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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Myeloid Leukemia (AML); Hematopoetic Stem Cell Transplantation; Maintenance Treatment
• Intervention / Treatment: Drug: Lisaftoclax Plus Azacitidine

• Study Type: Interventional
• Enrollment (Estimated): 191
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

1. Diagnosed with acute myeloid leukemia (AML), excluding acute promyelocytic leukemia, according to the WHO 2022 classification, and without FLT3-ITD or FLT3-TKD mutations.
2. 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:

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

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
No Intervention: Observation
Experimental: Lisaftoclax plus Azacitidine Maintenance Therapy	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 cycles or until 15 months after allo-HSCT, whichever occurs first. The dose of lisaftoclax may be modified according to concomitant medications and treatment-related hematologic toxicities. The interval between treatment cycles may be extended based on individual tolerability and hematologic recovery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-Free Survival	Disease status (including relapse) and survival outcomes will be evaluated for the assessment of disease-free survival (DFS). DFS is defined as the time from randomization to the first occurrence of relapse or death from any cause. Prespecified subgroup analyses will be conducted according to pre-transplant measurable residual disease (MRD) status (MRD-positive vs. MRD-negative) to assess the consistency of treatment effects across MRD subgroups.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Incidence of Relapse	The cumulative incidence of relapse will be assessed during the follow-up period.	2 years
Overall Survival	Overall survival (OS) is defined as the time from randomization to death from any cause. Prespecified subgroup analyses will be conducted according to pre-transplant measurable residual disease (MRD) status to assess the consistency of treatment effects between MRD-positive and MRD-negative patients.	2 years.
Cumulative Incidence of Pre-emptive Therapy.	Pre-emptive therapy rate is defined as the proportion of patients who receive additional anti-leukemic treatment triggered by measurable residual disease positivity or other molecular evidence of impending relapse after allogeneic hematopoietic stem cell transplantation.	2 years
Cumulative Incidence of Non-Relapse Mortality	Non-relapse mortality, defined as death without prior disease relapse or progression, assessed as a cumulative incidence.	2-years.
Treatment-Related Adverse Events	Incidence, severity, and type of adverse events will be evaluated and graded according to CTCAE v5.0 during maintenance therapy and follow-up.	From initiation of maintenance therapy to 30 days after last dose of study drug.

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Estimated): August 10, 2026
• Primary Completion (Estimated): August 10, 2030
• Study Completion (Estimated): August 10, 2030

Study Registration Dates

• First Submitted: June 30, 2026
• First Submitted That Met QC Criteria: June 30, 2026
• First Posted (Actual): July 7, 2026

Study Record Updates

• Last Update Posted (Actual): July 7, 2026
• Last Update Submitted That Met QC Criteria: June 30, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine; Lisaftoclax
• Other Study ID Numbers: IIT2026015

Drug and device information, study documents

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