PreventiOn of DYSbioSis Complications With Autologous FMT in AML Patients

Study Overview
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Brief Summary
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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.

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

Conditions
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Leukemia, Myeloid, Acute

Intervention / Treatment
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* Drug: Autologous Fecal Microbiota Transplantation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autologous Fecal Microbiota Transplantation