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

Study Overview
=================
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.

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.

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

Conditions
-----------------
Acute Leukemia, Relapse, Hematopoietic Stem Cell Transplantation

Intervention / Treatment
-----------------
* Drug: Sorafenib


Participation Criteria
=================
Eligibility Criteria
-----------------
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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sorafenib group<br>Sorafenib will be administered at 45-60 days post-transplantation and taken for one year. | Drug: Sorafenib<br>* 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).<br>|
| No Intervention: Non-maintenance group<br>Neither sorafenib nor other FLT3 inhibitors will be used, unless the patient experiences relapse. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of leukemia relapse |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 1 year | 
| Leukemia-free survival |  | 1 year | 
| Adverse effects |  | 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Acute Leukemia, Sorafenib, Relapse, FLT3-negative, Allogeneic hematopoietic stem cell transplantation