A Randomized, Open-label, Two-period, Two-way Crossover Bioequivalence Study of Two (Cytarabine: Daunorubicin) Liposome for Injection in Elderly AML Subjects
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Maximum (peak) plasma drug concentration (Cmax) of daunorubicin cytarabine liposomes
研究概览
简要总结
The purpose of this study is to determine the bioequivalence of (cytarabine: daunorubicin) liposome for injection and Vyxeos in elderly acute myeloid leukemia (AML) subjects.
详细描述
This is a multi-center, randomized, open-label, two-period, two-sequence, two-way crossover bioequivalence study of (cytarabine: daunorubicin) liposome for injection manufactured by CSPC Zhongnuo Pharmaceutical Technology Co., Ltd compared with Vyxeos manufactured by Jazz Pharmaceuticals, Inc. in elderly AML subjects. Patients who have achieved CR/CRi after induction treatment will be randomized to sequence A (T-R): (cytarabine: daunorubicin) liposome on C1D1 and C1D3/ Vyxeos on C2D1 and C2D3 or sequence B(R-T): Vyxeos on C1D1 and C1D3/ (cytarabine: daunorubicin) liposome on C2D1 and C2D3. Randomization will be in a 1:1 ratio. Forty to sixty subjects will be enrolled to ensure 36 evaluable subjects.
Serial blood samples for determination of liposomal encapsulated cytarabine and liposomal encapsulated daunorubicin plasma concentration for PK analysis will be obtained in each cycle.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 55 Years 至 75 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.
- •Male or female between 55-75 years of age (inclusive).
- •Subjects 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 or who have achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi) after preceding induction therapy.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Adequate hematopoietic, renal and liver function.
- •Cardiac function (LVEF) ≥ 50% and QTcF (Fridericia's) for male<450 ms, for female<470 ms at screening.
- •Women of childbearing potential should agree to use contraceptive measures (such as IUD, contraceptive or condom) during the study and within 6 months after the end of the study.
排除标准
- •Subjects who are diagnosed as acute promyelocytic leukemia.
- •Subjects with clinical evidence of active CNS leukemia.
- •Subjects with any other active malignancy expect for those have been cured (basal cell carcinoma, superficial bladder cancer, cervical cancer in situ, carcinoma in situ of breast or prostate cancer with Gleason score <6).
- •For subjects with induction remission who go directly to randomisation, their antitumour drug elution is required prior to the first dose in the consolidation phase for a minimum of 5 half-lives or 4 weeks, whichever is shorter.
- •Subjects with a history of any major surgery or radiation therapy within 4 weeks prior to the first dose.
- •Subjects with active cardiovascular disease within 6 months prior to the first dose.
- •Subjects with severe hemorrhagic disorders or diseases may cause spontaneous bleeding.
- •Subjects with active or history of cerebrovascular disease, such as stroke, cerebral hemorrhage within 6 months prior to the first dose.
- •Subjects with severe pulmonary disease within 2 weeks prior to the first dose.
- •Subjects with active or uncontrolled infection.
- •Subjects with previous cumulative exposure to anthracyclines >302 mg/m^2 daunorubicin (or equivalent drug equivalent dose level).
- •Subjects with hypersensitivity to liposomal products.
- •Subjects with a history of Wilson's disease or other copper-metabolism disorder.
- •Subjects with known HIV, hepatitis B or hepatitis C infection.
- •Participation in another clinical trial or treatment with any investigational drug within 28 days of study start
- •Female subjects who are pregnant, breast-feeding, or who are likely to become pregnant during the study.
- •Any subject whom the Investigator believes will not be a good candidate for the study.
研究组 & 干预措施
Sequence A (T-R)
(cytarabine: daunorubicin) liposome for injection followed by Vyxeos
干预措施: Vyxeos (Drug)
Sequence B (R-T)
Vyxeos followed by (cytarabine: daunorubicin) liposome for injection
干预措施: Vyxeos (Drug)
结局指标
主要结局
Maximum (peak) plasma drug concentration (Cmax) of daunorubicin cytarabine liposomes
时间窗: 30 minutes before administration and 1.5, 2, 5,9,24,48,72,120,168hours after administration of Day 1.
Maximum (peak) plasma drug concentration is a Pharmacokinetic parameter
Area under the plasma concentration versus time curve calculated from 0 to 48h post administration (AUC0-48h) of daunorubicin cytarabine liposomes
时间窗: 30 minutes before administration and 1.5, 2, 5,9,24,48,72,120,168hours after administration of Day 1
Area under the plasma concentration-time curve from time zero to time 48 hours is a Pharmacokinetic parameter
次要结局
- Incidence of treatment-emergent adverse events (TEAEs)(Up to 35 calendar days after the last administration of the investigational product.)
- Relapse-free survival(Up to 3 years.)
- Proportion of subjects who achieve complete remission with MRD negativity(Up to 1 year.)
- Maximum (peak) plasma drug concentration (Cmax) of free daunorubicin and cytarabine(30 minutes before administration and 1.5, 2, 5,9,24,48,72,120,168hours after administration of Day 1.)
- Area under the plasma concentration versus time curve calculated from 0 to 48h post administration (AUC0-48h) of free daunorubicin and cytarabine(30 minutes before administration and 1.5, 2, 5,9,24,48,72,120,168hours after administration of Day 1.)
- Maximum (peak) plasma drug concentration (Cmax) of total daunorubicin and cytarabine(30 minutes before administration and 1.5, 2, 5,9,24,48,72,120,168hours after administration of Day 1.)
- Area under the plasma concentration versus time curve calculated from 0 to 48h post administration (AUC0-48h) of total daunorubicin and cytarabine(30 minutes before administration and 1.5, 2, 5,9,24,48,72,120,168hours after administration of Day 1.)
- Complete remission rate(Up to 1 year.)
- Composite remission rate(Up to 1 year.)