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

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

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

Study Overview

• Status: Recruiting
• Conditions: Acute Leukemia; Hematopoietic Stem Cell Transplantation; Relapse
• Intervention / Treatment: Drug: Sorafenib

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 Type: Interventional
• Enrollment (Anticipated): 346
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Department of Hematology,Nanfang Hospital, Southern Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of leukemia relapse	1 year

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Nanfang Hospital of Southern Medical University
• Collaborators: Xiangya Hospital of Central South University; Peking University People's Hospital; Second Affiliated Hospital, Sun Yat-Sen University; The Third Xiangya Hospital of Central South University; The First Affiliated Hospital of Guangzhou Medical University; Zhujiang Hospital; Third Affiliated Hospital, Sun Yat-Sen University; First People's Hospital of Chenzhou; The Seventh Affiliated Hospital of Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2020
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: December 14, 2020
• First Submitted That Met QC Criteria: December 14, 2020
• First Posted (Actual): December 19, 2020

Study Record Updates

• Last Update Posted (Actual): November 8, 2021
• Last Update Submitted That Met QC Criteria: October 30, 2021
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Sorafenib; Relapse; Acute Leukemia; Allogeneic hematopoietic stem cell transplantation; FLT3-negative
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Leukemia; Recurrence; Acute Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: Sorafenib-Non-Flt3 AL-2020

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No