An Open Label Phase I Trial of Intravenous Volasertib in Combination With Subcutaneous Azacitidine in Japanese Patients With Higher-risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)
研究概览
简要总结
To identify the maximum tolerated dose or recommended dose for further development of volasertib in combination with azacitidine in Japanese patients with myelodysplastic syndromes or chronic myelomonocytic leukemia, and evaluate the safety and tolerability, pharmacokinetics and the preliminary efficacy of this combination.
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
- 20 Years 至 80 Years（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
A
Volasertib escalating doses + azacitidine
干预措施: Azacitidine (Drug)
A
Volasertib escalating doses + azacitidine
干预措施: Volasertib (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)
时间窗: Up to 57 days.
This outcome measure presents number of participants with DLTs in the first cycle for the determination of MTD. DLT was defined as any of the following Adverse Events (AEs) considered to be related to the study drug (Volasertib and/or Azacitidine). 1. Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3 drug-related non-haematologic toxicity. 2. Drug-related AEs that led to inability to deliver the full dose of the study drugs (Volasertib and/or Azacitidine) according to the assigned dose level within Cycle 1. 3. Absence of haematological recovery (sustained CTCAE grade ≥3 thrombocytopenia \<50000/mm\^3 and/or neutropenia \<1000/mm\^3) after completing Cycle 1 and lasting at least until Day 57 (from Day 1 of Cycle 1) despite complete marrow blast clearance on Day 29 (\<5% blasts in the bone marrow. 4. Any other drug-related AEs that required treatment delay of ≥4 weeks between the Cycle 1 and Cycle 2 (i.e., Cycle 2 was not started until Day 57 of Cycle 1)).
Maximum Tolerated Dose of Volasertib
时间窗: Up to 57 days.
This outcome measure presents MTD of Volasertib in Combination with Azacitidine. The MTD was defined as the highest dose level at which Dose Limiting Toxicities (DLTs) were reported in not more than 1 in 6 evaluable patients during Cycle 1.
次要结局
- Overall Objective Response (OR): Complete Remission (CR), Partial Remission (PR), or Marrow CR (mCR)(Up to 9 months.)
- Maximum Measured Concentration of the Volasertib 200 mg in Plasma (Cmax)(-0.05 hours before drug administration and 0:30 (hours:minutes), 1:00, 1:30, 2:00, 3:00, 4:00, 24:30, 48:30, 96:30, 144:30 and 335:55 after drug administration.)
- Area Under the Concentration-Time Curve of Volasertib 200 mg in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)(-0.05 hours before drug administration and 0:30 (hours:minutes), 1:00, 1:30, 2:00, 3:00, 4:00, 24:30, 48:30, 96:30, 144:30 and 335:55 after drug administration.)