A Phase Ia/b Dose Escalation and Expansion, Multicenter, Open-label, Safety, Pharmacokinetic and Pharmacodynamic Study of APTO-253 in Patients With Relapsed or Refractory Acute Myelogenous Leukemia or High-Risk Myelodysplasia
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 21
- 试验地点
- 13
- 主要终点
- Maximum tolerated dose and dose limiting toxicities
研究概览
简要总结
This study is being done to evaluate the safety and effectiveness of APTO-253 for the treatment of patients with the condition of acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) for which either the standard treatment has failed, is no longer effective, or can no longer be administered safely or poses a risk for your general well being.
详细描述
This is a multicenter, open-label, Phase Ia/b dose escalation study of safety, pharmacodynamics, and pharmacokinetics of APTO-253 in ascending cohorts (3+3 design) to determine the MTD or recommended dose in patients with relapsed or refractory acute myelogenous leukemia (AML) or high-risk MDS patients. This is to be followed by a cohort expansion phase at the MTD or recommended dose.
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
- •Patients ≥18 years old
- •Life expectancy of at least 2 months
- •Off previous cancer therapy for at least 14 days, or 5 half-lives for noncytotoxic agents prior to first study treatment administration
- •Patients must have a calculated creatinine clearance >60 mL/min
- •Acceptable hematologic, renal and liver functions and coagulation status parameters
排除标准
- •Patients with GVHD requiring systemic immunosuppressive therapy
- •Uncontrolled leptomeningeal disease, auto-immune hemolytic anemia and uncontrolled and clinical significant disease related metabolic disorder
- •Clinically significant intravascular coagulation
- •Treatment with other investigational drugs within 14 days prior to first study treatment administration
研究组 & 干预措施
Dose Escalation and Expansion
APTO-253 will be given in ascending doses in patients with relapsed or refractory AML or high risk MDS (escalation cohort), until the maximum tolerated dose or recommended dose is reached. Followed by up to 30 patients enrolled in the expansion cohort at the recommended dose.
干预措施: APTO-253 (Drug)
结局指标
主要结局
Maximum tolerated dose and dose limiting toxicities
时间窗: Cycle 1 (28 days)
To determine the maximum tolerated dose (MTD) and the dose limiting toxicities (DLT) of APTO-253 when given on days 1, 8, 15, and 22 of each 28-day cycle.
Incidence of treatment-emergent adverse events of APTO-253
时间窗: Cycle 1 (28 days)
To determine the safety and tolerability of APTO-253 by assessing treatment-related adverse events as assessed by CTCAE v4.0.
Establish recommended dose for future development of APTO-253
时间窗: Up to 7 months
To establish the dose of APTO-253 recommended for future development of APTO-253 for patients with specific types of hematologic malignancies.
次要结局
- Assess for any evidence of antitumor activity of APTO-253 by hematologic and bone marrow evaluations in acute leukemia and MDS.(Average 2 Cycles (8 weeks))
- Pharmacokinetic variables including maximum plasma concentration (Cmax)(Cycle 1 (28 days))
- Pharmacokinetic variables including minimum plasma concentration (Cmin)(Cycle 1 (28 days))
- Pharmacokinetic variables including volume of distribution(Cycle 1 (28 days))
- Pharmacokinetic variables including Area Under the Curve (AUC)(Cycle 1 (28 days))
- Pharmacokinetic variables including clearance(Cycle 1 (28 days))
- Pharmacokinetic variables including serum half-life(Cycle 1 (28 days))
- Determine the ability of APTO-253 to alter the expression of pharmacodynamic biomarkers of drug effect.(Average 2 Cycles (8 weeks))