Clinical trial NCT04674345: Sorafenib Maintenance for Prophylaxis of Leukemia Relapse in Allo-HSCT Recipients With FLT3 Negative Acute Leukemia
Official title: Sorafenib Maintenance for Prophylaxis of Leukemia Relapse in Allogeneic Hematopoietic Stem Cell Transplant Recipients With FLT3 Negative Acute Leukemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Acute Leukemia
Relapse
Hematopoietic Stem Cell Transplantation
Keywords: Acute Leukemia
Sorafenib
Relapse
FLT3-negative
Allogeneic hematopoietic stem cell transplantation
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
Collaborators: name: Peking University People's Hospital
name: Xiangya Hospital of Central South University
name: Zhujiang Hospital
name: Third Affiliated Hospital, Sun Yat-Sen University
name: First People's Hospital of Chenzhou
name: The First Affiliated Hospital of Guangzhou Medical University
name: The Third Xiangya Hospital of Central South University
name: Second Affiliated Hospital, Sun Yat-Sen University
name: The Seventh Affiliated Hospital of Sun Yat-sen University
First posted: 2020-12-19
Enrollment: 346
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Incidence of leukemia relapse
timeFrame: 1 year
Secondary outcomes:
measure: Overall survival
timeFrame: 1 year
measure: Leukemia-free survival
timeFrame: 1 year
measure: Adverse effects
timeFrame: 1 year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Department of Hematology,Nanfang Hospital, Southern Medical University
state: Guangdong
Study officials:
affiliation: Nanfang Hospital, Southern Medical University
name: Qifa Liu
role: PRINCIPAL_INVESTIGATOR
References: