Phase 1b Study of Venetoclax and Alvocidib in Patients With Relapsed/Refractory Acute Myeloid Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 36
- 试验地点
- 14
- 主要终点
- AUC0-24 Post-dose of Venetoclax
研究概览
简要总结
An open-label, dose-escalation study to assess the safety and pharmacokinetics (PK), to determine the dose limiting toxicity (DLT) and the recommended Phase 2 dose (RPTD), and to assess the preliminary efficacy of alvocidib with venetoclax when co-administered in participants with relapsed or refractory (R/R) acute myeloid leukemia (AML).
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
- •Must have adequate coagulation, hematology, kidney, and liver function, per protocol.
- •Diagnosis of relapsed or refractory (R/R) acute myeloid leukemia (AML)
- •Meet the following disease activity criteria:
- •an established, confirmed diagnosis of AML by World Health Organization criteria excluding acute promyelocytic leukemia (APL)-M3; and
- •an Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to
- •If male participant is sexually active, he must agree from day 1 through 6 months after the last dose of alvocidib or 90 days after the last dose of venetoclax, whichever is longer, to practice the protocol-specified protection.
排除标准
- •History of any malignancy within the last 6 months except for those specified in this protocol and low-grade malignancies not requiring active treatment such as non-melanoma skin cancer, cervical intraepithelial neoplasia, or prostate cancer in situ.
- •Prior allogeneic stem cell transplant within 6 months of study drug administration and no requirement for graft versus host therapy.
- •History of previous enrollment in Studies NCT02993523 or NCT
- •History of exposure to alvocidib or any other cyclin-dependent kinase 9 (CDK9) inhibitor.
- •History of Tumor Lysis Syndrome (TLS) due to previous exposure to venetoclax.
研究组 & 干预措施
Venetoclax + Alvocidib
Venetoclax administered orally once daily (QD) and Alvocidib administered as an intravenous infusion on Days 1, 2, and 3 for all 28-day treatment cycles. Different combinations of dose levels for venetoclax and alvocidib may be explored.
干预措施: Venetoclax (Drug)
Venetoclax + Alvocidib
Venetoclax administered orally once daily (QD) and Alvocidib administered as an intravenous infusion on Days 1, 2, and 3 for all 28-day treatment cycles. Different combinations of dose levels for venetoclax and alvocidib may be explored.
干预措施: Alvocidib (Drug)
结局指标
主要结局
AUC0-24 Post-dose of Venetoclax
时间窗: Approximately 32 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 Alvocidib
时间窗: Approximately 32 days after first dose of study drug
Maximum plasma concentration (Cmax) of alvocidib.
Half-life (t1/2) of Alvocidib
时间窗: Approximately 32 days after first dose of study drug
Half-life (t1/2) of alvocidib
AUCt Post-dose of Alvocidib
时间窗: Approximately 32 days after first dose of study drug
Area under the plasma concentration-time curve from time zero to time t (AUCt) post-dose alvocidib.
Tmax of venetoclax
时间窗: Approximately 32 days after first dose of study drug
Time to maximum plasma concentration (Tmax) of venetoclax
Clearance of Alvocidib
时间窗: Approximately 32 days after first dose of study drug
Clearance (CL) of alvocidib
AUC0-∞ of Alvocidib
时间窗: Approximately 32 days after first dose of study drug
Area under the plasma concentration-time curve from 0 to infinity (AUC0-∞) post-dose of alvocidib
Cmax of Venetoclax
时间窗: Approximately 32 days after first dose of study drug
Maximum plasma concentration (Cmax) of venetoclax
Dose Escalation Phase: Recommended Phase 2 dose (RPTD) for Venetoclax and Alvocidib
时间窗: Minimum first cycle of dosing (up to 28 days)
RPTD will be determined using available safety and pharmacokinetics data upon completion of the dose escalation phase.
次要结局
- Complete Response (CR) Rate(Up to approximately 8 months)
- Combined CR Rate(Up to approximately 8 months)
- Objective Response Rate (ORR)(Up to approximately 18 months)