Phase 1b Study of Venetoclax and AMG 176 in Patients With Relapsed/Refractory Hematologic Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 9
- 试验地点
- 17
- 主要终点
- Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RPTD) for Venetoclax + AMG 176
研究概览
简要总结
This dose-escalation study evaluating the safety, pharmacokinetics and preliminary efficacy of venetoclax in combination with AMG 176 in participants with relapsed or refractory acute myeloid leukemia (AML) and participants with Non-Hodgkin's lymphoma (NHL)/diffuse large B-cell lymphoma (DLBCL).
This study will include a dose escalation phase to identify the maximum tolerated dose/recommended phase 2 dose (MTD/RPTD) of venetoclax plus AMG 176 as well as a dose expansion phase to confirm safety, explore efficacy, and confirm the suitability of the preliminary RPTD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- •Adequate kidney, liver and hematology values as described in the protocol.
- •Diagnosis of relapsed or refractory (R/R) acute myeloid leukemia (AML) or R/R Non-Hodgkin's lymphoma (NHL)/diffuse large B-cell lymphoma (DLBCL) confirmed by the World Health Organization (WHO) criteria, as appropriate.
- •Meets the following disease activity criteria:
- •AML: must have received at least 1 prior therapy for AML and be ineligible for cytotoxic therapy and allogeneic stem cell transplant.
- •NHL/DLBCL: measurable disease with a bidimensional lesion measuring at least 1.5 cm; received at least 1 prior therapy for NHL with no curative treatment option as determined by the investigator and be ineligible for a stem cell transplant.
排除标准
- •History of clinically significant medical condition that, in the opinion of the investigator, would adversely affect participation in this study.
- •History of 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 or autologous stem cell transplant within 100 days of study drug administration and no signs or symptoms of acute or chronic graft-versus-host disease.
- •Previous enrollment in a randomized trial including either venetoclax or AMG
- •Known active or chronic pancreatitis; severe chronic obstructive pulmonary disease with hypoxemia; central nervous system manifestations of malignancy.
- •Active, uncontrolled infection.
研究组 & 干预措施
Venetoclax + AMG 176
Venetoclax and AMG 176 will be administered in combination. Different combinations of dose levels for venetoclax and AMG 176 will be explored.
干预措施: Venetoclax (Drug)
Venetoclax + AMG 176
Venetoclax and AMG 176 will be administered in combination. Different combinations of dose levels for venetoclax and AMG 176 will be explored.
干预措施: AMG 176 (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RPTD) for Venetoclax + AMG 176
时间窗: Up to 28 days after first dose of study drug in a dose-escalation phase
The MTD and/or RPTD of venetoclax and of AMG 176 will be determined during the dose escalation phase of the study.
Number of Participants With Adverse Events
时间窗: From first dose of study drug until 30 days or 5 half-lives after discontinuation of study drug administration will be collected (up to approximately 4 years).
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
次要结局
- Maximum Plasma Concentration (Cmax) of Venetoclax(Up to approximately 28 days after first dose of study drug)
- Composite Complete Remission Rate (CRc) for Participants with AML(Up to approximately 2 years from last subject first dose)
- Objective Response Rate (ORR) for Participants with AML(Up to approximately 2 years from last subject first dose)
- ORR for Participants with NHL(Up to approximately 2 years from last subject first dose)
- Half-life (t1/2) of AMG 176(Approximately 16 days after first dose of study drug)
- AUC of Venetoclax(Up to approximately 28 days after first dose of study drug)
- Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax(Up to approximately 28 days after first dose of study drug)
- Maximum Plasma Concentration (Cmax) of AMG 176(Up to approximately 16 days after first dose of study drug)
- AUC of AMG 176(Approximately 16 days after first dose of study drug)
- Clearance (CL) of AMG 176(Approximately 16 days after first dose of study drug)