A study protocol for a double-blinded, randomised, placebo-controlled trial on the use of encapsulated FMT for reducing the side effects of HSCT: the HSCT-BIOME study

Anna Li, Sam P. Costello, Robert V. Bryant, Sarah Haylock-Jacobs, Craig Haifer, Cindy Lee, David Yeung, Pratyush Giri, Danielle Blunt, Joanne B. Bowen, Feargal J. Ryan, Angelina Yong, Hannah R. Wardill

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Abstract

BACKGROUND: The composition of the gut microbiota both prior to and after haematopoietic stem cell transplantation (HSCT) is increasingly implicated in the outcomes of HSCT, including infections, poor immune reconstitution and disease relapse. Faecal microbiota transplantation (FMT) offers a potential strategy of supporting the gut microbiota and improve HSCT outcomes. Although FMT has been investigated in HSCT recipients, it has largely been evaluated therapeutically for indications such as infection, or once immunocompetency is regained. METHODS: Peri-HSCT FMT (i.e. before and after HSCT) will be administered to eligible participants (adults undergoing autologous HSCT for a haematological malignancy) over two courses, with the first delivered immediately prior to conditioning and the second starting when ANC > 0.8. Following an open-label, safety run in (N = 5), peri-HSCT FMT will be evaluated for its efficacy in 51 participants, randomised 2:1 to FMT or placebo. The primary outcome is the proportion of participants who develop severe gastrointestinal toxicity defined by 3 consecutive days of severe diarrhoea (Bristol Stool Chart 6+), at a frequency of 4 + bowel movements/day within 3 weeks of HSCT. Safety is defined as the incidence of treatment-emergent adverse events (TE-AEs). Tolerability is defined as the incidence of TE-AEs and adherence to FMT. DISCUSSION: The HSCT-BIOME study is a multi-centre, double-blind, randomised placebo-controlled trial designed to determine the tolerability, safety and efficacy of orally-administered encapsulated FMT to promote the stability of the gastrointestinal microenvironment for HSCT recipients. Peri-HSCT delivered FMT is hypothesised to promote microbial composition both before and following HSCT. Thus, the study will determine if administration of FMT post-HSCT during the neutropenic phase will enhance efficacy. 

Original languageEnglish
Article number656
Number of pages8
JournalBMC Cancer
Volume25
Issue number1
DOIs
Publication statusPublished - Dec 2025

Keywords

  • Autologous haematopoeitic stem cell transplantation
  • Capsule fecal microbiota transplantation
  • Peri-HSCT fecal microbiota transplantation

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