The Gut Microbiome and Sorafenib Maintenance Therapy in FMS-like Tyrosine Kinase 3 (FLT3)/Internal Tandem Duplication (ITD) Positive Acute Myeloid Leukemia (AML) Patients After Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT)
Overview
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 37
- Locations
- 1
- Primary Endpoint
- Variation of Gut Microbiota Composition and Diversity
Overview
Brief Summary
This prospective trial investigates the effect of sorafenib maintenance therapy in FLT3-ITD positive AML patients after allo-HSCT in terms of gut microbiome.
Detailed Description
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. Some studies show that gut microbiome is associated with graft-versus-host-disease (GVHD) and GVL. However, the effect of gut microbiome on sorafenib maintenance after allo-HSCT remains unknown.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •FLT3-ITD Positive AML
- •Allo-HSCT Recipients
Exclusion Criteria
- •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)
Arms & Interventions
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).
Intervention: Sorafenib (Drug)
Outcomes
Primary Outcomes
Variation of Gut Microbiota Composition and Diversity
Time Frame: 3 months
Variation of gut microbiota composition and diversity, as determined by 16s rRNA sequencing of serial stool samples, during Sorafenib Maintenance Therapy.
Secondary Outcomes
- NRM(1 year)
- LFS(1 year)
- Variation of gut barrier integrity(3 months)
- AEs(1 year)
- Chronic GVHD(1 year)
- OS(1 year)
- Relapse(1 year)
- Acute GVHD(100 days)
Investigators
Xuanli
professor
Nanfang Hospital, Southern Medical University