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

• ClinicalTrials.gov Identifier: NCT02474290
• Recruitment Status: Completed
• First Posted: June 17, 2015
• Last Update Posted: August 26, 2019
• Sponsor: Nanfang Hospital, Southern Medical University
• Collaborators: Peking University People's Hospital; Third Affiliated Hospital, Sun Yat-Sen University; Zhujiang Hospital; Xiangya Hospital of Central South University; First People's Hospital of Chenzhou; The First Affiliated Hospital of Guangzhou Medical University
• Information provided by (Responsible Party): Qifa Liu, Nanfang Hospital, Southern Medical University

Tracking Information

• First Submitted Date: June 14, 2015
• First Posted Date: June 17, 2015
• Last Update Posted Date: August 26, 2019
• Actual Study Start Date: June 20, 2015
• Actual Primary Completion Date: July 21, 2018 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 14, 2015): Incidence of leukemia relapse [ Time Frame: 1 year ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 14, 2015)

• Overall survival [ Time Frame: 3 year ]
• leukemia-free survival [ Time Frame: 3 year ]
• Incidence of side effect of sorafenib [ Time Frame: 6 months ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Sorafenib for Prophylaxis of Leukemia Relapse in Allo-HSCT Recipients With FLT3-ITD Positive AML
• Official Title: Sorafenib for Prophylaxis of Leukemia Relapse in Allogeneic Hematopoietic Stem Cell Transplant Recipients With FLT3-ITD Positive Acute Myeloid Leukemia
• 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.
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Acute Myeloid Leukemia
• Hematopoietic Stem Cell Transplantation

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).

Study Arms

• Experimental: Sorafenib group
  Sorafenib will be used from day 30 to 180 post-transplantation.
  Intervention: Drug: Sorafenib
• No Intervention: non-Sorafenib group

Publications *

• 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.
• Metzelder SK, Schroeder T, Finck A, Scholl S, Fey M, Gotze K, Linn YC, Kroger M, Reiter A, Salih HR, Heinicke T, Stuhlmann R, Muller L, Giagounidis A, Meyer RG, Brugger W, Vohringer M, Dreger P, Mori M, Basara N, Schafer-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.
• 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. 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. BMC Med. 2022 Sep 2;20(1):282. doi: 10.1186/s12916-022-02479-x.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 21, 2019): 202
• Original Estimated Enrollment (submitted: June 14, 2015): 200
• Actual Study Completion Date: August 10, 2019
• Actual Primary Completion Date: July 21, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT02474290
• Other Study ID Numbers: Sorafenib-Flt3 AML-2015
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Qifa Liu, Nanfang Hospital, Southern Medical University
• Original Responsible Party: Same as current
• Current Study Sponsor: Nanfang Hospital, Southern Medical University
• Original Study Sponsor: Same as current

Collaborators

• Peking University People's Hospital
• Third Affiliated Hospital, Sun Yat-Sen University
• Zhujiang Hospital
• Xiangya Hospital of Central South University
• First People's Hospital of Chenzhou
• The First Affiliated Hospital of Guangzhou Medical University

Investigators

• Principal Investigator: Qifa Liu; Nanfang Hospital, Southern Medical University

• PRS Account: Nanfang Hospital, Southern Medical University
• Verification Date: June 2015