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

Prior treatment

• 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;
• 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;
• Prior AML-directed therapy except: cytoreduction for hyperleukocytosis per institutional guidelines (hydroxyurea, leukapheresis); supportive growth factors;

Other illness

• 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;
• Psychiatric disorders or social circumstances compromising protocol compliance;

Lab values

• Pregnancy/lactation or refusal of contraception: Negative serum β-hCG within 24h pre-C1D1;

Other

• Diagnosis of: AML arising from chronic myeloid leukemia (CML); myeloid sarcoma; acute promyelocytic leukemia (APL) or presence of FLT3-ITD mutations;

• 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.