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

NCT07505160 | Not Yet Recruiting Phase 2

• 1 other identifier: 2026-0140
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Acute Myeloid Leukemia (AML)

Outcome Measures

Primary Outcomes (1)

• Composite Complete Response Rate (CRc)

  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 Outcomes (6)

• Event-Free Survival (EFS)

  Up to 12 months after the last patient is enrolled

• Complete Response Rate (CR)

  Up to 2 cycles of LDH therapy (approximately 56 days)

• Overall Response Rate (ORR)

  Up to 2 cycles of LDH therapy (approximately 56 days)

• Time to Response (TTR)

  Up to 2 cycles of LDH therapy (approximately 56 days)

• Duration of Response (DOR)

  Up to 12 months after the last patient is enrolled

Other Outcomes (2)

• Minimal Residual Disease (MRD) Negative Rate

  Up to 2 cycles of LDH therapy (approximately 56 days)

• Rate of Bridging to Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT)

  Up to 3 months after achieving MRD negativity

Study Arms (1)

Lisafotoclax + Decitabine + Homoharringtonine (LDH) Treatment Arm

EXPERIMENTAL

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; Drug: Decitabine; Drug: Homoharringtonine

Interventions

Lisafotoclax DRUG

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.

Lisafotoclax + Decitabine + Homoharringtonine (LDH) Treatment Arm

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.

Lisafotoclax + Decitabine + Homoharringtonine (LDH) Treatment Arm

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.

Lisafotoclax + Decitabine + Homoharringtonine (LDH) Treatment Arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

The Second Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310009, China

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Decitabine; Homoharringtonine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Harringtonines; Alkaloids; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 4 or More Rings

Central Study Contacts

Wenbin Qian

CONTACT

+86-0571-87783777; qianwb@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2026
• First Posted: April 1, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2029
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)