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

Abstract

Intensive 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 allogenic hematopoietic cell transplantation (alloHCT). The purpose of this dose-ranging phase I 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 AML patients having undergone IC and antibiotics. Secondary objectives were to assess MaaT033 safety, its efficacy in restoring the patients' gut microbiome using shotgun sequencing in order to evaluate the recommended dose regimen, and patient compliance (ClinicalTrials.gov number: NCT04150393). MaaT033 was shown to be safe and effective for gut microbiota restoration in AML patients 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. Moreover, inflammatory markers (C-reactive protein, interleukin-6) decrease with treatment, while short-chain fatty acids increase over time. A randomized, placebo-controlled phase IIb trial, in recipients of alloHCT patients in ongoing.