Sorafenib Maintenance for Prophylaxis of Leukemia Relapse in Allo-HSCT Recipients With FLT3 Negative Acute Leukemia

Sponsor

Nanfang Hospital of Southern Medical University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04674345

Collaborator

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

346

Enrollment

Location

Arms

36.5

Anticipated Duration (Months)

9.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of sorafenib maintenance after allo-HSCT in FLT3-negative acute leukemia patients.

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

Detailed Description

Sorafenib is a multikinase inhibitor that blocks multiple pathways involved in the development and progression of acute leukemia, such as FLT3-ITD, the RAS and RAF gene families, KIT, and the VEGF and PDGF receptors. Recently, two back-to-back randomized controlled trials both reveal that sorafenib maintenance after allo-HSCT could prevent relapse in patients with FLT3-ITD AML, resulting in a survival benefit. Sorafenib has also been explored in the treatment of acute leukemia without FLT3 mutations and shown promising results. Currently, relapse remains the major cause of transplant failure, especially for high-risk and refractory acute leukemia patients. Once patients relapse after allo-HSCT, the prognosis is dismal. Therefore, prevention of relapse is of great importance to improve the prognosis. Based on the current research status, we plan to conduct a prospective, multicenter, phase 2 randomized controlled trial to explore the efficacy and safety of sorafenib maintenance after allo-HSCT in FLT3-negative acute leukemia patients.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

346 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Sorafenib Maintenance for Prophylaxis of Leukemia Relapse in Allogeneic Hematopoietic Stem Cell Transplant Recipients With FLT3 Negative Acute Leukemia

Actual Study Start Date :

Dec 15, 2020

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sorafenib group Sorafenib will be administered at 45-60 days post-transplantation and taken for one year.	Drug: Sorafenib The initial dose of sorafenib is 400 mg orally twice daily and is adjusted in case of suspected toxicity (dose range, 200-800 mg daily).
No Intervention: Non-maintenance group Neither sorafenib nor other FLT3 inhibitors will be used, unless the patient experiences relapse.

Arm

Intervention/Treatment

Experimental: Sorafenib group

Sorafenib will be administered at 45-60 days post-transplantation and taken for one year.

Drug: Sorafenib

The initial dose of sorafenib is 400 mg orally twice daily and is adjusted in case of suspected toxicity (dose range, 200-800 mg daily).

No Intervention: Non-maintenance group

Neither sorafenib nor other FLT3 inhibitors will be used, unless the patient experiences relapse.

Outcome Measures

Primary Outcome Measures

Incidence of leukemia relapse [1 year]

Secondary Outcome Measures

Overall survival [1 year]
Leukemia-free survival [1 year]
Adverse effects [1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with FLT3-negative acute leukemia undergoing first allo-HSCT
Age 18 to 65 years old with ECOG performance status 0-2
Hematopoietic recovery within 60 days post-transplantation
Sign informed consent form, have the ability to comply with study and follow-up procedures

Exclusion Criteria:

Acute promyelocytic leukemia (AML subtype M3)
Acute leukemia with FLT3-ITD or FLT3-TKD mutations
Philadelphia-positive acute lymphoblastic leukemia
Chronic myelogenous leukemia with blast crisis
Intolerance to sorafenib pre-transplantation
Life expectancy less than 30 days post-transplantation
Active aGVHD or uncontrolled infections within 60 days post-transplantation
Cardiac dysfunction (particularly congestive heart failure, unstable coronary artery disease and serious cardiac ventricular arrhythmias requiring antiarrhythmic therapy)
Respiratory failure ( PaO2 ≤60mmHg)
Hepatic abnormalities (total bilirubin ≥3 mg/dL, aminotransferase >2 times the upper limit of normal)
Renal dysfunction (creatinine clearance rate < 30 mL/min)
ECOG performance status 3, 4 or 5
With any conditions not suitable for the trial (investigators' decision)