution accessible to endoscopic assessment (ileal, ileo-caecal, or colonic).
7.Active clinical CD activity with impaired quality of life at any time within 3 months prior to randomisation into the trial, as assessed by a gastroenterology clinician.
8.Participants will be refractory or intolerant to azathioprine, mercaptopurine or methotrexate.
9.Participants will be refractory or intolerant to at least two classes of biologic therapy (currently anti-TNF therapy, Vedolizumab or Ustekinumab) despite dose optimisation.
10.Participants where surgery is considered not appropriate or has been declined.
11.Endoscopic evidence of active disease in screening (SES CD ulceration sub-score of 2 or more in at least one segment).
12.Satisfactory EBMT Autoimmune Disease Working Party (ADWP) recommended screening assessment prior to HSCT.
13.Willingness to discontinue all immunosuppressant medication after randomisation if allocated to HSCT arm.
14.Participants, who, in the opinion of the TMG, are fit enough to undergo treatment.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 99
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

A participant is not eligible for the study if any of the following criteria are met:
1.Diagnosis of ulcerative colitis or indeterminate colitis.
2.No evidence of active CD on screening ileocolonoscopy.
3.Inability to assess for active disease at ileocolonoscopy due to strictures.
4.Undrained perianal fistulae (patients with previous perianal disease or perianal disease adequately drained with a seton in situ are eligible).
5.Presence of undrained perianal sepsis on screening pelvic MRI.
6.Evidence of intra-abdominal sepsis on abdominal MRI.
7.Active or latent mycobacterial infection.
8.Prior exposure to Hepatitis B, Hepatitis C or HIV.
9.Evidence of an enteric or systemic infection.
10.Participant is currently pregnant or breastfeeding, or planning pregnancy within the study duration. Current pregnancy will be confirmed with a pregnancy test at screening assessment.
11.Unwilling to use adequate contraception (if appropriate) during duration of 48 week follow up.
12.Participants with significant medical co-morbidity that precludes HSCT adjudicated by the TMG.
13.Participants with significant psychiatric co-morbidity.
14.Significant language barriers, which are likely to affect the participant’s understanding of the study, or ability to complete outcome questionnaires.
15.Concurrent participation in another interventional clinical trial.
16.Participants who are not considered medically fit for HSCT defined by any of the following. Participants who meet one or more of the below criteria, who, in the opinion of the local investigator are medically fit, may be discussed at TMG for potential inclusion, and this will be documented in the patient’s notes, and the site file:
a.Renal: creatinine clearance <40ml/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; uncontrolled ventricular arrhythmia; pericardial effusion with haemodynamic consequences as evaluated by an experienced echo cardiographer
c.Hepatic: AST > two times the upper limit of normal
d.Concurrent neoplasms or myelodysplasia
e.Bone marrow insufficiency defined as neutropenia with an absolute neutrophil count <1x109/l, or thrombocytopenia with a platelet count <50x109/l, or anaemia with a haemoglobin <80g/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 (subject to discussion at TMG).
g.Uncontrolled acute or chronic infection with HIV, HTLV – 1 or 2, hepatitis viruses or any other infection the investigator or TMG 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 <8kPa or carbon dioxide tension >6.7kPa. FEV1/FVC <50%. Patients not known to have respiratory disease need not have blood gas measurements.

Study & Design

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