Efficacy and Safety of Lisafotoclax Plus Decitabine and Homoharringtonine in Venetoclax/Azacitidine Pretreated AML Patients

March 26, 2026 updated by: Second Affiliated Hospital, School of Medicine, Zhejiang University

A Multi-Center, Prospective, Single-Arm, Phase 2 Clinical Study on the Efficacy and Safety of Lisafotoclax Combined With Decitabine and Homoharringtonine in Patients With Acute Myeloid Leukemia Previously Treated With Venetoclax Combined With Azacitidine Regimen

This is a multi-center, prospective, single-arm, phase 2 clinical study conducted in China to evaluate the efficacy and safety of Lisafotoclax combined with Decitabine and Homoharringtonine in patients with acute myeloid leukemia (AML) who have failed or are intolerant to prior treatment with Venetoclax plus Azacitidine.

Eligible participants must be at least 18 years old, have a confirmed diagnosis of AML according to WHO 2016 criteria, and have an ECOG performance status of 0-2. Participants will receive oral Lisafotoclax in combination with intravenous Decitabine and Homoharringtonine according to the study protocol.

The primary objective is to assess the overall response rate (ORR) after induction treatment. Secondary objectives include evaluating complete remission (CR) rate, event-free survival (EFS), overall survival (OS), and the incidence of adverse events (AEs) and serious adverse events (SAEs). Participants will be followed for up to 12 months after the last patient is enrolled to collect long-term efficacy and safety data.

This study has been approved by the Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine and will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice (GCP).

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

35

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310009
        • The Second Affiliated Hospital, Zhejiang University School of Medicine
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  • Age ≥18 years old.
  • Diagnosis of acute myeloid leukemia (AML), not otherwise specified (non-acute promyelocytic leukemia [APL]), confirmed by WHO 2022 5th edition criteria.

  • Evidence of treatment failure after prior venetoclax + azacitidine (VA) regimen, defined as either:

    1. VA intolerance: Treatment discontinuation due to ≥Grade 3 non-hematologic toxicity or persistent ≥Grade 4 hematologic toxicity;
    2. VA treatment failure:
  • Primary resistance: No partial remission (PR) after 1-2 cycles of VA induction therapy;
  • Molecular persistence/progression: ≥1 log increase or persistent positivity of driver gene mutations (e.g., FLT3-ITD, IDH1/2, NPM1) by quantitative PCR or NGS compared to best response;
  • Hematologic relapse: ≥5% bone marrow blasts or extramedullary leukemia after prior CR/CRi.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
  • Adequate organ function within 7 days prior to study initiation:
  • Liver: Total bilirubin ≤1.5×ULN; AST/ALT ≤2.5×ULN;
  • Kidney: Serum creatinine ≤1.5×ULN or CrCl ≥50 mL/min;
  • Heart: Left ventricular ejection fraction (LVEF) ≥50%.
  • Ability to provide written informed consent and comply with study procedures. Exclusion Criteria
  • Diagnosis of acute promyelocytic leukemia (APL) or Philadelphia chromosome-positive AML.
  • Prior treatment with any BCL-2 inhibitor other than venetoclax as part of VA regimen.
  • Active central nervous system (CNS) leukemia involvement.
  • Uncontrolled systemic active infection.
  • Known HIV infection, or active hepatitis B or C.
  • New York Heart Association (NYHA) Class III-IV heart failure, unstable angina, myocardial infarction within 6 months, or severe arrhythmia.
  • Other active uncontrolled malignancy.
  • Severe gastrointestinal disease affecting drug absorption.
  • Pregnant or breastfeeding individuals; fertile patients refusing effective contraception during study and 6 months after last dose.
  • Known hypersensitivity to any component of LDH or LD regimens.
  • Any other condition judged by investigator to interfere with study conduct or patient safety.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Lisafotoclax + Decitabine + Homoharringtonine (LDH) Treatment Arm
All participants receive LDH regimen (induction/consolidation) followed by LD regimen maintenance per study protocol, with or without allogeneic hematopoietic stem cell transplantation based on MRD status and fitness.
Drug: Lisafotoclax

Oral investigational BCL-2 inhibitor, administered in two phases:

  1. LDH induction/consolidation phase (28-day cycles):

    • Cycle 1: 200 mg on day 1, 400 mg on day 2, 600 mg on days 3-28;
    • Cycle 2 and beyond: 600 mg once daily on days 1-28.
  2. LD maintenance phase (28-day cycles): 600 mg once daily on days 1-14.
Drug: Decitabine
Intravenous hypomethylating agent, administered at 15 mg/m²/day via intravenous infusion over 3 hours on days 1-3 of each 28-day cycle, used in both LDH induction/consolidation and LD maintenance regimens.
Drug: Homoharringtonine
Intraversible alkaloid anti-leukemia agent, administered at 1 mg/m²/day via intravenous infusion over 2 hours on days 1-7 of each 28-day cycle, used exclusively in the LDH induction/consolidation phase of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite Complete Response Rate (CRc)
Time Frame: Up to 2 cycles of LDH induction/consolidation therapy (approximately 56 days)
The proportion of participants who achieve composite complete remission (CRc), defined as the combination of complete remission (CR), complete remission with incomplete hematologic recovery (CRi), and morphologic leukemia-free state (MLFS) after 1-2 cycles of LDH induction/consolidation therapy.
Up to 2 cycles of LDH induction/consolidation therapy (approximately 56 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-Free Survival (EFS)
Time Frame: Up to 12 months after the last patient is enrolled
The time from the first dose of study treatment to the first occurrence of disease progression, relapse, or death from any cause.
Up to 12 months after the last patient is enrolled
Complete Response Rate (CR)
Time Frame: Up to 2 cycles of LDH therapy (approximately 56 days)
The proportion of participants who achieve complete remission (CR), defined as <5% bone marrow blasts, no evidence of extramedullary disease, and recovery of peripheral blood counts (ANC ≥1.0×10⁹/L, platelets ≥100×10⁹/L) after 1-2 cycles of LDH therapy.
Up to 2 cycles of LDH therapy (approximately 56 days)
Overall Response Rate (ORR)
Time Frame: Up to 2 cycles of LDH therapy (approximately 56 days)
The proportion of participants who achieve any response (CR + CRi + MLFS + partial remission [PR]) after 1-2 cycles of LDH induction/consolidation therapy.
Up to 2 cycles of LDH therapy (approximately 56 days)
Time to Response (TTR)
Time Frame: Up to 2 cycles of LDH therapy (approximately 56 days)
The time from the first dose of study treatment to the first documentation of any response (CR, CRi, MLFS, or PR).
Up to 2 cycles of LDH therapy (approximately 56 days)
Duration of Response (DOR)
Time Frame: Up to 12 months after the last patient is enrolled
The time from the first documentation of response (CR, CRi, MLFS, or PR) to the first occurrence of disease progression, relapse, or death from any cause.
Up to 12 months after the last patient is enrolled
Overall Survival (OS)
Time Frame: Up to 12 months after the last patient is enrolled
The time from the first dose of study treatment to death from any cause.
Up to 12 months after the last patient is enrolled

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Minimal Residual Disease (MRD) Negative Rate
Time Frame: Up to 2 cycles of LDH therapy (approximately 56 days)
The proportion of participants who achieve undetectable MRD in bone marrow (by flow cytometry or molecular testing) after 1-2 cycles of LDH induction/consolidation therapy.
Up to 2 cycles of LDH therapy (approximately 56 days)
Rate of Bridging to Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT)
Time Frame: Up to 3 months after achieving MRD negativity
The proportion of participants who proceed to allogeneic hematopoietic stem cell transplantation after achieving MRD-negative status with LDH induction/consolidation therapy.
Up to 3 months after achieving MRD negativity

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 1, 2026

Primary Completion (Estimated)

March 1, 2028

Study Completion (Estimated)

March 1, 2029

Study Registration Dates

First Submitted

March 26, 2026

First Submitted That Met QC Criteria

March 26, 2026

First Posted (Actual)

April 1, 2026

Study Record Updates

Last Update Posted (Actual)

April 1, 2026

Last Update Submitted That Met QC Criteria

March 26, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2026-0140

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Acute Myeloid Leukemia (AML)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Jordan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe