The Gut Microbiome in FLT3- AL Undergoing Allo-HSCT With Or Without Sorafenib Maintenance

Recruiting

• Conditions: Acute Leukemia; Allogeneic Hematopoietic Stem Cell Transplantation
• Interventions: Drug: Sorafenib

• Registration Number: NCT05601895
• Lead Sponsor: Nanfang Hospital, Southern Medical University

Brief Summary

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

Detailed Description

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.

Study Timeline

• Status Verified: 2022-10
• Study Start: 2022-10-01
• Study First Submitted: 2022-10-25
• Study First Submitted QC: 2022-10-28
• Last Update Submitted: 2022-10-28
• Study First Posted: 2022-11-01
• Last Update Posted: 2022-11-01
• Primary Completion: 2023-12-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

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

Inclusion Criteria

• FLT3 Negative Acute Leukemia
• 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)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
sorafenib group	Sorafenib	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).

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 16sV3V4 rRNA sequencing of serial stool samples, during Sorafenib maintenance therapy and the period without Sorafenib maintenance.

Secondary Outcome Measures

Name	Time	Method
NRM	1 year	Non-relapse mortality
OS	1 year	Overall Survival
Chronic GVHD	1 year	The cumulative incidence of overall grades of chronic GVHD will be assessed through 1 year after transplantation according to the 2014 NIH Consensus.
Relapse	1 year	Cumulative incidence of relapse
Variation of gut barrier integrity	3 months	As determined by serum levels of zonulin, I-FABP, and citrulline or other potential candidates.
AEs	1 year	Adverse Events
Acute GVHD	100 days	The cumulative incidence of overall grades II-IV and grades III-IV acute GVHD will be assessed through six months after transplantation. Acute GVHD will be assessed using the Mount Sinai Acute GVHD International Consortium (MAGIC) criteria.
LFS	1 year	Leukemia-Free Survival

Trial Locations

Locations (1)

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