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BMC Gastroenterol. 2019 May 31;19(1):82. doi: 10.1186/s12876-019-0992-2.

Autologous stem cell transplantation in refractory Crohn's disease - low intensity therapy evaluation (ASTIClite): study protocols for a multicentre, randomised controlled trial and observational follow up study.

Author information

1
Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Sheffield, UK.
2
Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK.
3
Clinical Trials Research Unit, ScHARR, University of Sheffield, Sheffield, UK.
4
Clinical Trials Research Unit, ScHARR, University of Sheffield, Sheffield, UK. e.a.swaby@sheffield.ac.uk.
5
Department of Biostatistics & Health Informatics, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
6
European Society for Blood and Marrow Transplantation, Paris, France.
7
Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, UK.
8
John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, UK.
9
Department of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Sheffield, UK.
10
Translational Gastroenterology Unit, NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
11
Department of Medicine, University of Cambridge, Cambridge, UK.
12
Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Blizard Institute, Queen Mary University of London, London, UK.

Abstract

BACKGROUND:

Intestinal inflammation in Crohn's disease (CD) is caused by mucosal immune system reactivity to luminal antigen and results in debilitating symptoms, reduced quality of life, impaired work productivity and significant health care costs. Not all patients respond to conventional and biologic therapies, with chronic inflammation ensuing. Although surgical resection may be required, disease frequently returns and surgery may not be an option, or may be declined. Case reports suggest potential benefit after haematopoietic stem cell transplant (HSCT) for patients with refractory CD. The ASTIC trial asked whether HSCT could cure CD. Few patients achieved the primary endpoint of clinical remission for 3 months, off all medication with no evidence of active disease, and there were a high number of adverse events (AEs) and serious adverse events (SAEs), including one patient death. However, beneficial effects were observed in some aspects of disease activity. The ASTIClite trial will investigate these potential benefits and safety using a lower intensity regimen than ASTIC.

METHODS:

Ninety-nine participants will be recruited from secondary care IBD centres in the UK into a multicentre, randomised controlled trial (RCT, ASTIClite) and an observational follow-up, and randomised to autologous HSCT versus standard care (ratio 2:1). The primary endpoint is treatment success at week 48, defined as mucosal healing without surgery or death. Secondary endpoints relating to efficacy, safety and mechanistic analyses will be evaluated at week 8, 14, 24, 32, 40 and 48. Long-term safety of the low intensity HSCT regimen forms the primary endpoint for the EBMT follow-up study and will be assessed annually for 4-7 years.

DISCUSSION:

ASTIClite will compare HSCTlite with standard care with respect to safety, efficacy and quality of life, and capture outcomes allowing findings to be generalised to current clinical practice in the UK. It will also provide significant mechanistic insights into the immunological consequences of HSCTlite and its impact on treatment outcomes. The observational follow-up will provide information, which is currently unavailable for this population.

TRIAL REGISTRATION:

The ASTIClite RCT was registered on 31st October 2017 ( ISRCTN17160440 ) and the EBMT follow-up study on 19th January 2018 ( ISRCTN31981313 ).

KEYWORDS:

Autologous stem cell transplant; Crohn’s disease; Observational study; Randomised controlled trial

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