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).
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.
VA intolerance: Treatment discontinuation due to ≥Grade 3 non-hematologic toxicity or persistent ≥Grade 4 hematologic toxicity;
Primary resistance: No partial remission (PR) after 1-2 cycles of VA induction therapy;
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.
Single group
Lisafotoclax
DrugOral 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.
Decitabine
DrugIntravenous 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
DrugIntraversible 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.
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.
Event-Free Survival (EFS)
The time from the first dose of study treatment to the first occurrence of disease progression, relapse, or death from any cause.
Complete Response Rate (CR)
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.
Overall Response Rate (ORR)
The proportion of participants who achieve any response (CR + CRi + MLFS + partial remission \[PR\]) after 1-2 cycles of LDH induction/consolidation therapy.
Time to Response (TTR)
The time from the first dose of study treatment to the first documentation of any response (CR, CRi, MLFS, or PR).
Minimal Residual Disease (MRD) Negative Rate
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.
Rate of Bridging to Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT)
The proportion of participants who proceed to allogeneic hematopoietic stem cell transplantation after achieving MRD-negative status with LDH induction/consolidation therapy.
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