Liposomal Cytarabine and Daunorubicin (CPX-351) for Adults With Untreated High-Risk MDS and Non-APL AML at High Risk of Treatment-Related Mortality
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 2
- 主要终点
- Treatment-related Mortality Rate. (TRM)
研究概览
简要总结
This randomized clinical trial studies liposomal cytarabine-daunorubicin CPX-351 in treating patients with untreated myelodysplastic syndrome or acute myeloid leukemia. Drugs used in chemotherapy, such as liposomal cytarabine-daunorubicin CPX-351, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
详细描述
PRIMARY OBJECTIVES:
I. Estimate whether the 32 units/m^2 or the 64 units/m^2 or both dose levels of CPX-351 (liposomal cytarabine-daunorubicin CPX-351) are likely to improve treatment-related mortality (TRM) rate while keeping the complete remission (CR) rate constant in patients with untreated high-risk myelodysplastic syndrome (MDS) or non-acute promyelocytic leukemia (APL) acute myeloid leukemia (AML) at high risk of TRM.
SECONDARY OBJECTIVES:
I. Describe the CR/CR with incomplete platelet count recovery (CRp) rate after up to 4 cycles of induction/re-induction therapy.
II. Describe the event-free survival, disease-free survival, and overall survival of patients who achieve CR/CRp.
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
- •Diagnosis of untreated "high-risk" MDS (>= 10% blasts) or AML other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 2008 World Health Organization (WHO) classification; patients with biphenotypic AML are eligible; outside diagnostic material is acceptable as long as peripheral blood and/or bone marrow slides are reviewed at the study institution and cytogenetic/molecular information is available
- •Prior hydroxyurea for AML is permitted but should be discontinued prior to start of CPX-351 treatment
- •Azacitidine, decitabine, lenalidomide, and growth factors are permitted for low-risk MDS (< 10% blasts); all treatments for MDS should be discontinued prior to start of CPX-351 treatment
- •Treatment-related mortality (TRM) score >= 13.1 as calculated with simplified model
- •Bilirubin < 2.0 mg/mL x upper limit of normal; this requirement reflects the excretion of CPX-351 by the liver
- •Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 4.0 x upper limit of normal; this requirement reflects the excretion of CPX-351 by the liver
- •Left ventricular ejection fraction (LVEF) >= 40%, assessed within 28 days prior to registration, e.g. by multi gated acquisition (MUGA) scan or echocardiography, or other appropriate diagnostic modality
- •Patients with symptoms/signs of hyperleukocytosis or white blood cell (WBC) > 100,000/uL can be treated with leukapheresis prior to enrollment
- •Provide signed written informed consent
排除标准
- •Refractory/relapsing blast crisis of chronic myelogenous leukemia (CML)
- •Concomitant illness associated with a likely survival of < 1 year
- •Active systemic fungal, bacterial, viral, or other infection, unless under treatment with anti-microbials and controlled/stable, as defined as being afebrile and hemodynamically stable for 24-48 hours
研究组 & 干预措施
Arm I (lower-dose liposomal cytarabine-daunorubicin CPX-351)
INDUCTION/RE-INDUCTION: Patients receive lower-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or CRp continue on to consolidation.
CONSOLIDATION: Patients receive lower-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1 and 3. Treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (lower-dose liposomal cytarabine-daunorubicin CPX-351)
INDUCTION/RE-INDUCTION: Patients receive lower-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or CRp continue on to consolidation.
CONSOLIDATION: Patients receive lower-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1 and 3. Treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Liposomal Cytarabine-Daunorubicin CPX-351 (Drug)
Arm II (closed to accrual effective 4/21/14)
INDUCTION/RE-INDUCTION: Patients receive higher-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or CRp continue on to consolidation.
CONSOLIDATION: Patients receive higher-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1 and 3. Treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (closed to accrual effective 4/21/14)
INDUCTION/RE-INDUCTION: Patients receive higher-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or CRp continue on to consolidation.
CONSOLIDATION: Patients receive higher-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1 and 3. Treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Liposomal Cytarabine-Daunorubicin CPX-351 (Drug)
结局指标
主要结局
Treatment-related Mortality Rate. (TRM)
时间窗: Up to 1 month after completion of study treatment
Estimate whether the 32 units/m2 or the 64 units/m2 or both dose levels of CPX-351 are likely to improve treatment-related mortality (TRM) rate while keeping the CR rate constant in patients with untreated high-risk MDS or non-APL AML at high risk of TRM.
次要结局
- Overall Remission Rate (CR+CRp)(Up to day 28)
研究者
Roland Walter
Principal Investigator
Fred Hutchinson Cancer Center