Sorafenib for Prophylaxis of Leukemia Relapse in Allo-HSCT Recipients With FLT3-ITD Positive AML

Conditions

Acute Myeloid Leukemia, Hematopoietic Stem Cell Transplantation

Keywords

Acute Myeloid Leukemia, FLT3-ITD, Hematopoietic Stem Cell Transplantation

Brief summary

The purpose of this study is to evaluate the efficacy of sorafenib for prophylaxis of leukemia relapse in allogeneic stem cell transplant (Allo-HSCT) recipients with FLT3-ITD positive acute myeloid leukemia (AML).

Detailed description

Internal tandem duplication of FMS-like tyrosine kinase 3 (FLT3-ITD) mutations have been reported in 20%-30% of patients with acute myeloid leukemia (AML). FLT3-ITD-positive AML patients have an inferior survival, primarily due to lower complete remission (CR) rate and higher relapse rate. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) improves the outcomes of some FLT3-ITD-positive AML, a significant number will suffer disease recurrence after allo-HSCT. Sorafenib, an inhibitor of multiple kinases including FLT3, has shown promising activity in FLT3-ITD-positive AML. Recent studies have shown that sorafenib monotherapy or in combination with chemotherapy are effective in attaining CR, but they do not have significant improvement in relapse. Currently, prophylactic use of sorafenib after allo-HSCT has been rarely reported, and whether it can improve outcomes of FLT3-ITD-positive AML remains unclear.

Qian Li, Xi Jia, Guopan Yu, Danian Nie, Ying Dong et al. (13 authors)

Blood2025-11-03

10.1182/blood-2025-1670

Sorafenib maintenance after allogeneic haemopoietic stem-cell transplantation in patients with FLT3-ITD acute myeloid leukaemia: long-term follow-up of an open-label, multicentre, randomised, phase 3 trial.

Xuan L, Wang Y, Yang K, Shao R, Huang F, Fan Z, Chi P, Xu Y, Xu N, Deng L, Li X, Liang X, Luo X, Shi P, Liu H, Wang Z, Jiang L, Lin R, Chen Y, Tu S, Zhang Y, Sun J, Huang X, Liu Q.

2023-07-0358 citations

10.1016/s2352-3026(23)00117-5

Effect of sorafenib maintenance on Epstein-Barr virus and cytomegalovirus infections in patients with FLT3-ITD AML undergoing allogeneic hematopoietic stem cell transplantation: a secondary analysis of a randomized clinical trial.

Xu X, Fan Z, Wang Y, Huang F, Xu Y, Sun J, Xu N, Deng L, Li X, Liang X, Luo X, Shi P, Liu H, Chen Y, Tu S, Huang X, Liu Q, Xuan L.

2022-09-025 citations

10.1186/s12916-022-02479-x

Sorafenib maintenance in patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised phase 3 trial.

Xuan L, Wang Y, Huang F, Fan Z, Xu Y, Sun J, Xu N, Deng L, Li X, Liang X, Luo X, Shi P, Liu H, Wang Z, Jiang L, Yu C, Zhou X, Lin R, Chen Y, Tu S, Huang X, Liu Q.

2020-08-10252 citations

10.1016/s1470-2045(20)30455-1

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).

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 60 Years

Healthy volunteers

No

Inclusion criteria

* FLT3-ITD Positive AML * Allo-HSCT Recipients

Exclusion criteria

* 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 (investigators' decision)

Design outcomes

Primary

Measure	Time frame
Incidence of leukemia relapse	1 year

Secondary

Measure	Time frame
Overall survival	3 year
leukemia-free survival	3 year
Incidence of side effect of sorafenib	6 months

Countries

China

Outcome results

None listed