New hope for AML patients who fail standard therapy: experimental combo trial launches

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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.