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ASTIClite: Autologous Stem cell Transplantation In refractory Crohn’s disease – Low Intensity Therapy Evaluation

The ASTIClite trial is testing whether autologous Haematopoietic Stem Cell Transplant (HSCT) is an effective treatment for Crohn’s disease in patients who have not responded to current licensed treatments.

More Information

Background

Crohn’s disease is a long term condition that causes inflammation of the lining of the digestive system. It most commonly occurs in the small and large intestine. There is no cure for Crohn’s disease. Current treatments include steroids, immunosuppressants, biologics (such as anti-TNF therapy or Vedolizumab) and specialised nutritional diets. These treatments are used to help reduce the degree of intestinal inflammation and hence the symptoms of Crohn’s disease; however some patients do not respond to these treatments or experience only temporary benefit, which is why the search for more effective treatments is continuing. An experimental treatment has been developed for severe Crohn’s disease, called ‘high dose immunoablation followed by autologous hematopoietic stem cell transplantation’. Hematopoietic blood stem cells are young, undifferentiated blood cells that can develop into differentiated ones, including lymphocytes. Over-active lymphocytes are thought to contribute to the development of Crohn’s disease. This treatment involves removing over-active lymphocytes from the blood and bone marrow and replacing them using blood stem cells taken from the patient earlier in the process.

At present, over 100 patients suffering from Crohn’s disease have been treated with stem cell transplantation worldwide. The results from those studies suggest that the therapy may be effective, but it cannot be concluded yet whether this treatment is better than any current standard treatment. In addition, participants in previous studies reported significant side effects from the high intensity treatment, most commonly relating to infections during the treatment. In response to this, a low intensity treatment has been developed, but not yet tested against the current standard treatment.

The ASTIClite Trial

The ASTIClite trial aims to assess whether stem cell transplantation, with a low intensity treatment regimen, can reduce the symptoms and activity of Crohn’s disease and enhance quality of life, compared to current standard care. The trial will also assess the safety of the procedure, explore the mechanisms involved in immune reconstitution and whether patients who do experience recurrent disease after the stem cell transplant will respond to treatments which had not worked previously. Finally, we will assess the long-term safety and efficacy in patients undergoing stem cell transplantation over a minimum of a further 4 years.

Potential participants will be discussed by a multidisciplinary team of gastroenterologists and haematologists to ensure stem cell transplantation would be appropriate. After informed consent, they will then undergo a series of screening investigations to confirm they meet the inclusion criteria for the trial. If eligible, they will be randomised to either receive the HSCT or usual care. Two patients will receive stem cell transplant for each patient that receives usual care.

Usual care can be any current treatment available for Crohn’s disease, except for stem cell transplant. For patients who are randomised to the transplant, stem cells will be removed (harvested) from patients in a process called mobilisation and stored for later use. Patients will then undergo chemotherapy to eliminate their immune cells. Then, the stem cells that were harvested earlier are transplanted (re-infused) into the patients’ blood. The re-infused stem cells give rise to a new generation of immune cells, replacing cells of the original ‘sick’ immune system.

Both groups will be followed intensively for 48 weeks. By comparing the progress of patients who undergo stem cell transplantation with those who receive usual care, the study will allow the value of stem cell transplantation to be assessed. Patients will also be invited to consent to a longer term follow up study, which will collect data on the safety and efficacy of the HSCT procedure for at least a further four years after the main trial. This data will be collected through the EBMT registry.

Participating Sites

If you have any questions, please contact us on our central team email address: asticlite@sheffield.ac.uk

Site

Principal Investigator

Lead Haematologist

Barts Health NHS Trust Prof James Lindsay Prof John Gribben
Cambridge University Hospitals NHS Foundation Trust Dr Miles Parkes

Dr Ben Uttenthal

Edinburgh Western General Hospital, NHS Lothian Dr Shahida Din Dr Peter Johnson
Guy’s & St Thomas’ NHS Foundation Trust
(Transplant Centre: King’s College Hospital NHS Foundation Trust)
Dr Peter Irving Dr Majid Kazmi
Royal Liverpool and Broadgreen University Hospital NHS Trust
(Transplant Centre: Clatterbridge Cancer Centre NHS Foundation Trust)
Dr Sreedhar Subramanian Dr Amit Patel
Nottingham University Hospitals NHS Trust Dr Gordon Moran

Dr Jenny Byrne

Oxford University Hospitals NHS Foundation Trust Prof Simon Travis Dr Andy Peniket
Sheffield Teaching Hospitals NHS Foundation Trust Prof Alan Lobo Prof John Snowden

Latest News

We are happy to announce that the following sites are now open to recruitment!

  • Barts Health (opened to recruitment on the 9th of May 2018)
  • Sheffield (opened to recruitment on the 11th of June 2018)
  • Nottingham (opened to recruitment on the 20th of August 2018)
  • Liverpool (opened to recruitment on the 28th of August 2018)
  • Cambridge (opened to recruitment on the 29th of August 2018)
  • Oxford (opened to recruitment on the 05th of October 2018)
  • Guys and St Thomas' (opened to recruitment on the 18th of February 2019, patients randomised to the intervention at this site will be treated at King's College Hospital)
  • Edinburgh (opened to recruitment on the 15th of March 2019)

We would like to thank the study teams at all our sites for their hard work at this time.

Name

Role Organisation Contact

Prof James Lindsay

Chief Investigator Bart’s Health NHS Trust

james.lindsay@bartshealth.nhs.net

Prof John Snowden Lead Haematologist Sheffield Teaching Hospitals NHS Foundation Trust john.snowden@sth.nhs.uk
Dr Daniel Hind Assistant Director, CTRU CTRU, University of Sheffield

d.hind@sheffield.ac.uk
+44 (0)114 222 0707

Diana Papaioannou Research Fellow CTRU, University of Sheffield

d.papaioannou@sheffield.ac.uk
+44 (0)114 222 0766

Lizzie Swaby Trial Manager CTRU, University of Sheffield

e.a.swaby@sheffield.ac.uk
+44 (0)114 222 4023

Katie Mellor

Research Assistant CTRU, University of Sheffield

k.j.mellor@sheffield.ac.uk
+44 (0)114 222 0760

Heather Dakin Trials Support Officer CTRU, University of Sheffield

h.dakin@sheffield.ac.uk
+44 (0)114 222 6385

Mike Bradburn Senior Medical Statistician CTRU, University of Sheffield

m.bradburn@sheffield.ac.uk
+44 (0)114 222 0706

Ellen Lee Statistician CTRU, University of Sheffield

e.lee@sheffield.ac.uk
+44 (0)114 222 0805

Laura Mandefield Statistician CTRU, University of Sheffield

l.mandefield@sheffield.ac.uk
+44 (0)114 222 0750

Amanda Loban,
Kirsty Pemberton
Chris Turtle
Emily Turton

Data Management Team CTRU, University of Sheffield

asticlite-dm-group@sheffield.ac.uk

Funder

This project is funded by the Efficacy and Mechanism Evaluation (EME) Programme, an MRC and NIHR partnership (project number 15/178/09). The views expressed in this publication are those of the author(s) and not necessarily those of the MRC, NHS, NIHR or the Department of Health.

Sponsor

Bart’s Health NHS Foundation Trust