Intestinal Microbiota Transplant Prior to Allogeneic Stem Cell Transplant (MAST) trial: study protocol for a multicentre, double-blinded, placebo-controlled, phase IIa trial
Julian R Marchesi,
Emma Nicholson,
Benjamin H Mullish,
Renuka Palanicawandar,
Graham Wheeler,
Francesca Kinsella,
Andrew J Innes,
Lauren A Roberts,
Shian Anim-Burton,
Lee Webber,
Nicholas A Johnson,
Rohma Ghani,
Pakhshan Farshi,
Anjum B Khan,
Panagiotis Kottaridis,
Pramila Krishnamurthy,
Frances Davies,
Jiří Pavlů
Affiliations
Julian R Marchesi
Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
Emma Nicholson
Department of Haematology, The Royal Marsden Hospital, London, UK
Benjamin H Mullish
Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
Renuka Palanicawandar
Centre for Haematology, Department of immunology and inflammation, Faculty of Medicine, Imperial College London, London, UK
Graham Wheeler
Imperial Clinical Trials Unit, School of Public Health, Faculty of Medicine, Imperial College London, London, UK
Francesca Kinsella
Department of Haematology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
Andrew J Innes
Centre for Haematology, Department of immunology and inflammation, Faculty of Medicine, Imperial College London, London, UK
Lauren A Roberts
Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
Shian Anim-Burton
Cancer Research UK Imperial Centre, Clinical Trials Section, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK
Lee Webber
Cancer Research UK Imperial Centre, Clinical Trials Section, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK
Nicholas A Johnson
Imperial Clinical Trials Unit, School of Public Health, Faculty of Medicine, Imperial College London, London, UK
Rohma Ghani
Division of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
Pakhshan Farshi
Department of Haematology, Manchester Royal Infirmary, Manchester, UK
Anjum B Khan
Department of Haematology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
Panagiotis Kottaridis
Department of Haematology, University College London Hospitals NHS Foundation Trust, London, UK
Pramila Krishnamurthy
Department of Haematology, King`s College Hospital NHS Foundation Trust, London, UK
Frances Davies
Department of Infectious Diseases, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK
Jiří Pavlů
Centre for Haematology, Department of immunology and inflammation, Faculty of Medicine, Imperial College London, London, UK
Introduction Lower diversity of the gut microbiome prior to allogeneic haematopoietic cell transplantation (HCT) correlates with reduced survival after the intervention. Most patients undergoing HCT for a haematological malignancy have previously received intensive chemotherapy, resulting in prolonged neutropenic episodes requiring broad-spectrum antibiotics; use of these has been linked to reduced microbiome diversity. Intestinal microbiota transplant (IMT) is a novel treatment approach that restores this diversity. We hypothesised that IMT performed prior to initiation of HCT conditioning restores microbiome diversity during the early stages of HCT, leading to decreased frequency of complications and improved outcomes of HCT.Methods and analysis 50 adult patients receiving allogeneic HCT will be recruited into this phase IIa trial and randomised 1:1 to receive capsulised IMT or matched placebo shortly prior to initiation of HCT conditioning and followed for up to 12 months. The primary outcome will be to assess the increase in alpha diversity between pre-IMT and that measured at ~42 days after IMT administration (day +28 of HCT), comparing the difference between patients receiving IMT compared with placebo. Secondary outcomes will include tolerability, the dynamics of gut microbiome diversity metrics and taxonomy over all time points assessed, as well as clinical outcomes (including burden of invasive infections, days of fever, admission to intensive care, development of graft-vs-host disease and mortality).Ethics and dissemination This study was approved by a UK Research Ethics Committee (REC reference: 23/NE/0105). Dissemination of results will be in concert with patient and public involvement group input and is expected to be primarily via abstract presentation at conferences and manuscripts in peer-reviewed journals.Trial registration numbers NCT6355583; EudraCT: 2022-003617-10.
