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

Recruiting

• Conditions: Acute Myeloid Leukemia With FLT3/ITD Mutation; Allogeneic Hematopoietic Stem Cell Transplantation
• Interventions: Drug: Sorafenib

• Registration Number: NCT05596981
• Lead Sponsor: Nanfang Hospital, Southern Medical University

Brief Summary

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

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.

Study Timeline

• Status Verified: 2022-10
• Study Start: 2022-10-01
• Study First Submitted: 2022-10-25
• Study First Submitted QC: 2022-10-25
• Last Update Submitted: 2022-10-25
• Study First Posted: 2022-10-27
• Last Update Posted: 2022-10-27
• Primary Completion: 2023-12-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
sorafenib group	Sorafenib	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).

Primary Outcome Measures

Name	Time	Method
Variation of Gut Microbiota Composition and Diversity	3 months	Variation of gut microbiota composition and diversity, as determined by 16s rRNA sequencing of serial stool samples, during Sorafenib Maintenance Therapy.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Department of Hematology,Nanfang Hospital, Southern Medical University; 🇨🇳 Guangzhou, Guangdong, China