Refractory Crohn's disease Digestive System Crohn's disease
Conditions
Interventions
Following consent, and confirmation of eligibility, participants are randomised, using a web-based system to receive either the HSCTlite intervention, or standard care, in the ratio 2:1.
HSCTlite In
Sponsors
Barts Health NHS Trust
Eligibility
Sex/Gender
All
Inclusion criteria
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
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 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 = 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 6.7 kPa. FEV1/FVC <50%. Patients not known to have respiratory disease need not have blood gas measurements.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Regression of mucosal ulceration is assessed using the SES-CD ulcer sub score on colonoscopy at week 48. | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 15/03/2018: Clinical secondary outcome measures: 1. Clinical remission is measured using the Crohn’s Disease Activity Index (CDAI) at baseline, week 8, week 14, week 24, week 32, week 40 and week 48 2. Steroid free clinical remission is measured using the CDAI at baseline, week 8, week 14, week 24, week 32, week 40 and week 48 3. Clinical remission is measured using the Harvey Bradshaw Index (HBI) at baseline, week 8, week 14, week 24, week 32, week 40 and week 48 4. Clinical remission is measured using the PRO2 at baseline, week 8, week 14, week 24, week 32, week 40 and week 48 5. Absolute Crohn’s Disease activity is measured using the CDAI at baseline and week 48 6. Endoscopic ulceration is measured using the SES-CD at baseline and week 48 7. Change in CDAI score is measured between baseline and week 48 8. Change in SES-CD score is measured between baseline and week 48 9. Complete endoscopic remission is measured using the SES-CD at baseline and week 48 Safety secondary outcome measures: 1. Toxicity of chemotherapy is measured using NCI CTCAE grading of adverse events at week 4, week 8, week 14, week 24, week 32, week 40 and week 48 2. Adverse events are measured through documentation of adverse events at week 4, week 8, week 14, week 24, week 32, week 40 and week 48 Patient-reported secondary outcome measures: 1. Crohn’s disease specific quality of life is measured using the IBDQ at baseline, week 8, week 14, week 24, week 32, week 40 and week 48 2. Crohn’s disease specific quality of life is measured using the IBD Control questionnaire at baseline, week 8, week 14, week 24, week 32, week 40 and week 48 3. Quality of life is measured using the EQ-5D-5L at baseline, week 8, week 14, week 24, week 32, week 40 and week 48 4. Healthcare resource use is measured using the healthcare resource utilisation questionnaire at baseline, week 8, week 14, week 24, week 32, week 40 and week 48 Exploratory secondary outcome measures: 1 | — |
Countries
England, Scotland, United Kingdom
Contacts
Public ContactLizzie Swaby
Outcome results
None listed