Clinical trial NCT05601895: The Gut Microbiome in FLT3- AL Undergoing Allo-HSCT With Or Without Sorafenib Maintenance
Official title: The Gut Microbiome Changes in FMS-like Tyrosine Kinase 3 (FLT3) Negative Acute Leukemia (AL) Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT) With or Without Sorafenib Maintenance Post-transplantation
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Acute Leukemia
Allogeneic Hematopoietic Stem Cell Transplantation
Keywords: Hematopoietic Stem Cell Transplantation
Gut Microbiome
Sorafenib
Acute Leukemia
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
First posted: 2022-11-01
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: FLT3 Negative Acute Leukemia Undergoing Allo-HSCT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Variation of Gut Microbiota Composition and Diversity
timeFrame: 3 months
Secondary outcomes:
measure: Variation of gut barrier integrity
timeFrame: 3 months
measure: NRM
timeFrame: 1 year
measure: Acute GVHD
timeFrame: 100 days
measure: Chronic GVHD
timeFrame: 1 year
measure: AEs
timeFrame: 1 year
measure: OS
timeFrame: 1 year
measure: LFS
timeFrame: 1 year
measure: Relapse
timeFrame: 1 year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Department of Hematology,Nanfang Hospital, Southern Medical University
state: Guangdong
Study officials:
affiliation: Nanfang Hospital, Southern Medical University
name: Li Xuan, MD
role: PRINCIPAL_INVESTIGATOR
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