Investigation of the Gut Microbiota in Acute Myeloid Leukemia Receiving Two Different Induction Therapies
- Conditions
- Acute Myeloid LeukemiaGut MicrobiotaInfectionsAdult
- Interventions
- Other: collection of biological samples and clinical data
- Registration Number
- NCT05123352
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 60
- Male or female, 65> =Age (years) >= 18;
- Newly diagnosed as AML patients according to World Health Organization (WHO) classification;
- Eastern Cooperative Oncology Group (ECOG) Performance status of 0,1,2;
- Patients will receive standard intensive chemotherapy (7+3) or bcl-2 inhibitor-based targeted therapy;
- Patients have not received prior therapy for AML (except hydroxycarbamide);
- 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);
- Renal function with creatinine clearance rate (Ccr) higher than 30 ml/min;
- 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.
- Acute promyeloid leukemia;
- AML with central nervous system (CNS) infiltration;
- Any history of chronic intestinal affections (Crohn disease, inflammatory bowel disease, gluten intolerance) or gastrointestinal surgery;
- HIV infection, Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment;
- Severe and active infection that is difficult to control and cannot tolerate induction therapy;
- Female who are pregnant, breast feeding or childbearing potential without a negative urine pregnancy test at screen;
- Antibiotic exposure within 30 days before enrollment (carbapenems and/or tigecycline were not included, penicillin, cephalosporins and quinolones could be included)
- Patients reject to participate in the study;
- Patients with severe heart failure (grade 3-4) or patients deemed unsuitable for enrolment by the investigator.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Standard intensive chemotherapy collection of biological samples and clinical data 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). Bcl-2 inhibitor-based targeted therapy collection of biological samples and clinical data 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.
- Primary Outcome Measures
Name Time Method Changes in gut microbiota composition in patients with acute myeloid leukemia before, during and after induction therapy 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
Changes in metabolites composition of blood in patients with acute myeloid leukemia before, during and after induction therapy 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
- Secondary Outcome Measures
Name Time Method Infection rate during 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. Infection rate of patients with acute myeloid leukemia after two different induction therapy
Changes in immune cells of blood in patients with acute myeloid leukemia before, during and after induction therapy 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
Changes of gut permeability markers and microbial compounds of blood in patients with acute myeloid leukemia before, during and after induction therapy Day 0 i.e.: blood sampling is done at time of diagnosis before induction therapy ELISA (in pg/ml)
Changes in number of participants with treatment related-related adverse events as assessed by CTCAE v4.0 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)
Rate of complete remission 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
Trial Locations
- Locations (1)
The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology
🇨🇳Suzhou, Jiangsu, China