Alternating Regimen of VA and Low-dose CHA in the Treatment of Unfit Newly Diagnosed AML

Inclusion Criteria:

* Understand the research and sign a written informed consent form;
* Be newly diagnosed with AML according to WHO 2022 criteria without prior treatment;
* or unwilling to undergo IC. Ineligibility for IC is defined as meeting any of the following criteria:
* Age ≥ 60 years
* Age 18-59 years but ineligible for intensive chemotherapy (IC) , meet ≥1 of the following:

  * Eastern Cooperative Oncology Group (ECOG) performance status ≥2 at screening;
  * Severe heart failure (congestive heart failure requiring treatment or myocardial infarction history with ejection fraction ≤50%);
  * Severe pulmonary dysfunction (DLCO ≤65%, FEV1 ≤65%, dyspnea at rest, or oxygen dependence);
  * Severe renal insufficiency requiring dialysis;
  * Child-Pugh B or C cirrhosis, or hepatic impairment with total bilirubin \>1.5×ULN;
* Mental illness requiring inpatient psychiatric treatment;
* Any comorbidity deemed by physician to contraindicate IC.

Exclusion Criteria:

* Diagnosis of: AML arising from chronic myeloid leukemia (CML); myeloid sarcoma; acute promyelocytic leukemia (APL) or presence of FLT3-ITD mutations;
* Active malignancies (except adequately treated carcinoma in situ or basal cell carcinoma) within 2 years prior to Cycle 1 Day 1 (C1D1);
* Major surgery or systemic anticancer therapy within 28 days before C1D1;
* Known hypersensitivity to: Active pharmaceutical ingredients: cladribine, homoharringtonine, cytarabine, venetoclax, azacitidine; Any excipients in study drug formulations;
* GI conditions impairing oral drug absorption: Dysphagia; short-gut syndrome; gastroparesis or related disorders;
* Uncontrolled active infection;
* Controlled infection permitted if: Afebrile (\<38°C) and hemodynamically stable (SBP \>90 mmHg, HR \<100 bpm) for ≥72 hours pre-C1D1; on non-interacting antimicrobial regimen; active HBV/HCV infection (Chronic carriers require PI approval with viral load monitoring); HIV-positive patients receiving HAART;
* Pregnancy/lactation or refusal of contraception: Negative serum β-hCG within 24h pre-C1D1;
* Psychiatric disorders or social circumstances compromising protocol compliance;
* Prior AML-directed therapy except: cytoreduction for hyperleukocytosis per institutional guidelines (hydroxyurea, leukapheresis); supportive growth factors;