Epacadostat With Cladribine and Cytarabine (ECC) in Relapsed / Refractory AML Patients Fit for Intensive Chemotherapy; a Phase I Study.
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Dose finding
研究概览
简要总结
This trial assess the maximum tolerated dose (MTD) and to characterize dose-limiting toxicities (DLTs) of epacadostat when added to the cladribine/cytarabine chemotherapy in relapsed / refractory AML patients fit for intensive treatment
详细描述
Background and Rationale:
Epacadostat (INCB024360) is an Inhibitor of Indoleamine 2,3- dioxygenase 1 (IDO1). Indoleamine 2,3- dioxygenase 1 (IDO1) is a 403 amino acid cytosolic haem enzyme encoded by the INDO gene on human chromosome 8p22. IDO1 is responsible for the catabolism of the essential amino acid tryptophan (trp) to kynurenine (kyn) within immune cells and a subset of tumor cells resulting in inhibition of antitumor cell-mediated immune responses. Increased IDO activity correlates with lower CR rates and shorter OS in AML.
Objective:
The primary objective is to determine the maximum tolerated dose (MTD) and to characterize dose-limiting toxicities (DLTs) of epacadostat when added to the cladribine/cytarabine chemotherapy in relapsed / refractory AML patients fit for intensive treatment
Study Duration:
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
- •Relapsed/refractory AML (according to the 2016 World Health Organization (WHO) classification definition of ≥ 20% blasts; Arber et al, 2016) after at least one line of treatment and suitable for intensive treatment (including stem cell transplantation) without severe concurrent infections.
- •Patients must be aged > 18 years, and must have given voluntary written informed consent.
- •Women of childbearing potential having a negative serum pregnancy test at screening or at least within 48 hours before start with epacadostat, and willing to use an effective contraceptive method (intrauterine devices, hormonal contraceptives, contraceptive pill, implants, transdermal patches, hormonal vaginal devices, infusions with prolonged release) during the study and for at least 6 months after the last study drug administration
- •Men willing to use an effective contraceptive method (eg, condom, vasectomy) during the study and for at least 6 months after the last study drug administration.
排除标准
- •Prior or concurrent malignancy, except for the following: adequately treated basal cell or squamous cell skin cancer, or any other cancer from which the subject has been disease-free for more than 6 months.
- •APL (acute promyelocytic leukemia) or AML type M3, are excluded from the trial
- •Treatment with any investigational product within 4 weeks before the first administration of epacadostat (INCB024360)
- •Abnormal organ function if not caused by the underlying disease as considered by the treating physician
- •Use of immune-suppressive agents for the past 4 weeks before the first administration of epacadostat (INCB024360). For regular use of systemic corticosteroids, subjects may only be included after stepwise discontinuation to be free of steroids for a minimum of 5 days before the first administration of epacadostat (INCB024360)
研究组 & 干预措施
Dosis finding
Epacadostat is given for 2 cycles of 28 days at a dose according to the titration design together with standard chemotherapy (Cladribine and Cytarabine)
干预措施: Cladribine (Drug)
Dosis finding
Epacadostat is given for 2 cycles of 28 days at a dose according to the titration design together with standard chemotherapy (Cladribine and Cytarabine)
干预措施: Epacadostat (Drug)
Dosis finding
Epacadostat is given for 2 cycles of 28 days at a dose according to the titration design together with standard chemotherapy (Cladribine and Cytarabine)
干预措施: Cytarabine (Drug)
结局指标
主要结局
Dose finding
时间窗: 30 days
To determine the maximum tolerated dose (MTD) and to characterize dose-limiting toxicities (DLTs) of epacadostat
次要结局
- Rate of morphologic complete remission (CR)(60 days)
- Adverse events(100 days)
- Overall survival(12 months)