Phase 1b Study of Venetoclax and Dinaciclib (MK7965) in Patients With Relapsed/Refractory Acute Myeloid Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 48
- 试验地点
- 13
- 主要终点
- Tmax of Venetoclax
研究概览
简要总结
An open-label, dose-escalation study to assess safety, pharmacokinetics and efficacy as well as determine the recommended Phase 2 doses of co-administered therapy of dinaciclib and venetoclax for patients with relapsed or refractory Acute Myeloid Leukemia (R/R AML).
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
- •Diagnosis of acute myeloid leukemia (AML) by World Health Organization criteria excluding acute promyelocytic leukemia (APL)-M
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Participant must have adequate hematologic, renal, and liver function laboratory values as described in the protocol.
排除标准
- •Known central nervous system leukemia
- •Severe chronic obstructive pulmonary disease (COPD) with hypoxemia
- •History of any malignancy within the last 6 months except for those specified in this protocol and low-grade malignancies not requiring active treatment.
- •Prior allogeneic stem cell transplant within 6 months of study drug administration and no requirement for graft versus host therapy.
- •History of clinically significant medical condition that, in the opinion of the investigator, would adversely affect participation in this study.
- •Known active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
- •History of tumor lysis syndrome (TLS) due to previous exposure to venetoclax.
研究组 & 干预措施
Venetoclax + Dinaciclib
Venetoclax and dinaciclib will be administered in combination. Different combinations of dose levels for venetoclax and dinaciclib will be explored.
干预措施: Venetoclax (Drug)
Venetoclax + Dinaciclib
Venetoclax and dinaciclib will be administered in combination. Different combinations of dose levels for venetoclax and dinaciclib will be explored.
干预措施: Dinaciclib (Drug)
结局指标
主要结局
Tmax of Venetoclax
时间窗: Approximately 29 days after first dose of study drug
Time to maximum plasma concentration (Tmax) of venetoclax.
Recommended Phase 2 Dose (RPTD) of co-administered Dinaciclib and Venetoclax
时间窗: Minimum first cycle of dosing (21 days)
Tthe RPTD of co-administered venetoclax and dinaciclib will be determined during the dose escalation phase of the study. RPTD will be determined using available safety and pharmacokinetics data.
Cmax of Venetoclax
时间窗: Approximately 29 days after first dose of study drug
Maximum observed plasma concentration (Cmax) for Venetoclax.
AUCt of Venetoclax
时间窗: Approximately 29 days after first dose of study drug
Area Under the Plasma Concentration-time Curve (AUC) from Time 0 to Time of the Last Measurable Concentration (AUCt)
AUC0-24 Post-dose of Venetoclax
时间窗: Approximately 29 days after first dose of study drug
Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of venetoclax.
Cmax of Dinaciclib
时间窗: Approximately 29 days after first dose of study drug
Maximum plasma concentration (Cmax) of dinaciclib.
Half-life (t1/2) of Dinaciclib
时间窗: Approximately 29 days after first dose of study drug
Half-life (t1/2) of dinaciclib.
AUCt Post-dose of Dinaciclib
时间窗: Approximately 29 days after first dose of study drug
Area under the plasma concentration-time curve from time zero to time t (AUCt) post-dose dinaciclib.
AUC0-∞ of Dinaciclib
时间窗: Approximately 29 days after first dose of study drug
Area under the plasma concentration-time curve from 0 to infinity (AUC0-∞) post-dose of dinaciclib.
Clearance of Dinaciclib
时间窗: Approximately 29 days after first dose of study drug
Clearance (CL) of dinaciclib.
次要结局
- Composite CR Rate (CR + CRi)(Up to approximately 18 months)
- Objective Response Rate (ORR)(Up to approximately 18 months)
- Complete Response (CR) Rate(Up to approximately 18 months)