ASTIClite

• Research type

  Research Study

• Full title

  Autologous Stem cell Transplantation In refractory Crohn's disease - Low Intensity Therapy Evaluation

• IRAS ID

  220495

• Contact name

  James Lindsay

• Contact email

  James.Lindsay@bartshealth.nhs.uk

• Sponsor organisation

  Barts Health NHS Trust

• Eudract number

  2017-002545-30

• ISRCTN Number

  ISRCTN17160440

• Duration of Study in the UK

  4 years, 7 months, 31 days

• Research summary

  Research Summary

  Crohn’s disease is a long term condition that causes inflammation of the lining of the digestive system. There is no cure for Crohn's disease and current treatments only reduce symptoms and often carry complicated side effects. In addition, some patients fail to respond to these treatments or experience only temporary benefit. In the absence of an effective alternative, patients are likely to be exposed to a sequence of expensive therapies with diminishing potential for benefit and increasing risk of harm.

  An alternative therapy is haematopoietic stem cell transplantation (HSCT). This trial aims to evaluate whether HSCT with a low intensity treatment regime, can reduce the symptoms and activity of Crohn’s disease and enhance quality of life.

  Patients with Crohn’s disease that is resistant to current therapies will be recruited from across the UK. Patients will be randomly assigned to receive HSCT or the usual care offered by their local NHS organisation. For patients who receive the HSCT therapy, some stem cells will be removed (harvested) from the patient and stored for later use. The patient will then undergo a process to eliminate their immune cells. Then the stem cells that were harvested earlier are transplanted (re-infused) back into the patient's blood. The re-infused stem cells give rise to a new generation of immune cells, replacing cells of the original ‘sick’ immune system.

  The trial will allow the value of stem cell transplantation to be assessed by comparing the progress of patients who undergo stem cell transplantation with those who receive usual care. Imaging techniques and patient reported symptom measures will be used to measure symptom progression. The study will also explore the mechanisms involved in rebuilding the immune system and reactivity to biologic therapies after HSCT by comparing tissue samples collected over course of the trial.

  Summary of Results

  Background Crohn’s disease occurs when the gut immune system reacts to its bacterial content, causing bowel inflammation. For some patients, standard treatments for Crohn’s disease are ineffective, leading to debilitating symptoms, poor quality of life, and the possibility of operations which can result in a stoma. Initial reports suggested that treatment resistant Crohn’s disease could be improved with stem cell transplantation (HSCT), where a patient’s own immune stem cells are returned to them after their current immune system is wiped out by chemotherapy.

  Objectives
  ASTIClite aimed to test HSCT with low dose chemotherapy, to investigate whether this could be a safe and effective treatment. ASTIClite also looked at how HSCT works.

  Methods
  ASTIClite was a randomised controlled trial, which aimed to recruit 99 patients with treatment resistant Crohn’s disease, across 8 UK NHS centres. Patients were followed up every few weeks, and at 48 weeks, we assessed whether HSCT was more likely to lead to healing of intestinal inflammation than standard care. Some patients experienced severe side effects, and the trial was closed early after 23 patients were recruited.

  Results
  23 patients joined ASTIClite (13 HSCT, 10 usual care). 13 patients in total had assessable colonoscopies at 48 weeks. 3/7 HSCT patients had absence of ulceration, with 0/6 in the usual care group. 3/6 HSCT patients had disease remission, and 0/3 usual care. All patients in the HSCT group experienced at least one side effect (38 serious side effects in total), including two patients who died. In the usual care group 4/10 patients experienced adverse events (16 serious adverse events in total).

  Conclusions
  Although HSCT using the ASTIClite regimen reduced Crohn’s disease activity in some patients, the numbers of serious and unexpected side effects mean that this treatment plan would be unsuitable for future clinical use.

• REC name

  London - Chelsea Research Ethics Committee

• REC reference

  17/LO/1690

• Date of REC Opinion

  6 Nov 2017

• REC opinion

  Further Information Favourable Opinion