Lisaftoclax Plus Azacitidine Maintenance After Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia Patients at High Risk of Relapse

Official title

Maintenance Therapy With Lisaftoclax Plus Azacitidine After Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia Patients at High Risk of Relapse: A Multicenter, Open-Label, Randomized Controlled Trial

Overview

This study evaluates the efficacy and safety of maintenance therapy with lisaftoclax plus azacitidine after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with acute myeloid leukemia (AML) at high risk of relapse. The main questions this study aims to answer are: * Does maintenance therapy with lisaftoclax plus azacitidine improve disease-free survival compared with observation alone after allo-HSCT? * Does maintenance therapy reduce relapse and improve overall survival? * What adverse events and safety outcomes are associated with this treatment strategy? Researchers will compare maintenance therapy with lisaftoclax plus azacitidine with observation or best supportive care in patients with AML at high risk of relapse following allo-HSCT. Participants will: * Be randomly assigned in a 2:1 ratio to receive either maintenance therapy with lisaftoclax plus azacitidine or observation. * Receive study treatment for up to 12 cycles or undergo observation according to the study assignment. * Undergo regular follow-up assessments, disease monitoring, and safety evaluations after transplantation.

Interventions

• Drug Lisaftoclax Plus Azacitidine
  Participants will receive maintenance therapy with lisaftoclax plus azacitidine after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Lisaftoclax will be administered orally at a dose of 400 mg once daily on Days 1-7 of each treatment cycle. Azacitidine will be administered at a dose of 32 mg/m² by subcutaneous injection or intravenous infusion on Days 1-5 of each treatment cycle. Each treatment cycle is 28 days in length. Maintenance therapy will be administered for up to 12 cyc

Primary outcome measures

• Disease-Free Survival [Time frame: 2 years]

Secondary outcome measures (5)

• Cumulative Incidence of Relapse [Time frame: 2 years]
• Overall Survival [Time frame: 2 years.]
• Cumulative Incidence of Pre-emptive Therapy. [Time frame: 2 years]
• Cumulative Incidence of Non-Relapse Mortality [Time frame: 2-years.]
• Treatment-Related Adverse Events [Time frame: From initiation of maintenance therapy to 30 days after last dose of study drug.]

Eligibility criteria

Inclusion criteria

Participants must meet all of the following criteria to be eligible for enrollment in this study:

• Diagnosed with acute myeloid leukemia (AML), excluding acute promyelocytic leukemia, according to the WHO 2022 classification, and without FLT3-ITD or FLT3-TKD mutations.
• Presence of at least one of the following high-risk features:

1\) Adverse-risk AML according to the ELN 2022 risk classification; 2) Refractory AML; 3) Relapsed AML; 4) Persistent measurable residual disease positivity prior to transplantation; 5) Secondary AML transformed from myelodysplastic syndrome or myeloproliferative neoplasm.

3\. Undergoing first allogeneic hematopoietic stem cell transplantation (allo-HSCT).

4\. Stable hematologic recovery, defined as: Absolute neutrophil count ≥ 1.0 × 10⁹/L without G-CSF support; and Platelet count ≥ 50 × 10⁹/L without platelet transfusion within 7 days prior to randomization.

5\. Age ≥18 years and ≤75 years. 6. Eastern Cooperative Oncology Group performance status of 0-2. 7. Ability to provide written informed consent before initiation of any study procedures.

8\. Written informed consent may be provided by the participant or an authorized immediate family member in accordance with local regulations.

Exclusion criteria

Participants meeting any of the following criteria will be excluded from the study:

• Evidence of disease relapse or impending relapse prior to randomization after transplantation, as determined by morphologic assessment or flow cytometry.
• Active or uncontrolled acute graft-versus-host disease (aGVHD) requiring systemic immunosuppressive therapy.
• Uncontrolled active infection requiring systemic antibacterial, antifungal, or antiviral therapy within 7 days prior to enrollment.
• Moderate or severe hepatic impairment, as defined by the Child-Pugh classification.
• Severe renal impairment, defined as creatinine clearance <30 mL/min (calculated using the Cockcroft-Gault formula) or requirement for dialysis.
• Pregnancy, or unwillingness/inability to use adequate contraception during the study treatment period.
• Psychiatric disorders or other medical conditions that, in the investigator's judgment, would interfere with compliance with study treatment, monitoring, or study procedures.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07686965 · IIT2026015

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗