Gut microbiota restoration with oral pooled fecal microbiotherapy after intensive chemotherapy: the phase 1b CIMON trial

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.

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Publication Details

Journal
Blood Advances
Published
2025-04-08
DOI
https://doi.org/10.1182/bloodadvances.2024015571
Citations
3
Primary Topic
Neutropenia and Cancer Infections
Type
article
Field-Weighted Citation Impact
3.14
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article

Gut microbiota restoration with oral pooled fecal microbiotherapy after intensive chemotherapy: the phase 1b CIMON trial

Christian Récher, Sylvain Thépot, Michael L. Loschi, Mohamad Mohty et al.
3 citations
Blood Advances
Neutropenia and Cancer Infections
3.14
article

Gut microbiota restoration with oral pooled fecal microbiotherapy after intensive chemotherapy: the phase 1b CIMON trial

Christian Récher, Sylvain Thépot, Michael L. Loschi, Mohamad Mohty, Pierre Bories, Delphine Lebon, Juliette Jouve, Joël Doré, Cyrielle Gasc, Antoine Sabourin, Benoît Levast, Mathieu Meunier, Emmanuel Prestat, Thomas Cluzeau, Martin Carré, Émilie Plantamura, Béatrice Gaugler, O. Legrand, Marianne Schwarz, Florent Malard, Magalie Joris
article en
3 citations

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.

Blood AdvancesVol. 9(15)
Université Toulouse III - Paul Sabatier (FR), Inserm (FR), Université Paris-Saclay (FR), Centre Hospitalier Universitaire de Grenoble (FR), Centre Hospitalier Universitaire de Nice (FR), Centre Hospitalier Universitaire de Toulouse (FR), Sorbonne Université (FR), Institut de Chimie de Nice (FR), Centre de Recherches en Cancérologie de Toulouse (FR), Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR), Centre Hospitalier Universitaire Amiens-Picardie (FR), Assistance Publique – Hôpitaux de Paris (FR), Institut universitaire du cancer de Toulouse Oncopole (FR), Hôpital Saint-Antoine (FR), Centre Hospitalier Universitaire d'Angers (FR), Erytech Pharma (France) (FR), Centre de Recherche Saint-Antoine (FR), Agir Pour les Maladies Chroniques (FR), Université d'Angers (FR), Université Grenoble Alpes (FR)
Openalex Percentile: Top 8%
Neutropenia and Cancer Infections
3.14
DOIOpen Access PDFOpenAlex
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