A Phase 1b, Multicenter, Open-Label, Dose Escalation Study of SAR245409 to Evaluate the Safety, Tolerability and Clinical Activity of SAR245409 in Combination With Rituximab or Bendamustine Plus Rituximab in Patients With Relapsed or Refractory Indolent B-cell Non-Hodgkin Lymphoma, Mantle Cell Lymphoma or Chronic Lymphocytic Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 37
- 试验地点
- 3
- 主要终点
- Identification Of Dose-Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD)
研究概览
简要总结
Primary Objective:
- To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) for SAR245409 when administered in combination with rituximab or bendamustine plus rituximab
Secondary Objectives:
- To determine the safety and tolerability of SAR245409 in combination with rituximab or bendamustine plus rituximab in subjects with indolent Hon-Hodgkin Lymphoma (iNHL) Mantle Cell Lymphoma (MCL) or Chronic Lymphocytic Leukemia (CLL)
- To determine the pharmacokinetics (PK) of SAR245409, bendamustine and rituximab when used in combination in subjects with iNHL, MCL or CLL
- To determine the pharmacodynamic (PD) effects of SAR245409 in combination with rituximab or bendamustine plus rituximab in subjects with iNHL, MCL or CLL
- To determine the antitumor activity of SAR245409 in combination with rituximab or bendamustine plus rituximab in subjects with iNHL, MCL or CLL
详细描述
All subjects will take SAR245409 twice daily. All subjects will receive SAR245409 as long as there is clinical benefit.
Combination therapy with SAR245409, bendamustine and rituximab , will be administered over a 28 day cycle for up to 6 to 8 cycles.
Subjects receiving the doublet combination , SAR245409 plus rituximab will receive weekly rituximab for 4 - 8 weeks. Monthly Rituximab may be continued beyond 8 weeks.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
SAR245409 + rituximab
Subjects will receive oral SAR245409 twice daily continuously and weekly rituximab intravenously
干预措施: SAR245409 (Drug)
SAR245409 + rituximab + bendamustine (iNHL, MCL)
Subjects will receive oral SAR245409 twice daily continuously and monthly bendamustine intravenously.
干预措施: SAR245409 (Drug)
SAR245409 + rituximab+ bendamustine (CLL)
Subjects will receive oral SAR245409 twice daily continuously and monthly bendamustine and rituximab intravenously
干预措施: SAR245409 (Drug)
结局指标
主要结局
Identification Of Dose-Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD)
时间窗: 4 weeks to 8 weeks
次要结局
- Pharmacokinetics (tmax) of bendamustine(up to 2 months)
- Pharmacokinetics (tmax) of rituximab(up to 2 months)
- Number of subjects with treatment emergent adverse events(Time from receiving first dose of SAR245409 until 30 days after the last dose)
- Pharmacokinetics (tmax) of SAR245409(up to 2 months)
- Pharmacokinetics (Ctrough) of SAR245409(up to 2 months)
- Pharmacokinetics (AUC) of bendamustine(up to 2 months)
- Pharmacokinetics (AUClast) of bendamustine(up to 2 months)
- Pharmacokinetics (Ceoi) of bendamustine(up to 2 months)
- Pharmacokinetics (AUC0-12h) of SAR245409(up to 2 months)
- Pharmacokinetics (Cmax) of SAR245409(up to 2 months)
- Pharmacokinetics (Vss) of bendamustine(up to 2 months)
- Efficacy as determined by objective response rate (ORR)(up to 4 years)
- Pharmacokinetics (Cl) of bendamustine(up to 2 months)
- Pharmacokinetics (AUC0-7h) of rituximab(up to 2 months)
- Pharmacokinetics (Ceoi) of rituximab(up to 2 months)