The Gut Microbiome Changes in FMS-like Tyrosine Kinase 3 (FLT3)-ITD Positive Acute Myeloid Leukemia Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation With or Without Sorafenib Maintenance Post-transplantation
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-ITD AML patients after allo-HSCT in terms of gut microbiome.
详细描述
Hematopoietic stem cell transplantation (HSCT) is used as a potentially curative therapy for patients with hematopoietic malignancies. Sorafenib, an inhibitor of multiple kinases including FLT3, has shown promising activity in FLT3-ITD-positive AML. Our previous studies demonstrated that sorafenib maintenance post-transplantation could improve the outcomes of FLT3-ITD-positive AML patients, which is associated with sorafenib enhancing the graft-versus-leukemia (GVL) effect. Recent studies show 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 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
- 否
入选标准
- •FLT3-ITD Positive AML
- •Allo-HSCT Recipients
排除标准
- •Intolerance to sorafenib pre-transplantation
- •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-ITD+ AML 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 16s rRNA sequencing of serial stool samples, during Sorafenib Maintenance Therapy.
次要结局
- Chronic GVHD(1 year)
- OS(1 year)
- NRM(1 year)
- Acute GVHD(100 days)
- AEs(1 year)
- Variation of gut barrier integrity(3 months)
- LFS(1 year)
- Relapse(1year)
研究者
Xuanli
professor
Nanfang Hospital, Southern Medical University