The Gut Microbiome in FLT3-ITD+ AML Undergoing Allo-HSCT With Or Without Sorafenib Maintenance After Allo-HSCT

Study Overview
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Brief Summary
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This prospective trial investigates the effect of sorafenib maintenance therapy in FLT3-ITD AML patients after allo-HSCT in terms of gut microbiome.

Detailed Description
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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.

Official Title
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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

Conditions
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Acute Myeloid Leukemia With FLT3/ITD Mutation, Allogeneic Hematopoietic Stem Cell Transplantation

Intervention / Treatment
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* Drug: Sorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: FLT3-ITD Positive AML Allo-HSCT Recipients Exclusion Criteria: 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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| sorafenib group<br>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). | Drug: Sorafenib<br>* 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).<br>* Other names: BAY 545-9085;|
| non-sorafenib group<br>FLT3-ITD+ AML patients who do not receive sorafenib maintenance therapy after Allo-HSCT. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variation of Gut Microbiota Composition and Diversity | Variation of gut microbiota composition and diversity, as determined by 16s rRNA sequencing of serial stool samples, during Sorafenib Maintenance Therapy. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variation of gut barrier integrity | As determined by serum levels of zonulin, I-FABP, and citrulline or other potential candidates. | 3 months | 
| NRM | Non-relapse mortality (NRM) | 1 year | 
| Acute GVHD | Acute Graft-Versus-Host-Disease | 100 days | 
| Chronic GVHD | Chronic Graft-Versus-Host-Disease | 1 year | 
| AEs | Adverse Events | 1 year | 
| OS | Overall survival | 1 year | 
| LFS | Leukemia-free survival | 1 year | 
| Relapse | Cumulative incidence of relapse | 1year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hematopoietic Stem Cell Transplantation, Gut Microbiome, Sorafenib, Acute Myeloid Leukemia, FLT3-ITD