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

Sponsor

Nanfang Hospital of Southern Medical University (Other)

Overall Status

Completed

CT.gov ID

NCT02474290

Collaborator

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

202

Enrollment

Location

Arms

49.7

Actual Duration (Months)

4.1

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Hematopoietic Stem Cell Transplantation	Drug: Sorafenib	Phase 2/Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

202 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 20, 2015

Actual Primary Completion Date :

Jul 21, 2018

Actual Study Completion Date :

Aug 10, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sorafenib group Sorafenib will be used from day 30 to 180 post-transplantation.	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).
No Intervention: non-Sorafenib group

Arm

Intervention/Treatment

Experimental: Sorafenib group

Sorafenib will be used from day 30 to 180 post-transplantation.

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).

No Intervention: non-Sorafenib group

Outcome Measures

Primary Outcome Measures

Incidence of leukemia relapse [1 year]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)