Clinical trial NCT05123352: Investigation of the Gut Microbiota in Acute Myeloid Leukemia Receiving Two Different Induction Therapies
Official title: Investigation of the Gut Microbiota Evaluated by Metagenomic Next-Generation Sequencing (mNGS) in Acute Myeloid Leukemia Receiving Standard Intensive Chemotherapy or Bcl-2 Inhibitor-based Targeted Induction Therapy
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Acute Myeloid Leukemia
Adult
Gut Microbiota
Infections
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
First posted: 2021-11-17
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Candidates will come from patients with newly diagnosed acute myeloid leukemia (AML) in the First Affiliated Hospital of Soochow University from November 2021. Participants should meet the inclusion criteria and not meet exclusion criteria.

Brief summary: In this observational single-center cohort study, metagenomic Next-Generation Sequencing (mNGS) will be used to investigate the features and changes of gut microbiota in acute myeloid leukemia (AML) patients during the treatment of two different induction therapy regimens \[standard intensive chemotherapy (7+3) or bcl-2 inhibitor-based targeted therapy\].

Detailed description: Infections remain one of the major complications during induction therapy of acute myelocytic leukemia (AML). Previous studies have shown that the variation of gut microbiota was an effective predictor for infection development of AML during induction therapy. A growing number of patients with AML received bcl-2 inhibitor-based targeted induction therapy. The investigators assume that there are different effects of bcl-2 inhibitor-based induction therapy on gut microbiota compared with standard intensive chemotherapy (7+3 regimen). Metagenomic Next-Generation Sequencing (mNGS) will be used to perform the investigation of gut microbiota in AML receiving two different induction therapies. And the relationships of gut microbiota with infection complication will be analyzed.

Eligibility criteria: Inclusion Criteria:

1. Male or female, 65\> =Age (years) \>= 18;
2. Newly diagnosed as AML patients according to World Health Organization (WHO) classification;
3. Eastern Cooperative Oncology Group (ECOG) Performance status of 0,1,2;
4. Patients will receive standard intensive chemotherapy (7+3) or bcl-2 inhibitor-based targeted therapy;
5. Patients have not received prior therapy for AML (except hydroxycarbamide);
6. Liver function: Total bilirubin lower than 3 upper limit of normal (ULN); Aspartate aminotransferase (AST) lower than 3 ULN; Alanine aminotransferase (ALT) lower than 3 ULN (except extramedullary infiltration of leukemia);
7. Renal function with creatinine clearance rate (Ccr) higher than 30 ml/min;
8. Patients who sign the informed consent must have the ability to understand and be willing to participate in the study and sign the informed consent.

Exclusion Criteria:

1. Acute promyeloid leukemia;
2. AML with central nervous system (CNS) infiltration;
3. Any history of chronic intestinal affections (Crohn disease, inflammatory bowel disease, gluten intolerance) or gastrointestinal surgery;
4. HIV infection, Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment;
5. Severe and active infection that is difficult to control and cannot tolerate induction therapy;
6. Female who are pregnant, breast feeding or childbearing potential without a negative urine pregnancy test at screen;
7. Antibiotic exposure within 30 days before enrollment (carbapenems and/or tigecycline were not included, penicillin, cephalosporins and quinolones could be included)
8. Patients reject to participate in the study;
9. Patients with severe heart failure (grade 3-4) or patients deemed unsuitable for enrolment by the investigator.

Primary outcomes:
measure: Changes in gut microbiota composition in patients with acute myeloid leukemia before, during and after induction therapy
timeFrame: Day 0 i.e.: feces sampling is done at time of diagnosis before induction therapy
measure: Changes in metabolites composition of blood in patients with acute myeloid leukemia before, during and after induction therapy
timeFrame: Day 0 i.e.: blood sampling is done at time of diagnosis before induction therapy
Secondary outcomes:
measure: Changes in immune cells of blood in patients with acute myeloid leukemia before, during and after induction therapy
timeFrame: Day 0 i.e.: blood sampling is done at time of diagnosis before induction therapy
measure: Changes of gut permeability markers and microbial compounds of blood in patients with acute myeloid leukemia before, during and after induction therapy
timeFrame: Day 0 i.e.: blood sampling is done at time of diagnosis before induction therapy
measure: Infection rate during induction therapy
timeFrame: From date of first one cycle induction therapy start to the end of Cycle 1 (each cycle is 28 days) or death from any cause during Cycle 1 induction therapy.
measure: Rate of complete remission
timeFrame: From date of first one cycle induction therapy start to the end of Cycle 1 (each cycle is 28 days) or death from any cause during Cycle 1 induction therapy.
measure: Changes in number of participants with treatment related-related adverse events as assessed by CTCAE v4.0
timeFrame: From date of first one cycle induction therapy start to the end of Cycle 1 (each cycle is 28 days) or death from any cause during Cycle 1 induction therapy.
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology
name: Suning Chen, professor
role: PRINCIPAL_INVESTIGATOR
References: