A Clinical Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Mitoxantrone Hydrochloride Liposome Injection Combined With Chemotherapy in Previously Untreated de Novo Acute Myeloid Leukemia
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Incidence of treatment-emergent adverse events (TEAEs)
研究概览
简要总结
The purpose of this study is to determine the safety, efficacy and pharmacokinetics of mitoxantrone hydrochloride liposome injection combined with chemotherapy in previously untreated de novo acute myeloid leukemia.
详细描述
This is a prospective, multi-center, randomized, open-label, three-arm clinical study to explore the efficacy among three chemotherapy regimens combined with mitoxantrone hydrochloride liposome in previously untreated de novo acute myeloid leukemia. Patients will be randomized to different treatment group and be given different induction therapy in the first cycle. If patients do not achieve Morphologic Leukemia-free State (MLFS) after the first induction cycle, they will receive the second induction therapy with mitoxantrone hydrochloride liposome, cytarabine and venetoclax. Mitoxantrone hydrochloride liposome will be given on day 1 at the dose of 24 mg/m2 or 30 mg/m2 and be combined with cytarabine, venetoclax or homoharringtonine. A maximum of 2 cycles of induction therapy are planned.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to understand the study and voluntarily sign informed consent.
- •Age: 18~65 (including 18) years old, gender unlimited.
- •Patients diagnosed with acute myeloid leukemia according to "The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia" who haven't been treated.
- •Eastern Cooperative Oncology Group (ECOG) physical state score: 0-
- •Fit for intensive chemotherapy.
- •The function of main organs should meet the following standards before treatment:
- •Kidney: Serum creatinine ≤ 1.5 × Upper limit of normal range (ULN) Liver: Total bilirubin ≤ 1.5 × ULN, AST and ALT ≤ 3× ULN
- •Patients should agree to use contraception (such as intrauterine device [IUD], contraceptive pill or condom) during the study period and within 6 months after the end of the study; Female patients must have a negative serum pregnancy test within 7 days before enrollment.
排除标准
- •Any of the following cases:(1) diagnosed as acute promyelocytic leukemia (APL);(2) chronic myelogenous leukemia in blast crisis;(3) AML with central nervous system leukemia.
- •AML arising from prior cytotoxic chemotherapy or radiotherapy for other tumours.
- •Patient has been previously diagnosed with another malignancy in last 5 years (except for cured basal cell carcinoma of skin or cervical carcinoma in situ).
- •Has been previously treated with doxorubicin or other anthracyclines and drugs for AML.
- •Allergic history of mitoxantrone hydrochloride injection or any other drugs used in this study.
- •Those on systemic anti-infective therapy with poorly controlled infection (signs of infection progression within 1 week prior to the first dose, or as determined by the investigator).
- •Patient who is suffering from severe hemorrhagic diseases, such as haemophilia A, haemophilia B, von Willebrand disease and any other spontaneous bleeding require medical treatment.
- •The estimated survival time is less than 3 months.
- •Any of the following conditions occurs in cardiac function:(1) Long QTc syndrome or QTc interval > 480 ms;(2) Complete left bundle branch block or severe atrioventricular block disease (without a pacemaker);(3) Serious and uncontrolled arrhythmias and unstable angina pectoris requiring drug treatment;(4) History of chronic congestive heart failure, New York Heart Association (NYHA)≥grade 3;(5) The cardiac ejection fraction is less than 50% in Echocardiography;(6)Uncontrollable hypertension (defined as multiple measurements of systolic blood pressure > 150 mmHg or diastolic blood pressure > 90 mmHg under drug control);(7) History of myocardial infarction, unstable angina pectoris, viral myocarditis or severe pericardial disease, ECG evidence of acute ischemia or active conduction system abnormalities within 6 months before first dose.
- •Patients have thromboembolic events within 6 months prior to first dose, such as cerebrovascular accidents (including transient ischemic attack) and pulmonary embolism.
- •HBsAg/HBcAb positive with HBV-DNA higher than the lower limit of the detection value of the research center , hepatitis C antibody-positive with HCV-RNA higher than the lower limit of the detection value of the research center, or HIV antibody positive in the preliminary screening.
- •Patients who have been treated with strong/moderate CYP3A inducers/inhibitors or P-gp inhibitors within 7 days prior to first dose (for treatment group 3 only).
- •Patients who cannot take oral medications or have absorption disorder (for treatment group 3 only).
- •Patient is suffering from any serious and /or non-controllable disease, or the investigator determines that the disease might affect the participation of patients in the study, including (but not limited to, uncontrolled diabetes, dialysis related kidney diseases, severe liver diseases, life-threatening autoimmune diseases and hemorrhagic diseases, drug abuse, neurological diseases, etc.).
- •Pregnant or lactating female.
- •Patients who are not suitable for this study as decided by the investigator due to other reasons.
研究组 & 干预措施
mitoxantrone hydrochloride liposome injection combined with of cytarabine
Patients will receive mitoxantrone hydrochloride liposome injection combined with standard-dose of cytarabine.
干预措施: Mitoxantrone hydrochloride liposome injection30mg/m2 (Drug)
mitoxantrone hydrochloride liposome with cytarabine and homoharringtonine
Patients will receive mitoxantrone hydrochloride liposome injection combined with intermediate-dose of cytarabine and homoharringtonine.
干预措施: HomoharringtonineD1-D7(2mg/m2/day) (Drug)
mitoxantrone hydrochloride liposome with cytarabine and homoharringtonine
Patients will receive mitoxantrone hydrochloride liposome injection combined with intermediate-dose of cytarabine and homoharringtonine.
干预措施: Mitoxantrone hydrochloride liposome injection24mg/m2 (Drug)
mitoxantrone hydrochloride liposome injection combined with cytarabine and venetoclax
Patients will receive mitoxantrone hydrochloride liposome injection with cytarabine and venetoclax.
干预措施: Mitoxantrone hydrochloride liposome injection30mg/m2 (Drug)
mitoxantrone hydrochloride liposome injection combined with cytarabine and venetoclax
Patients will receive mitoxantrone hydrochloride liposome injection with cytarabine and venetoclax.
干预措施: Venetoclax (d4 100mg/day, d5200mg/day ,d6-d12 400mg/day) (Drug)
结局指标
主要结局
Incidence of treatment-emergent adverse events (TEAEs)
时间窗: Up to approximately one month
The frequency and severity of adverse events during treatment, abnormalities in vital signs, physical examinations, laboratory tests, etc
次要结局
- Blood concentrations of total and free mitoxantrone.(30 minutes before administration and 5min, 6, 24, 72, 144, 288, 432, 648 hours after administration of Mitoxantrone hydrochloride liposome on day 1)
- Event-free survival (EFS)(Up to approximately 3 years.)
- Complete remission rate（CR）(Up to approximately nine weeks)
- Overall survival (OS)(Up to approximately 3 years.)
- Complete remission or complete remission with partial hematologic recovery (CR/CRh)(Up to approximately nine weeks)
- Composite remission rate (CRc)(Up to approximately nine weeks)
- Minimal Residual Disease (MRD)-negative composite remission rates(Up to approximately nine weeks)
- Relapse-free Survival (RFS)(Up to approximately 3 years.)