A Phase IIa Study Evaluating the Pharmacokinetics, Safety and Efficacy of APG-115 as a Single Agent or in Combination With APG-2575 in Subjects With Relapsed/Refractory T-Cell Prolymphocytic Leukemia (R/R T-PLL) or Non-Hodgkin's Lymphoma (NHL).
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 78
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose of APG-115
研究概览
简要总结
The goal of this study is to evaluate the pharmacokinetics (PK), safety, and efficacy of APG-115 as a single agent or in combination with APG-2575 in patients with T-PLL and NHL.
详细描述
This is a phase IIa, open-label, multi-center, clinical trial of interfering the binding of MDM2 oncoprotein with the tumor suppressor P53 protein, leads to increased P53 and P21 protein expression and activates P53-mediated apoptosis. The hypothesis is that APG-115 monotherapy and in combination with APG-2575 will shows good safety and efficacy in patients with R/R T-PLL and NHL
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Age ≥ 18 years old
- •Patients with relapsed/refractory T-PLL who have active disease and have received at least one prior therapy; Patients with histologically confirmed diagnosis of NHL, NHL Patients must be either relapsed, refractory, intolerant, or are considered ineligible for therapies known to provide clinical benefit;
- •Patients must not have had chemotherapy or antibody therapy for 7 days prior to starting APG-115 and/or APG-
- •However, patients with rapidly proliferative disease may receive hydroxyurea or decadron until 24 hours prior to starting therapy on this protocol.
- •Absolute neutrophil count (ANC) ≥ 500/mm˄3; hemoglobin ≥ 60 g/L; platelet count ≥ 30,000/mm˄3
- •Patients with adequate organ function;
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
- •Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient or his/her legally authorized representative is required prior to their enrollment on the protocol.
排除标准
- •Patient previously treated with a murine double minute 2 (MDM2) inhibitor.
- •Known active, uncontrolled central nervous system (CNS) malignancy
- •Patients require graft versus host therapy, or require continued treatment with systemic immunosuppressive agents (calcineurin inhibitors within 4 weeks prior to the first dose of study drug).
- •Patients who have any conditions or illness that, according to the opinions of the Investigators or the medical monitor, would compromise patient safety or interfere with the evaluation of safety and efficacy to the study drug(s).
- •Patients who have used strong CYP2C8 inhibitors, or moderate or strong CYP3A4 inhibitors or inducers within washout period of 14 days or 7 half-lives before the first administration of study drugs, whichever is longer.
研究组 & 干预措施
APG-115 monotherapy part
APG-115 will be given alone
干预措施: APG-115 (Drug)
APG-115 + APG-2575 combination dose escalation part
APG-115 is given in combination with APG-2575
干预措施: APG-115 (Drug)
APG-115 + APG-2575 combination dose escalation part
APG-115 is given in combination with APG-2575
干预措施: APG-2575 (Drug)
APG-115 + APG-2575 combination dose expansion part
APG-115 is given in combination with APG-2575
干预措施: APG-115 (Drug)
APG-115 + APG-2575 combination dose expansion part
APG-115 is given in combination with APG-2575
干预措施: APG-2575 (Drug)
结局指标
主要结局
Maximum tolerated dose of APG-115
时间窗: 21 days
To evaluate the safety of APG-115 as a single agent
Maximum tolerated dose of APG-115+APG-2575
时间窗: 21 days
To evaluate the maximum tolerated dose of APG-115 and APG-2575 in combination
次要结局
未报告次要终点