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临床试验/NCT05601895
NCT05601895招募中不适用

The Gut Microbiome Changes in FMS-like Tyrosine Kinase 3 (FLT3) Negative Acute Leukemia (AL) Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT) With or Without Sorafenib Maintenance Post-transplantation

Nanfang Hospital, Southern Medical University1 个研究点 分布在 1 个国家目标入组 60 人开始时间: 2022年10月1日最近更新:
适应症
干预措施
相关药物

试验速览

阶段
不适用
状态
招募中
入组人数
60
试验地点
1
主要终点
Variation of Gut Microbiota Composition and Diversity

研究概览

简要总结

This prospective trial investigates the effect of sorafenib maintenance therapy in FLT3 negative acute leukemia patients after allo-HSCT in terms of gut microbiome.

详细描述

Acute leukemia is a heterogeneous group of clonal diseases. Leukemia relapse remains the main cause of treatment failure, including the patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Sorafenib, an inhibitor of multiple kinases including FLT3, has shown promising activity in FLT3-ITD-positive AML. The investigator's previous studies demonstrated that sorafenib maintenance post-transplantation could improve the outcomes of FLT3-ITD positive AML patients, which was associated with sorafenib enhancing the graft-versus-leukemia (GVL) effect. Recent studies have shown that sorafenib is also effective in patients with FLT3-negative acute leukemia. The investigator's previous exploratory study found that salvage therapy such as sorafenib combined with chemotherapy and donor lymphocyte infusion could significantly improve the CR rate and survival in patients with recurrent FLT3-negative acute leukemia after allo-HSC. More and more studies have shown that sorafenib and allo-HSCT have synergistic GVL effect. Some studies have demonstrated that gut microbiome is associated with graft-versus-host-disease (GVHD) and GVL. However, the exact mechanism of sorafenib enhancing the GVL effect and the influence of gut microbiome on sorafenib maintenance after allo-HSCT in FLT3 negative acute leukemia patients remain unknown.

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

入选标准

  • FLT3 Negative Acute Leukemia
  • Allo-HSCT Recipients

排除标准

  • intolerance to sorafenib pretransplantation
  • cardiac dysfunction (particularly congestive heart failure)
  • hepatic abnormalities (bilirubin ≥ 3 mg/dL, aminotransferase> 2 times the upper limit of normal)
  • renal dysfunction (creatinine clearance rate < 30 mL/min)
  • Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure)
  • Patients with any conditions not suitable for the trial (according to the investigators' decision)

研究组 & 干预措施

sorafenib group

FLT3- acute leukemia patients who receive sorafenib maintenance therapy after allo-HSCT. Sorafenib will be used from day 30 to 180 post-transplantation. The initial dose of sorafenib is 400 mg orally twice daily and is adjusted in case of suspected toxicity or resistance (dose range, 200-800 mg daily).

干预措施: Sorafenib (Drug)

结局指标

主要结局

Variation of Gut Microbiota Composition and Diversity

时间窗: 3 months

Variation of gut microbiota composition and diversity, as determined by 16sV3V4 rRNA sequencing of serial stool samples, during Sorafenib maintenance therapy and the period without Sorafenib maintenance.

次要结局

  • Chronic GVHD(1 year)
  • Relapse(1 year)
  • Variation of gut barrier integrity(3 months)
  • AEs(1 year)
  • NRM(1 year)
  • Acute GVHD(100 days)
  • OS(1 year)
  • LFS(1 year)

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

Qifa Liu

professor

Nanfang Hospital, Southern Medical University

研究点 (1)

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