A Phase I Study of the Safety, Pharmacokinetics and Pharmacodynamics of Escalating Doses of the Selective Inhibitor of Nuclear Export/SINE™ Compound KPT-330 in Patients With Advanced Hematological Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 286
- 试验地点
- 12
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
研究概览
简要总结
The purpose of this research study is to find out more information relating to the highest dose of KCP-330 that can be given safely and side effects it may cause, to examine how the body affects KCP-330 concentrations in the blood (pharmacokinetics or PK), to examine the effects of KCP-330 on the body (pharmacodynamics or PDn) and to obtain information on its effectiveness in treating cancer.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
selinexor
干预措施: KPT-330 (Drug)
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
时间窗: From first dose of study drug administration to end of treatment (up to 27 months)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product during the course of a study and which does not necessarily have to have a causal relationship with this treatment. An Serious adverse event (SAE) was an AE resulting in any of the following outcomes: death; life-threatening event; required or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. TEAEs are any untoward medical incidence in a participant during administered study treatment, whether or not these events were related to study treatment.
Recommended Phase 2 Dose (RP2D) of Selinexor
时间窗: From first dose of study drug administration to end of treatment (up to 27 months)
Recommended Phase 2 dose was determined by maximum tolerated dose (MTD). MTD was defined as the next lower dose level below the one in which \> 1 of 3 participants or ≥ 2 of 6 participants experienced dose-limiting toxicity (DLT), provided that that dose level is ≤25% lower than the highest dose tested. If the projected MTD was \>25% lower than the highest dose tested, then an additional cohort of ≥3 participants were added at a dose that was intermediate between the intolerable dose and the next lower dose.
次要结局
- Maximum Observed Plasma Concentration (Cmax) of Selinexor(0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2)
- Average Concentration From Time 0 to 24 Hours (Cavg0-24h) of Selinexor(0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2)
- Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selinexor(0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2)
- Time to Maximum Observed Concentration (Tmax) of Selinexor(0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2)
- Area Under the Concentration-Time Curve From Time 0 to t (AUC0-t) of Selinexor(0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2)
- Apparent Volume of Distribution Uncorrected for Fraction Absorbed (Vd/F) of Selinexor(0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2)
- Apparent Total Body Clearance, Uncorrected for Fraction Absorbed (Cl/F) of Selinexor(0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2)
- Terminal Half-Life (t½) of Selinexor(0 (pre-dose), 0.5, 1, 2, 4, 8, 24 and 48 hours post-dose on Day 1, 8 of Cycle 1 and Days 15, 16 or 17 of Cycle 2)
- Number of Participants With Overall Response of Selinexor(From first dose of study drug administration to end of treatment (up to 27 months))
- Duration of Response(From first dose of study drug administration to end of treatment (up to 27 months))
- Progression-free Survival(Cycle 1 Day 1 to End of Treatment (up to 27 months))
- Duration of at Least Stable Disease(Cycle 1 Day 1 to End of Treatment (up to 27 months))
- Overall Survival(Cycle 1 Day 1 to End of Treatment (up to 27 months))