PreventiOn of DYSbioSis Complications With Autologous FMT in AML Patients (ODYSSEE)

PreventiOn of DYSbioSis Complications With Autologous Fecal Microbiota Transplantation in acutE myEloid Leukemia Patients Undergoing Intensive Treatment: A Feasibility and Safety Study ODYSSEE STUDY

The investigators propose to use autologous fecal microbiota transplantation (AFMT) to acute myeloid leukemia (AML) patients treated with intensive chemotherapy and antibiotics in order to restore the balance of their intestinal microbiome and thereby eradicate treatment-induced multidrug resistant bacteria (MDRB), infection-related complications, as well as sequelae to the gastrointestinal tract. Therefore, the investigators propose to perform a single-arm multicentre prospective fecal microbiota transplantation (FMT) trial in AML patients receiving intensive chemotherapy, and who are usually heavily treated with broad-spectrum antibiotics during aplasia that generate a profound status of dysbiosis. For this purpose, at the time of admission and AML diagnosis, patients will be requested to donate stools that will be comprehensively screened, and if deemed appropriate according to protocol criteria, conditioned and stored frozen until future processing and transplantation after aplasia completion.

Study Overview

• Status: Completed
• Conditions: Leukemia, Myeloid, Acute
• Intervention / Treatment: Drug: Autologous Fecal Microbiota Transplantation

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Marseille, France, 13009
    • IPC
  • Nantes, France, 44000
    • CHU Nantes
  • Paris, France, 75012
    • Hopital Saint Antoine
  • Pierre Benite, France, 69310
    • HCL Lyon Sud

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients ≥ 18 and ≤ 75 years old with de novo diagnosis of AML or high-risk myelodysplastic syndrom for whom intensive induction chemotherapy is anticipated within 10 days after admission
• Patients willing to donate stool samples and to follow protocol recommendations
• Signature of informed and written consent

Exclusion Criteria:

• Acute promyelocytic leukemia (AML-M3)
• Known allergy or intolerance to trehalose or maltodextrin
• Pregnancy: positive urinary or blood test in female of childbearing potential
• Severe disease with a life expectancy < 3 months
• Other ongoing interventional protocol that might interfere with the study

• Non eligibility for collection of autologous stools upon admission:

  • Patients refusing to consent
  • Antibiotherapy at the time of study inclusion ≥ 4 days
  • Concomitant or previous diagnosis of a significant inflammatory bowel disease (UC, CD) or other progressive digestive disease requesting treatment or further medical exploration
  • Presence of severe colitis of any etiology at the time of admission or severe digestive disorders (acute or chronic diarrhea) within 3 months preceding inclusion
  • Patient getting a recent colonoscopy (within 3 months preceding inclusion)
• Detection of MDRB, pathogenic bacteria, parasites, norovirus and/or rotavirus during screening of autologous stool collected at baseline
• Non eligibility for inoculum transplantation: persistent mucositis, colitis, or haemorrhoids, presence of blood in more than 50% of patient's faeces the week preceding the transplantation
• Non feasibility of inoculum procedure: patient refusal; technical or biological mismatch of the inoculum
• Absence of effective contraceptive method for female of childbearing potential
• Lactation
• Inability to give an informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Autologous Fecal Microbiota Transplantation; Patients will receive autologous fecal microbiota transplantation (MaaT011- 150 mL rectal enema) - 2 administrations 24 hours apart.	Drug: Autologous Fecal Microbiota Transplantation; Other Names: MaaT011

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of AFMT efficacy in dysbiosis correction by measure of microbiota diversity	Comparison of Alpha and Beta diversity indexes at baseline, after chemotherapy and after AFMT will be performed	40 days
Evaluation of AFMT efficacy in MDRB eradication based on bacterial culture	MDRB carriage and resistome will be compared at baseline, after chemotherapy and after AFMT	40 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Definition of a dysbiosis biosignature using combination of biological parameters	Microbiota sequencing results will be correlated with immune parameters	40 days

Collaborators and Investigators

• Sponsor: MaaT Pharma
• Investigators: Study Chair: Mohamad Mohty, MD, PhD, APHP

Publications and helpful links

General Publications

• Malard F, Vekhoff A, Lapusan S, Isnard F, D'incan-Corda E, Rey J, Saillard C, Thomas X, Ducastelle-Lepretre S, Paubelle E, Larcher MV, Rocher C, Recher C, Tavitian S, Bertoli S, Michallet AS, Gilis L, Peterlin P, Chevallier P, Nguyen S, Plantamura E, Boucinha L, Gasc C, Michallet M, Dore J, Legrand O, Mohty M. Gut microbiota diversity after autologous fecal microbiota transfer in acute myeloid leukemia patients. Nat Commun. 2021 May 25;12(1):3084. doi: 10.1038/s41467-021-23376-6.

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Actual): August 1, 2017
• Study Completion (Actual): June 20, 2018

Study Registration Dates

• First Submitted: May 26, 2016
• First Submitted That Met QC Criteria: October 6, 2016
• First Posted (Estimate): October 10, 2016

Study Record Updates

• Last Update Posted (Actual): September 9, 2020
• Last Update Submitted That Met QC Criteria: September 4, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Autologous Fecal Microbiota Transplantation
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Dysbiosis
• Other Study ID Numbers: MPOH02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO