Acute Myeloid Leukemia With FLT3/ITD Mutation, Allogeneic Hematopoietic Stem Cell Transplantation
Conditions
Keywords
Hematopoietic Stem Cell Transplantation, Gut Microbiome, Sorafenib, Acute Myeloid Leukemia, FLT3-ITD
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.
Interventions
DRUGSorafenib
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).
Sponsors
Nanfang Hospital, Southern Medical University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Variation of gut barrier integrity | 3 months | As determined by serum levels of zonulin, I-FABP, and citrulline or other potential candidates. |
| OS | 1 year | Overall survival |
| LFS | 1 year | Leukemia-free survival |
| Relapse | 1year | Cumulative incidence of relapse |
| AEs | 1 year | Adverse Events |
Countries
China
Contacts
Primary ContactLi Xuan, MD
Outcome results
None listed