Clinical trial NCT02928523: PreventiOn of DYSbioSis Complications With Autologous FMT in AML Patients
Official title: PreventiOn of DYSbioSis Complications With Autologous Fecal Microbiota Transplantation in acutE myEloid Leukemia Patients Undergoing Intensive Treatment: A Feasibility and Safety Study ODYSSEE STUDY
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Leukemia, Myeloid, Acute
Keywords: Autologous Fecal Microbiota Transplantation
Lead sponsor: MaaT Pharma
Sponsor class: INDUSTRY
First posted: 2016-10-10
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Evaluation of AFMT efficacy in dysbiosis correction by measure of microbiota diversity
timeFrame: 40 days
measure: Evaluation of AFMT efficacy in MDRB eradication based on bacterial culture
timeFrame: 40 days
Secondary outcomes:
measure: Definition of a dysbiosis biosignature using combination of biological parameters
timeFrame: 40 days
Other outcomes:
Locations:
city: Marseille
country: France
facility: IPC
city: Nantes
country: France
facility: CHU Nantes
city: Paris
country: France
facility: Hopital Saint Antoine
city: Pierre Benite
country: France
facility: HCL Lyon Sud
Study officials:
affiliation: APHP
name: Mohamad Mohty, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.