A randomised controlled trial to assess the safety and effectiveness of stem cell transplantation using a reduced intensity regimen in patients with treatment resistant Crohn’s disease

Phase 3

Completed

• Conditions: Refractory Crohn's disease; Digestive System; Crohn's disease

• Registration Number: ISRCTN17160440
• Lead Sponsor: Barts Health NHS Trust

Brief Summary

2019 Protocol article in https://pubmed.ncbi.nlm.nih.gov/31151436/ (added 11/08/2022) 2024 Results article in https://doi.org/10.1016/s2468-1253(23)00460-0 (added 12/02/2024)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-10-31
• Study Completion: 2021-11-30
• Last Update Posted: 27 February 2024

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

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

Exclusion Criteria

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) until at least 12 months after the last dose of study drug.
12. Contraindication to the use of cyclophosphamide, fludarabine, filgrastim or rabbit ATG.
13. Participants with significant medical co-morbidity that precludes HSCT adjudicated by the TMG.
14. Participants with significant psychiatric co-morbidity.
15. Significant language barriers, which are likely to affect the participant’s understanding of the study, or ability to complete outcome questionnaires.
16. Concurrent participation in another interventional clinical trial.
17. Participants who are not considered medically fit for HSCT defined by any of the following:
17.1. Renal: creatinine clearance <40 ml/min (measured or estimated)
17.2. 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
17.3. Hepatic: AST > two times the upper limit of normal
17.4. Concurrent neoplasms or myelodysplasia
17.5. Bone marrow insufficiency defined as neutropenia with an absolute neutrophil count <1x10(9)/l, or thrombocytopenia with a platelet count <50x10(9)/l, or anaemia with a haemoglobin <80 g/l
17.6. Uncontrolled hypertension, defined as resting systolic blood pressure >= 140 and/or resting diastolic pressure >= 90 mmHg despite at least 2 anti-hypertensive agents (subject to discussion at TMG).
17.7. 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.
17.8. 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 <8 kPa or carbon dioxide tension >6.7 kPa. FEV1/FVC <50%. Patients not known to have respiratory disease need not have blood gas measurements.

Study & Design

• Study Type: Interventional
• Study Design: Not specified