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

Acute Myeloid Leukemia Clinical Trial

Official title:

Sorafenib for Prophylaxis of Leukemia Relapse in Allogeneic Hematopoietic Stem Cell Transplant Recipients With FLT3-ITD Positive Acute Myeloid Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02474290
• Other study ID #: Sorafenib-Flt3 AML-2015
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: June 20, 2015
• Est. completion date: August 10, 2019

Study information

• Verified date: June 2015
• Source: Nanfang Hospital of Southern Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 202
• Est. completion date: August 10, 2019
• 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 (investigators' decision)

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• 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 (7)

Lead Sponsor	Collaborator
Nanfang Hospital of Southern Medical University	First People's Hospital of Chenzhou, Peking University People's Hospital, The First Affiliated Hospital of Guangzhou Medical University, Third Affiliated Hospital, Sun Yat-Sen University, Xiangya Hospital of Central South University, Zhujiang Hospital

Country where clinical trial is conducted

China, 

References & Publications (2)

Metzelder SK, Schroeder T, Finck A, Scholl S, Fey M, Götze K, Linn YC, Kröger M, Reiter A, Salih HR, Heinicke T, Stuhlmann R, Müller L, Giagounidis A, Meyer RG, Brugger W, Vöhringer M, Dreger P, Mori M, Basara N, Schäfer-Eckart K, Schultheis B, Baldus C, Neubauer A, Burchert A. High activity of sorafenib in FLT3-ITD-positive acute myeloid leukemia synergizes with allo-immune effects to induce sustained responses. Leukemia. 2012 Nov;26(11):2353-9. doi: 10.1038/leu.2012.105. Epub 2012 Apr 16. — View Citation

Ravandi F, Cortes JE, Jones D, Faderl S, Garcia-Manero G, Konopleva MY, O'Brien S, Estrov Z, Borthakur G, Thomas D, Pierce SR, Brandt M, Byrd A, Bekele BN, Pratz K, Luthra R, Levis M, Andreeff M, Kantarjian HM. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol. 2010 Apr 10;28(11):1856-62. doi: 10.1200/JCO.2009.25.4888. Epub 2010 Mar 8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of leukemia relapse		1 year
Secondary	Overall survival		3 year
Secondary	leukemia-free survival		3 year
Secondary	Incidence of side effect of sorafenib		6 months