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
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Changes in gut microbiota composition in patients with acute myeloid leukemia before, during and after induction therapy
研究概览
简要总结
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].
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Changes in gut microbiota composition in patients with acute myeloid leukemia before, during and after induction therapy
时间窗: 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
时间窗: 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
次要结局
- 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.)
- 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)
- 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)
- 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.)
- 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.)