A Phase 1a/b Trial of CG-806 in Patients With Relapsed/Refractory Acute Myeloid Leukemia or Higher-Risk Myelodysplastic Syndromes
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 45
- 试验地点
- 10
- 主要终点
- Incidence of treatment-emergent adverse events of CG-806
研究概览
简要总结
This study is being done to evaluate the safety, tolerability and antitumor activity of oral CG-806 (luxeptinib) for the treatment of patients with Acute Myeloid Leukemia (except APML), secondary AML, therapy-related AML, or higher-risk MDS, whose disease has relapsed, is refractory or who are ineligible for or intolerant of intensive chemotherapy or transplantation.
详细描述
This is a multicenter, open-label, Phase 1 a/b dose escalation study of safety, pharmacodynamics, and pharmacokinetics of CG-806 in ascending cohorts (3+3 design) to determine the MTD or recommended dose in patients with relapsed or refractory Acute Myeloid Leukemia (except APML), secondary AML, therapy-related AML, or higher-risk MDS whose disease has relapsed, is refractory or who are ineligible for or intolerant of intensive chemotherapy or transplantation. This is to be followed by a cohort expansion phase.
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
- •Age ≥18 years
- •Life expectancy of at least 3 months
- •ECOG Performance Status ≤ 2
- •Patients must be able to swallow capsules
- •Adequate hematologic parameters, unless cytopenias are disease caused
- •Adequate renal, liver and cardiac functions
排除标准
- •Patients with GVHD requiring systemic immunosuppressive therapy
- •Uncontrolled leptomeningeal disease, auto-immune hemolytic anemia and uncontrolled and clinically significant disease related metabolic disorder
- •Clinically significant leukostasis
- •Treatment with other investigational drugs or receipt of cytotoxic therapy within 14 days prior to first study treatment administration
- •Receipt of cellular immunotherapeutic agents within 4 weeks prior to first study treatment administration
研究组 & 干预措施
Dose Escalation and Expansion
Dose Escalation and Expansion; CG-806 will be given orally in ascending doses in patients with relapsed or refractory AML or higher-risk MDS (escalation cohort), until the maximum tolerated dose or candidate recommended Phase 2 dose is reached. Followed up by up to 50 patients enrolled in the expansion cohort at the recommended dose.
干预措施: CG-806 (Drug)
结局指标
主要结局
Incidence of treatment-emergent adverse events of CG-806
时间窗: At the end of Cycle 1 (each cycle is 28 days)
Patients will be assessed for adverse events during all cycles of treatment and for dose limiting toxicities in Cycle 1 (28-days). Dose escalation to a higher dose level will be considered if none of the first three patients who complete Cycle 1 (28-days) at a given dose level experience a dose limiting toxicity or if only 1 of 6 patients at a given dose level experience a dose-limiting toxicity.
Establish a CG-806 dose that maintains a biologically active plasma concentration
时间窗: At the end of Cycle 1 (each cycle is 28 days)
To determine the dose of CG-806 given orally every 12 hours daily that maintains a biologically active plasma concentration during 28-day cycles.
Establish a recommended dose for future development of CG-806
时间窗: At the end of Cycle 1 (each cycle is 28 days)
To establish the maximum tolerated dose and/or recommended Phase 2 dose (RP2D) of CG-806 for future clinical trials in patients with AML and other advanced myeloid malignancies.
次要结局
- Pharmacokinetics variables including volume of distribution(At the end of Cycle 1 (each cycle is 28 days))
- Pharmacokinetics variables including clearance(At the end of Cycle 1 (each cycle is 28 days))
- Pharmacokinetics variables including area under the curve (AUC)(At the end of Cycle 1 (each cycle is 28 days))
- To determine the ability of CG-806 to modulate the expression or activity of pharmacodynamic biomarkers of drug effect.(At the end of Cycle 1 (each cycle is 28 days))
- Pharmacokinetics variables including plasma half-life.(At the end of Cycle 1 (each cycle is 28 days))
- To determine the Relative Bioavailability of Generation 3 formulation given to up to 18 patients on Cycle 1 Day -3 compared to Generation 1 formulation of study drug given to patients during Cycle 1.(At the end of Cycle 1 (each cycle is 28 days))
- Pharmacokinetics variables including maximum plasma concentration (Cmax).(At the end of Cycle 1 (each cycle is 28 days))
- Pharmacokinetics variables including minimum plasma concentration (Cmin)(At the end of Cycle 1 (each cycle is 28 days))
- Compare G1 to G3 Pharmacokinetics variables including clearance(At the end of Cycle 1 (each cycle is 28 days))
- To assess patients for evidence of anti-tumor activity of CG-806 based on hematologic, bone marrow, physical examination, evaluations(At the end of Cycle 1 (each cycle is 28 days))
- To determine the Relative Bioavailability of Generation 3 formulation given to up to 18(At the end of Cycle 1 (each cycle is 28 days))