A Bridging Study of Liposomal Cytarabine-Daunorubicin in Treating Olderly Patients With Treatment-naive High-Risk (Secondary) Acute Myeloid Leukemia

Liposomal cytarabine-daunorubicin for injection manufactured by CSPC Zhongnuo Pharmaceutical Technology Co., Ltd is a class 3 chemical drug imitating Vyxeos developed by Jazz Pharmaceuticals plc. This bridging trial compares the efficacy of liposomal cytarabine-daunorubicin for injection manufactured by CSPC Zhongnuo Pharmaceutical Technology Co., Ltd with cytarabine/daunorubicin (7+3) in elderly patients with treatment-naïve high-risk (secondary) AML to determine that test drug is comparable to Vyxeos in efficacy, safety and pharmacokinetic properties. Patients will be randomized in a 1:1 ratio to receive liposomal cytarabine-daunorubicin or daunorubicin/cytarabine as induction and consolidation chemotherapy. Patients will receive up to two cycles of induction and consolidation therapy. After the treatment period, there is a follow-up phase for overall survival.

Inclusion criteria

• Able to understand the study and voluntarily sign informed consent.
• Male or female between 60-75 years of age (inclusive).
• Pathological diagnosis of AML according to 2022 WHO criteria (with at least 20% blasts in the peripheral blood or bone marrow) and fulfill of one of the following standards:

• Therapy related AML: t-AML must have a documented history of prior cytotoxic therapy or ionizing radiotherapy for an unrelated disease;
• AML with a history of myelodysplasia: MDSAML must have bone marrow documentation of prior MDS;
• AML with a history of CMMoL: CMMoLAML must have bone marrow documentation of prior CMMoL;
• De novo AML with karyotypic abnormalities characteristic of MDS: de novoAML must have cytogenetics with abnormalities per WHO.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Laboratory values meet the following criteria:

• Serum creatinine≤2 × ULN;
• Serum total bilirubin≤2 × ULN, ≤3 × ULN for patients with liver involvement;
• Serum alanine aminotransferase or aspartate aminotransferase≤3 × ULN, ≤5 × ULN for patients with liver involvement.
• Cardiac function (LVEF) ≥ 50% by echocardiography or MUGA.
• QTcF (Fridericia's) for male<450 ms, for female<470 ms at screening.
• Male and female of childbearing potential must agree to use contraceptive measures (such as IUD, contraceptive or condom) during the study and within 6 months after the end of the study.

Exclusion criteria

• Acute promyelocytic leukemia; or favorable cytogenetics, including t(8;21) or inv16 if known at the time of randomization.
• Except for CMMoL, patients with history of myeloproliferative neoplasms (MPN) (defined as a history of essential thrombocytosis or polycythemia vera, or idiopathic myelofibrosis prior to the diagnosis of AML) or combined MDS/MPN are not eligible.
• History of other malignancy within 3 years before randomization, expect for cancers that have been cured (basal cell or squamous cell carcinoma, superficial bladder cancer, carcinoma in situ of cervix and breast or prostate cancer with Gleason score of 6).
• Patients with clinical evidence of active CNS leukemia.
• Prior treatment for AML (except for hydroxyurea) or stem-cell transplantation.
• Administration of any therapy for MDS (conventional or investigational) within 2 weeks prior to of the first dose of study drug; use of hydroxyurea for the purpose of inhibiting rapid tumor proliferation within 24 hours before the first dose. Toxicities associated with prior MDS therapy have not recovered to grade 1 or less prior to start of treatment.
• Any major surgery or radiation therapy within 4 weeks.
• Patients with previous cumulative exposure to anthracyclines >368 mg/m^2 daunorubicin (or equivalent drug equivalent dose level).
• Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent obtaining informed consent.
• Patients with myocardial impairment of any cause (e.g. cardiomyopathy, ischemic heart disease, significant valvular dysfunction, hypertensive heart disease, and congestive heart failure) resulting in heart failure by NYHA Criteria (Class Ш or Ⅳ staging).
• Active or uncontrolled infection.
• Current evidence of invasive fungal infection (blood or tissue culture).
• Patients with known HIV, hepatitis B or hepatitis C infection.
• Patients who are hypersensitive to cytarabine, daunorubicin or liposomal products.
• Patients with a history of Wilson's disease or other copper-metabolism disorders.
• Participation in another clinical trial or treatment with any investigational drug within 28 days prior to screening.
• Any patients whom the investigator believes will not be a good candidate for the study.