PreventiOn of DYSbioSis Complications With Autologous FMT in AML Patients

Phase 1

Completed

• Conditions: Leukemia, Myeloid, Acute
• Interventions: Drug: Autologous Fecal Microbiota Transplantation

• Registration Number: NCT02928523
• Lead Sponsor: MaaT Pharma

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-05-26
• Study Start: 2016-06
• Study First Submitted QC: 2016-10-06
• Study First Posted: 2016-10-10
• Primary Completion: 2017-08
• Study Completion: 2018-06-20
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-04
• Last Update Posted: 2020-09-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Autologous Fecal Microbiota Transplantation	Autologous Fecal Microbiota Transplantation	Patients will receive autologous fecal microbiota transplantation (MaaT011- 150 mL rectal enema) - 2 administrations 24 hours apart.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Definition of a dysbiosis biosignature using combination of biological parameters	40 days	Microbiota sequencing results will be correlated with immune parameters

Trial Locations

Locations (4)

HCL Lyon Sud; 🇫🇷 Pierre Benite, France

CHU Nantes; 🇫🇷 Nantes, France

Hopital Saint Antoine; 🇫🇷 Paris, France

IPC; 🇫🇷 Marseille, France