A Phase 1, Open-label, Dose-escalation Study of Dasatinib and All-Trans Retinoic Acid for Relapsed/Refractory and/or Elderly Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- To determine the MTD and DLTs of dasatinib in combination with ATRA given the proposed dose escalation plan.
研究概览
简要总结
This is an open label, prospective, single institution dose-escalation study. The patient population includes non-induction candidate elderly patients with AML or MDS and/or patients with high-risk or relapsed/refractory AML or MDS. Five dose cohorts will be evaluated using a fixed dose of ATRA in combination with an escalating dose of dasatinib. The investigators will treat with an escalating dose of dasatinib from 70mg to 140mg daily. Dose escalation will proceed in a standard 3+3 fashion. A de-escalation to a 50 mg total daily dose of dasatinib is planned if DLT is greater than or equal to 33% is observed at the first dose level. Once the MTD for the combination of the drugs has been established, up to 6 additional patients will be enrolled at the MTD level to obtain additional safety information about the combination and to allow for preliminary laboratory correlate analysis.
详细描述
Primary Objective:
- To determine the safety and tolerability of the combination of dasatinib and ATRA in relapsed or elderly, non-induction candidate acute myelogenous leukemia (AML) or MDS patients and to identify the maximally tolerated dose (MTD), dose-limiting toxicities (DLT).
Secondary Objectives:
- To determine the pharmacokinetic (PK) profiles of dasatinib and ATRA when administered as combination therapy for patients with AML or MDS
- To determine if the combination therapy of dasatinib and ATRA promotes differentiation of AML or MDS .
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
- 未提供
排除标准
- •Prisoners, or subjects who are involuntarily incarcerated. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
研究组 & 干预措施
dasatinib (SPRYCEL) and all trans retinoic acid (VESANOID)
Dasatinib DL0 - 50 mg every 24 hours DL1 (START)- 70 mg every 24 hours DL2 - 100 mg every 24 hours DL3 - 140 mg every 24 hours
ATRA 22.5mg/m2 every 12 hours
干预措施: dasatinib (SPRYCEL) (Drug)
dasatinib (SPRYCEL) and all trans retinoic acid (VESANOID)
Dasatinib DL0 - 50 mg every 24 hours DL1 (START)- 70 mg every 24 hours DL2 - 100 mg every 24 hours DL3 - 140 mg every 24 hours
ATRA 22.5mg/m2 every 12 hours
干预措施: all trans retinoic acid (VESANOID) (Drug)
结局指标
主要结局
To determine the MTD and DLTs of dasatinib in combination with ATRA given the proposed dose escalation plan.
时间窗: 1.5 years
次要结局
- Assessment of Differentiation. Bone marrow biopsies and aspirates will be obtained pre-treatment, on day 14, and day 28. These will be subjected to morphologic, cytochemical, and routine flow cytometric analyses.(1.5 years)
- Assess treatment effects on SFK (Src family kinase) activation and expression of RARA target genes.(1.5 years)
- PK parameters including peak concentration (Cmax),Tmax, Cmin, the area under the curve (AUC), volume of distribution, clearance terms, elimination rate constant, and elimination half-life (t1/2) will be analyzed.(1.5 years)