Mitoxantrone Hydrochloride Liposome, Cytarabine, G-CSF Plus Venetoclax vs. Azacitidine Plus Venetoclax for MDS-IB2 and Secondary/Elderly AML

Inclusion Criteria:

• 1. The patient fully understands the study, voluntarily participates, and signs the Informed Consent Form (ICF).

  2. Age: 18-75 years inclusive. 3. Patients with clinically confirmed adult AML or MDS-IB2 (according to WHO 2022 criteria or ICC 2022 criteria). AML patients must meet any of the following:

  1. Therapy-related AML
  2. Prior history of MDS
  3. Presence of MDS-related genetic/chromosomal abnormalities
  4. Prior history of CMML
  5. Age ≥ 60 years

  6. Prior history of antecedent MPN (including ET, PV, and MF) with bone marrow fibrosis ≤ grade 2 (on a 0-3 grade scale) 4. For elderly AML patients, comprehensive assessment must show they belong to the Fit population: ECOG < 3, CCI ≤ 0, and MMSE and SPPB assessment results meeting the Fit population criteria.

     5. Liver and kidney function: ALT and AST ≤ 2.5 × ULN (≤ 5 × ULN for patients with liver infiltration); total bilirubin ≤ 1.5 × ULN (≤ 3 × ULN for patients with liver infiltration); serum creatinine ≤ 1.5 × ULN.

     6. Expected survival ≥ 3 months. 7. Prior MDS-related therapy (excluding blood transfusions) must be completed at least 2 weeks before the start of study treatment. In cases of rapidly proliferative disease, hydroxyurea is permitted up to 24 hours before the start of study treatment. Toxicities from prior MDS therapy must have recovered to Grade 2 or lower before the start of study treatment.

     Exclusion Criteria:

• Patients who meet any of the following criteria will be excluded from the study:

  1. Prior anti-cancer treatment history meeting any of the following:

     1. Prior treatment with mitoxantrone or mitoxantrone liposome.
     2. Prior treatment with venetoclax or hypomethylating agents.
     3. Prior treatment with doxorubicin or other anthracyclines, with a cumulative doxorubicin dose > 360 mg/m^2 (for other anthracyclines, 1 mg doxorubicin is equivalent to 2 mg daunorubicin or 0.5 mg idarubicin).
     4. Received anti-cancer treatment including surgery, chemotherapy, targeted therapy, etc., or participated in another clinical trial with investigational drug within 4 weeks or 5 half-lives before the first dose of study drug.

  2. Cardiac function or disease meeting any of the following:

     1. Long QTc syndrome or QTc interval > 480 ms.
     2. Complete left bundle branch block, second-degree or third-degree atrioventricular block.
     3. Severe, uncontrolled arrhythmia requiring medication.
     4. New York Heart Association (NYHA) Class ≥ II.
     5. Left ventricular ejection fraction (LVEF) < 50%.
     6. History of myocardial infarction, unstable angina, severe unstable ventricular arrhythmia or any other arrhythmia requiring treatment, clinically significant pericardial disease within 6 months before enrollment, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
  3. Concurrent uncontrolled malignancy other than adequately controlled non-melanoma skin basal cell carcinoma, carcinoma in situ of breast/cervix, or other malignancies that have been effectively controlled without treatment for > 6 months and patients receiving long-term non-chemotherapy treatment (e.g., hormone therapy).
  4. Uncontrolled systemic disease (e.g., progressive infection, uncontrolled hypertension, diabetes mellitus).
  5. Central nervous system (CNS) leukemia.
  6. Secondary AML with bone marrow fibrosis ≥ grade 3.
  7. Blast crisis of chronic myeloid leukemia (CML).
  8. AML with favorable-risk karyotypes: t(8;21)(q22;q22.1) RUNX1::RUNX1T1, inv(16)(p13.1q22) CBFB::MYH11, or acute promyelocytic leukemia (APL).
  9. Human immunodeficiency virus (HIV) infection (HIV antibody positive).
  10. Active hepatitis B or hepatitis C infection (HBsAg or HBcAb positive with HBV-DNA > 1×10^3 copies/mL; HCV antibody positive with HCV-RNA > 1×10^3 copies/mL).
  11. Known immediate or delayed hypersensitivity reaction to the study drug's class or excipients.