Investigation of the Gut Microbiota in Acute Myeloid Leukemia Receiving Two Different Induction Therapies

November 5, 2021 updated by: The First Affiliated Hospital of Soochow University

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

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].

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Anticipated)

60

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Jiangsu
      • Suzhou, Jiangsu, China, 215000
        • The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Standard intensive chemotherapy
Patients with acute myeloid leukemia in this cohort will receive standard induction chemotherapy that combines seven days of cytarabine and three days of anthracycline (7+3 regimen).
Other: collection of biological samples and clinical data
blood and feces samples
Bcl-2 inhibitor-based targeted therapy
Patients with acute myeloid leukemia in this cohort will receive Bcl-2 inhibitor-based targeted therapy, such as combination of bcl-2 inhibitor plus decitabine/azacitidine with or without sorafenib.
Other: collection of biological samples and clinical data
blood and feces samples

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in gut microbiota composition in patients with acute myeloid leukemia before, during and after induction therapy
Time Frame: Day 0 i.e.: feces sampling is done at time of diagnosis before induction therapy
Sequencing DNA extracts from patients' feces to obtain the description of gut microbiota composition in those patients
Day 0 i.e.: feces sampling is done at time of diagnosis before induction therapy
Changes in metabolites composition of blood in patients with acute myeloid leukemia before, during and after induction therapy
Time Frame: Day 0 i.e.: blood sampling is done at time of diagnosis before induction therapy
Metabolomics performed on patients' blood to report the metabolites composition in those patients
Day 0 i.e.: blood sampling is done at time of diagnosis before induction therapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in immune cells of blood in patients with acute myeloid leukemia before, during and after induction therapy
Time Frame: Day 0 i.e.: blood sampling is done at time of diagnosis before induction therapy
Immunomicin performed on patients' blood to report the composition of immune cells in those patients
Day 0 i.e.: blood sampling is done at time of diagnosis before induction therapy
Changes of gut permeability markers and microbial compounds of blood in patients with acute myeloid leukemia before, during and after induction therapy
Time Frame: Day 0 i.e.: blood sampling is done at time of diagnosis before induction therapy
ELISA (in pg/ml)
Day 0 i.e.: blood sampling is done at time of diagnosis before induction therapy
Infection rate during induction therapy
Time Frame: 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.
Infection rate of patients with acute myeloid leukemia after two different induction therapy
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.
Rate of complete remission
Time Frame: 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.
Complete remission after one cycle of induction therapy
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.
Changes in number of participants with treatment related-related adverse events as assessed by CTCAE v4.0
Time Frame: 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.
CTCAE (common terminology criteria for adverse event version 4)
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The First Affiliated Hospital of Soochow University

Investigators

  • Principal Investigator: Suning Chen, Professor, The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

November 1, 2021

Primary Completion (Anticipated)

June 1, 2022

Study Completion (Anticipated)

November 1, 2022

Study Registration Dates

First Submitted

October 26, 2021

First Submitted That Met QC Criteria

November 5, 2021

First Posted (Actual)

November 17, 2021

Study Record Updates

Last Update Posted (Actual)

November 17, 2021

Last Update Submitted That Met QC Criteria

November 5, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AML-GutMicrobiota01

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Infections

Clinical Trials on collection of biological samples and clinical data

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Austria

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe