Phase II Study of CPX-351 (Cytarabine:Daunorubicin) Liposome Injection in Patients With Newly Diagnosed AML at High Risk for Induction Mortality
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Number of Participants With a Response
研究概览
简要总结
This phase II trial studies the best dose and how well liposomal cytarabine-daunorubicin CPX-351 (CPX-351) works in treating patients with newly diagnosed acute myeloid leukemia and who are at risk for not responding well to treatment. Liposomal cytarabine-daunorubicin CPX-351 combines two chemotherapy drugs that are known to help each other work better, and may work to stop the growth of cancer cells by blocking the cells from dividing.
详细描述
PRIMARY OBJECTIVE:
I. To assess preliminary efficacy (as determined by the rate of complete response [CR] or CR with incomplete blood count recovery [CRi]) of two or three dose levels of CPX-351 in patients with newly diagnosed acute myeloid leukemia (AML) at high risk for induction mortality, defined as 30-50% predicted risk of death by day 60, and to select the most promising dose level for further efficacy testing.
SECONDARY OBJECTIVE:
I. To confirm the rate of dose limiting toxicities, including induction mortality (at day 60) for two different sub-maximum tolerated dose (MTD) dose levels (50 and 75 U/m^2).
EXPLORATORY OBJECTIVES:
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ability to understand and voluntarily sign an informed consent form
- •Pathological diagnosis of AML according to World Health Organization (WHO) criteria (with at least 20% blasts in the peripheral blood or bone marrow): newly diagnosed de novo AML; except for acute promyelocytic leukemia (APL); newly diagnosed secondary AML, defined as having a history of an antecedent hematologic disorder (myelodysplastic syndromes [MDS], myeloproliferative disease [MPD] or history of cytotoxic treatment for non-hematologic malignancy) or apparent de novo AML with MDS-associated karyotype
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-3
- •Serum creatinine =< 2.0 mg/dL
- •Serum total bilirubin =< 2.0 mg/dL
- •Serum alanine aminotransferase < 3 times the upper limit of normal (ULN); Note: If elevated liver enzymes are related to disease alanine aminotransferase (ALT) should be < 5 times ULN
- •To be considered at high risk for induction mortality patients must have 1 or 2 of the following risk factors (patients >= 60 must have at least 1 risk factor, patients < 60 must have at least 2 risk factors) present; at least one risk factor in every patient must be an AML-related factor:
- •AML-related factors include:
- •Antecedent hematologic disorder (AHD) (MDS, chronic myelomonocytic leukemia [CMML], or MPD) or history of exposure to cytotoxic chemotherapy [therapy-related (t)-AML]), or WHO-defined AML with MDS-related changes or apparent de novo AML with MDS-associated karyotype
- •Unfavorable cytogenetics as defined by the European Leukemia Net
- •Patient-related factors:
- •Age >= 70
- •ECOG performance status (PS) >= 2
- •Co-morbidities:
- •Serum creatinine > 1.3 g/dL
- •Cardiac ejection fraction >= 50% by echocardiography or multi gated acquisition (MUGA) (when left ventricular ejection fraction [LVEF] expressed as a range, at least the upper limit should include 50%)
- •Able to adhere to the study visit schedule and other protocol requirements
- •All men and women must agree to practice effective contraception during the study period if not otherwise documented to be infertile
排除标准
- •Patients with history of second malignancy are eligible if they have documentation of disease stability, off therapy, based on computed tomography (CT) scan or other measures for the 6 months prior to entry in core
- •Any serious medical condition or psychiatric illness that would prevent the patient from providing informed consent
- •Chemotherapy or other investigational anticancer therapeutic drugs in the two weeks prior to study entry; in the event of rapidly proliferative disease, however, the use of hydroxyurea is permitted up to 24 hours before study entry in core
- •Evidence of active central nervous system (CNS) leukemia
- •Pregnant or lactating women
- •Uncontrolled infection; to be eligible, patients receiving treatment for an infection (antibiotic, antifungal or antiviral treatment) must be afebrile (< 38.3 degrees Celsius [C]) and without hemodynamic instability or dyspnea from pneumonia for > 48 hours (hrs) prior to the start of induction therapy
- •Hypersensitivity to cytarabine, daunorubicin or liposomal products
- •History of Wilson's disease or other copper-metabolism disorder
研究组 & 干预措施
Arm II (intermediate-dose (75 units/m^2) CPX-351)
Patients receive intermediate-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients with persistent disease may receive a second course with treatment on days 1 and 3.
干预措施: Liposome-encapsulated Daunorubicin-Cytarabine (Drug)
Arm III (standard-dose (100 units/m^2) CPX-351)
Patients receive standard-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients with persistent disease may receive a second course with treatment on days 1 and 3.
干预措施: Laboratory Biomarker Analysis (Other)
Arm III (standard-dose (100 units/m^2) CPX-351)
Patients receive standard-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients with persistent disease may receive a second course with treatment on days 1 and 3.
干预措施: Liposome-encapsulated Daunorubicin-Cytarabine (Drug)
Arm I (lower-dose (50 units/m^2) CPX-351)
Patients receive lower-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5 of a 28-day course. Patients with persistent disease may receive a second course with treatment on days 1 and 3.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (lower-dose (50 units/m^2) CPX-351)
Patients receive lower-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5 of a 28-day course. Patients with persistent disease may receive a second course with treatment on days 1 and 3.
干预措施: Liposome-encapsulated Daunorubicin-Cytarabine (Drug)
Arm II (intermediate-dose (75 units/m^2) CPX-351)
Patients receive intermediate-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients with persistent disease may receive a second course with treatment on days 1 and 3.
干预措施: Laboratory Biomarker Analysis (Other)
结局指标
主要结局
Number of Participants With a Response
时间窗: Up to 8 weeks (after induction therapy)
Response is defined as Complete response (CR) or CR with incomplete blood count recovery (CRi) rate: Complete Remission (CR) is Bone marrow blasts \<5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count \>1.0 x 10\^9/L (1000/μL); platelet count \>100 x 10\^9/L (100,000/μL). Complete Response with incomplete blood count recovery (CRi) is All CR criteria except for residual neutropenia (\<1.0 x 10\^9/L \[1000/μL\]) and/or thrombocytopenia (\<100 x 10\^9/L \[100,000/μL\]).
次要结局
- Number of Participants Who Experienced Dose-limiting Toxicity (DLT)(Up to day 60)