Gut microbiota restoration with oral pooled fecal microbiotherapy after intensive chemotherapy: the phase 1b CIMON trial
Year: 2025
Type: article
Study design: Clinical Trial
Abstract: ABSTRACT: Intensive induction chemotherapy (IC) combined with broad-spectrum antibiotics for acute myeloid leukemia (AML) leads to gut microbiota dysbiosis, promoting pathological conditions and an increased incidence of complications, possibly limiting eligibility to allogeneic hematopoietic cell transplantation (alloHCT). The purpose of this dose-ranging phase 1 study (CIMON) was to evaluate the first-in-man use of MaaT033, a pooled, allogeneic, lyophilized, and standardized fecal microbiotherapeutic product, formulated as a delayed-release capsule for oral administration. Primary objectives of the study were to evaluate the maximum tolerable dose of MaaT033 in 21 patients with AML having undergone IC and antibiotics. Secondary objectives were to assess MaaT033 safety, its efficacy in restoring the patients' gut microbiome using shotgun sequencing to evaluate the recommended dose regimen, and patient compliance. MaaT033 was shown to be safe and effective for gut microbiota restoration in patients with AML receiving IC and antibiotics, with an excellent gut microbiota reconstruction based on diversity indices at the species level and restoration of microbial communities close to the composition of the drug product. The maximum tolerable dose of MaaT033 was not determined because the interim results suggested adequate efficacy as measured by engraftment at lower doses (3 capsules per day). Moreover, inflammatory markers (C-reactive protein, interleukin-6) decrease with treatment, whereas short-chain fatty acids increase over time. A randomized, placebo-controlled phase 2b trial, in recipients of alloHCT patients is ongoing. This trial was registered at www.clinicaltrials.gov as #NCT04150393.
Source: Blood Advances
Authors: Florent Malard, Sylvain Thepot, Thomas Cluzeau, Martin Carré, Delphine Lebon, Pierre Bories, Ollivier Legrand, Marianne Schwarz, Michael Loschi, Mathieu Meunier, Magalie Joris, Cyrielle Gasc, Juliette Jouve, Benoît Levast, Emilie Plantamura, Emmanuel Prestat, Antoine Sabourin, Béatrice Gaugler, Joel Dore, Christian Récher, Mohamad Mohty
Institutions: Inserm, Assistance Publique – Hôpitaux de Paris, Hôpital Saint-Antoine, Centre de Recherche Saint-Antoine, Centre Hospitalier Universitaire d'Angers, Université d'Angers, Université Côte d'Azur, Centre Hospitalier Universitaire de Nice, Centre Hospitalier Universitaire de Grenoble, Université Grenoble Alpes, Centre Hospitalier Universitaire Amiens-Picardie, Université Toulouse III - Paul Sabatier, Centre Hospitalier Universitaire de Toulouse, Centre de Recherches en Cancérologie de Toulouse, Institut universitaire du cancer de Toulouse Oncopole, Université de Toulouse, MaaT Pharma (France), Université Paris-Saclay, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, MetaGenoPolis, Sorbonne Université
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,800
OpenAlex ID: W4409263791