A Phase IA/II, Two-arm, Multi-center, Open-label, Dose-escalation Study of LBH589 Administered Orally Via Different Dosing Schedules in Adult Patients With Advanced Hematological Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 175
- 试验地点
- 4
- 主要终点
- Number of Participants DLT in Arm 1 in Dose Escalation Phase
研究概览
简要总结
This study evaluated safety, tolerability, pharmacokinetics and preliminary anti-leukemic or anti-tumor activity of LBH589B in adult patients with advanced hematological malignancies
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
Arm 1, Group X
干预措施: LBH589 (Drug)
Arm 1, Group Y
干预措施: LBH589 (Drug)
Arm 2, Group X
干预措施: LBH589 (Drug)
Arm 2, Group Y
Panobinostat was administered orally, once-a-day, on Monday-Wednesday-Friday (MWF), every other week, as part of a 28-day treatment cycle. Group Y is a sub-arm, based on disease indication.
干预措施: LBH589 (Drug)
结局指标
主要结局
Number of Participants DLT in Arm 1 in Dose Escalation Phase
时间窗: Cycle 1 (28-day treatment cycle)
Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) for consecutive dosing schedule (MWF weekly). A 3-parameter version of a Bayesian logistic regression model with overdose control (Babb, Rogatko, and Zacks 1998) was used during the dose escalation phase for dose level selection and determination of the MTD.
Number of Participants DLT in Arm 2 in Dose Escalation Phase
时间窗: Cycle 1 (28-day treamtent cycle)
Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) for intermittent dosing schedule (MWF weekly). A 3-parameter version of a Bayesian logistic regression model with overdose control (Babb, Rogatko, and Zacks 1998) was used during the dose escalation phase for dose level selection and determination of the MTD.
次要结局
- Half Life of Panobinostat After Multiple Doses in Arm 1 on Day 15(Day 15)
- Geometric Mean Ratio (GMR) Comparing Treatment Days in Arm 1(Day 15/day 1)
- Response as Per Investigator Assessment for Patients With Acute Myelogenous Leukemia (AML) in Expansion Phase(1.2 years)
- Response as Per Investigator Assessment for Patients With Myelodysplastic Syndromes (MDS)(3.5 years)
- Maximum Plasma Concentration of Panobinostat After the First Dose in Arms 1 and 2(Day 1)
- Maximum Plasma Concentration of Panobinostat After Multiple Doses in Arm 1 on Day 15(Day 15)
- Percentages of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 1 (MWF Every Week), Group X(Days 1, 5, 8, 10, 15)
- Response as Per Investigator Assessment for Patients With Acute Myelogenous Leukemia (AML)(3.5 years)
- Response as Per Investigator Assessment for Patients With Hodgkin's Lymphoma (HD)(3.5 years)
- Percentages of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 2 (MWF Every Other Week), Group X(Days 5, 8, 10, 12, 15, End of study, Unscheduled (up to 3.5 years))
- Percentage of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 2 (MWF Every Other Week), Group Y(Days 5, 8, 10, 12, 15, End of study (up to 3.5 years))
- Highest Percent Change in Fetal Hemoglobin From Baseline in Arm 1 (MWF Every Week)(Post dose to pre-dose (up to 3.5 years))
- Highest Percent Change of Fetal Hemoglobin From Baseline in Arm 2 (MWF Every Other Week)(Post dose to pre-dose (up to 3.5 years))
- Half Life of Panobinostat After the First Dose in Arms 1 and 2(Day 1)
- Percentages of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 1 (MWF Every Week), Group Y(Days 5, 8, end of study (up to 3.5 years))