Influence of Co-existing Mutations on Sorafenib Maintenance Therapy After Allo-HSCT for Patients With FLT3-ITD AML

Acute Myeloid Leukemia Clinical Trial

Official title:

Influence of Co-existing Mutations on Sorafenib Maintenance Therapy After Allogeneic Hematopoietic Stem Cell Transplantation for Patients With FLT3-ITD Positive Acute Myeloid Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04788420
• Other study ID #: Sorafenib-Flt3 AML-2020
• Status: Completed
• Start date: January 1, 2012
• Est. completion date: December 31, 2020

Study information

• Verified date: May 2022
• Source: Nanfang Hospital of Southern Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to reveal the influence of co-existing mutations on the efficacy of sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for patients with FLT3-ITD AML.

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. Our previous studies demonstrated that post-transplantation sorafenib maintenance could improve the outcomes of FLT3-ITD-positive AML patients. However, whether other co-existing mutations influence the efficacy of post-allo-HSCT sorafenib maintenance remains unknown.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 456
• Est. completion date: December 31, 2020
• Est. primary completion date: July 21, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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 (according to the investigators' decision)

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Acute Myeloid Leukemia With FLT3/ITD Mutation
• Hematopoietic Stem Cell Transplantation
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Sorafenib
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).

Locations

Country	Name	City	State
China	Department of Hematology,Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong

Sponsors (11)

Lead Sponsor

Collaborator

Nanfang Hospital of Southern Medical University

First Affiliated Hospital of Zhejiang University, First People's Hospital of Chenzhou, Institute of Hematology & Blood Diseases Hospital, Peking University People's Hospital, The First Affiliated Hospital of Guangzhou Medical University, The First Affiliated Hospital of Soochow University, Third Affiliated Hospital, Sun Yat-Sen University, Xiangya Hospital of Central South University, Xinqiao Hospital of Chongqing, Zhujiang Hospital

Country where clinical trial is conducted

China, 

References & Publications (4)

Shi J, Cao L, Luo Y, Zhao Y, Tan Y, Yu J, Lai X, Zhu Y, Hu Y, He J, Sun J, Zheng W, Wei G, Huang H. Maintenance sorafenib is superior to prophylactic donor lymphocyte infusion at improving the prognosis of acute myeloid leukemia with FMS-like tyrosine kinase 3 internal tandem duplication after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2021 Jan;56(1):293-296. doi: 10.1038/s41409-020-01015-w. Epub 2020 Aug 4. — View Citation

Xuan L, Wang Y, Chen J, Jiang E, Gao L, Wu B, Deng L, Liang X, Huang F, Fan Z, Tang X, Sun J, Zhang X, Han M, Wu D, Huang X, Liu Q. Sorafenib Therapy Is Associated with Improved Outcomes for FMS-like Tyrosine Kinase 3 Internal Tandem Duplication Acute Myeloid Leukemia Relapsing after Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2019 Aug;25(8):1674-1681. doi: 10.1016/j.bbmt.2019.04.018. Epub 2019 Apr 19. — View Citation

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. Sorafenib maintenance in patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised phase 3 trial. Lancet Oncol. 2020 Sep;21(9):1201-1212. doi: 10.1016/S1470-2045(20)30455-1. Epub 2020 Aug 10. — View Citation

Xuan L, Wang Y, Huang F, Jiang E, Deng L, Wu B, Fan Z, Liang X, Xu N, Ye J, Lin R, Yin C, Zhang Y, Sun J, Han M, Huang X, Liu Q. Effect of sorafenib on the outcomes of patients with FLT3-ITD acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation. Cancer. 2018 May 1;124(9):1954-1963. doi: 10.1002/cncr.31295. Epub 2018 Mar 6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of leukemia relapse		2 year
Secondary	Overall survival		2 year
Secondary	Leukemia-free survival		2 year