Phase 1 Ascending Multiple-Dose Study to Evaluate the Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) of BMS-906024 in Subjects With Relapsed/Refractory T-cell Acute Lymphoblastic Leukemia or T-cell Lymphoblastic Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 31
- 试验地点
- 5
- 主要终点
- Number of subjects with adverse events as a measure of safety and tolerability
研究概览
简要总结
The purpose of this study is to identify a safe and tolerable dose of BMS-906024, either alone or in combination with Dexamethasone in subjects with T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma who no longer respond to or have relapsed from standard therapies
详细描述
Minimum Age: 10 years and older at selected sites
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Subjects with T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma refractory to or relapsed from standard therapies
- •Life expectancy of at least 2 months
- •Performance status (PS) 0-1 (a measure of the ability to carry out activities of daily living); subjects with PS 2 are eligible if due to disease related symptoms
- •Prior anti-cancer treatment permitted (with specific criteria)
- •Adequate organ function
排除标准
- •Infection
- •Elevated triglycerides
- •Gastro-intestinal disease with increased risk of diarrhea (e.g. inflammatory bowel disease)
- •Unable to tolerate bone marrow biopsy
- •Taking medications known to increase risk of Torsades De Pointes (an abnormal heart rhythm)
研究组 & 干预措施
Escalation Phase: BMS-906024
BMS-906024 escalating doses starting at 0.3 mg solution for intravenous (IV) administration once weekly continuously until disease progression or unacceptable toxicity
干预措施: BMS-906024 (Drug)
Expansion Phase: BMS-906024 + Dexamethasone
BMS-906024 maximum tolerated dose (To be determined) solution for IV administration once weekly and Dexamethasone 20mg/day tablet by mouth (Oral) for 3-4 days every week for 3-4 weeks per cycle continuously until disease progression or unacceptable toxicity
干预措施: BMS-906024 (Drug)
Expansion Phase: BMS-906024 + Dexamethasone
BMS-906024 maximum tolerated dose (To be determined) solution for IV administration once weekly and Dexamethasone 20mg/day tablet by mouth (Oral) for 3-4 days every week for 3-4 weeks per cycle continuously until disease progression or unacceptable toxicity
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Number of subjects with adverse events as a measure of safety and tolerability
时间窗: Weekly assessments until study discontinuation due to disease progression or unacceptable adverse events as well as an assessment 30 days after treatment discontinuation with an average time on study expected to be < 1 year.
次要结局
- Disease assessments in bone marrow & by computed tomography (CT)/ magnetic resonance imaging (MRI)(Disease assessments at least every 8 weeks during treatment)
- Pharmacokinetics of BMS-906024 and its metabolite BMS-911557: maximum observed concentration (Cmax)(Pharmacokinetics at multiple time points during the first 4 weeks of dosing)
- Pharmacokinetics of BMS-906024 and its metabolite BMS-911557: minimum observed concentration (Cmin)(Pharmacokinetics at multiple time points during the first 4 weeks of dosing)
- Pharmacokinetics of BMS-906024 and its metabolite BMS-911557: area under the concentration-time curve (AUC)(Pharmacokinetics at multiple time points during the first 4 weeks of dosing)
- Pharmacokinetics of BMS-906024 and its metabolite BMS-911557: time to reach maximum observed concentration (Tmax)(Pharmacokinetics at multiple time points during the first 4 weeks of dosing)
- Pharmacokinetics of BMS-906024 and its metabolite BMS-911557: terminal phase elimination half-life (T-Half)(Pharmacokinetics at multiple time points during the first 4 weeks of dosing)
- Pharmacokinetics of BMS-906024 and its metabolite BMS-911557: accumulation index (ratio of AUC at steady state to AUC after first dose)(Pharmacokinetics at multiple time points during the first 4 weeks of dosing)
- Pharmacodynamics (percent change from baseline in mRNA expression of Notch pathway-related genes in blood cells)(Pharmacodynamic sampling: in blood during the first 8 weeks of dosing)