Acute Myeloid Leukemia (AML)
Conditions
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).
Interventions
DRUGLisafotoclax
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.
DRUGDecitabine
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.
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.
Sponsors
Second Affiliated Hospital, School of Medicine, Zhejiang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite Complete Response Rate (CRc) | 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
| Measure | Time frame | Description |
|---|---|---|
| Event-Free Survival (EFS) | 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. |
| Complete Response Rate (CR) | 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. |
| Overall Response Rate (ORR) | 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. |
| Time to Response (TTR) | 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). |
| Duration of Response (DOR) | 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. |
| Overall Survival (OS) | Up to 12 months after the last patient is enrolled | The time from the first dose of study treatment to death from any cause. |
Countries
China
Contacts
CONTACTWenbin Qian
Outcome results
None listed