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

Official 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

Overview

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).

Interventions

• 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.

Primary outcome measures

• Composite Complete Response Rate (CRc) [Time frame: Up to 2 cycles of LDH induction/consolidation therapy (approximately 56 days)]

Secondary outcome measures (6)

• Event-Free Survival (EFS) [Time frame: 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)]
• Overall Response Rate (ORR) [Time frame: 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)]
• Duration of Response (DOR) [Time frame: 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]

Eligibility criteria

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.

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The Second Affiliated Hospital, Zhejiang University School of Medicine — Hangzhou

Identifiers

NCT: NCT07505160 · 2026-0140

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗