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NCT Number: NCT07505160

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

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).

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Key information

Conditions

Acute Myeloid Leukemia (AML) Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Neoplasms Neoplasms by Histologic Type

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

The Second Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310009, China

Location contact

Wenbin Qian

CONTACT

[email protected]

+86-0571-87783777

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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:
  • VA intolerance: Treatment discontinuation due to ≥Grade 3 non-hematologic toxicity or persistent ≥Grade 4 hematologic toxicity;
  • 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.

Treatment and study plan

Lisafotoclax

Drug

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

  • 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.
  • LD maintenance phase (28-day cycles): 600 mg once daily on days 1-14.

decitabine

Drug

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.

Homoharringtonine

Drug

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.

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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).

  5. 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.

  6. 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.

Other outcomes

  1. 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.

  2. 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Wenbin Qian

CONTACT

[email protected]

+86-0571-87783777

Sponsors and collaborators

Lead sponsor

Second Affiliated Hospital, School of Medicine, Zhejiang University

Other

Registry information

Official study title

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

Important dates

Study start
2026
Primary completion
2028
Study completion
2029
First posted
Apr 1, 2026
Registry last updated
Apr 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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