CPX-351 Plus Enasidenib for Relapsed Acute Myelogenous Leukemia Characterized by the IDH2 Mutation
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 2
- 试验地点
- 3
- 主要终点
- Complete remission (CR)/CR with incomplete hematologic recovery (CRi) after induction therapy
研究概览
简要总结
This trial evaluates how well CPX-351 and enasidenib work in treating patients with acute myeloid leukemia characterized by IHD2 mutation. Drugs used in chemotherapy, such as 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. Enasidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving CPX-351 and enasidenib may work better in treating patients with acute myeloid leukemia, compared to giving only one of these therapies alone.
详细描述
PRIMARY OBJECTIVE:
I. To estimate the remission rate (defined as complete remission [CR]/ CR with incomplete hematologic recovery [CRi]) of the combination of liposome-encapsulated daunorubicin-cytarabine (CPX-351) plus enasidenib mesylate (enasidenib) in adults with relapsed acute myeloid leukemia (AML) characterized by a 2-hydroxyglutarate (2-HG) producing IDH2 mutations that include IDH2^R172 and IDH2^R140.
SECONDARY OBJECTIVES:
I. To evaluate persistent severe hematologic toxicity at induction day 60 in patients with a morphologic leukemia-free state (bone marrow blasts < 5%).
II. To evaluate delayed CR/CRi with enasidenib maintenance in participants with stable disease after induction with CPX-351.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Bone marrow blasts >= 5% that develops after CR/CRi in patient with prior history of AML, no restriction on prior number of relapses or regimens
- •AML characterized by the IDH2 gene mutation, without requirement for a particular allelic frequency
- •Patients previously treated with IDH2 inhibitor can be enrolled
- •At least a 3-month duration of CR/CRi prior to relapse
- •Relapses after allogeneic HSCT are included with a minimum of 3 from the date of allogeneic HSCT
- •Up to 1 cycle of hypomethylating agent monotherapy at time of relapse is allowed, must be discontinued at least 14 days prior to start of salvage induction
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Serum total bilirubin < 2.0 mg/dL, unless considered due to Gilbert's disease or leukemic involvement
- •Aspartate aminotransferase (AST), alanine aminotransferase (ALT) < 3 times the upper limit of normal, unless considered due to leukemic involvement
- •Alkaline phosphatase < 3 times the upper limit of normal, unless considered due to leukemic involvement
- •Serum creatinine =< 2.0 mg/dL, or creatinine clearance > 40 mL/min based on Cockcroft-Gault glomerular filtration rate (GFR)
- •Females of reproductive potential as well as fertile men and their partners who are female of reproductive potential must agree to abstain from sexual intercourse or to use two highly effective forms of contraception from the time of giving informed consent, during the study, and for four months (females and males) following the last dose of IDH inhibitor. A highly effective form of contraception is defined as hormonal oral contraceptives, injectables, patches, intrauterine devices, double-barrier method (eg, synthetic condoms, diaphragm or cervical cap with spermicidal foam, cream, or gel) or male partner sterilization
排除标准
- •Concurrent FLT3 mutation that the treating physician deems necessary to treat with FLT3-targeted therapy; whereas, patients with FLT3-mutated AML not treated with FLT3-targeted therapy can be enrolled
- •Acute promyelocytic leukemia
- •Inability to swallow medications or history of gastrointestinal (GI) malabsorptive disease
- •Active malignancy that would limit survival by less than two years
- •New York Heart Association class III or VI
- •Left ventricular ejection fraction < 40%
- •History of coronary stent placement that require mandatory continuation of dual-antiplatelet therapy
- •Baseline QT corrected interval based on Fridericia's formula (QTcF) interval > 450 ms
- •History of Wilson's disease or other copper handling disorders
- •Hypersensitivity to cytarabine, daunorubicin, or liposomal products
- •Active invasive fungal infection
- •Active bacterial or viral infection manifesting as fevers or hemodynamic instability within the past 72 hours
- •Lifetime cumulative daunorubicin-equivalent anthracycline dose > 368 mg/m^2
- •Pregnant or breast feeding
研究组 & 干预措施
Treatment (CPX-351, enasidenib mesylate)
See detailed description
干预措施: Enasidenib Mesylate (Drug)
Treatment (CPX-351, enasidenib mesylate)
See detailed description
干预措施: Liposome-encapsulated Daunorubicin-Cytarabine (Drug)
结局指标
主要结局
Complete remission (CR)/CR with incomplete hematologic recovery (CRi) after induction therapy
时间窗: Up to day 60
次要结局
- Overall survival(From day 1 of induction therapy, assessed at day 30 and 60)
- Proportion of patients who go on to receive allogeneic hematopoietic stem cell transplantation (HSCT) after achieving CR/CRi(Up to 2 years)
- Proportion of patients with persistent grade 4 hematologic toxicity per Common Terminology Criteria for Adverse Events (CTCAE) version 4.03(At day 60)
- Proportion of patients who achieve CR/CRi during maintenance therapy(Up to 2 years)
- Proportion of patients who achieve CR/complete remission with partial hematologic recovery (CRp) after induction therapy(Up to 2 years)
- Time to return of normal hematopoiesis(From day 1 of induction assessed up to 2 years)