An Open Label, Dose Escalation, Multicenter Phase 1/2 Study of KW-2478 in Combination With Bortezomib in Subjects With Relapsed and/or Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 95
- 试验地点
- 26
- 主要终点
- To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2).
研究概览
简要总结
The purpose of this study is to assess the safety and benefits of the investigational study drug, KW-2478, when given with bortezomib (Velcade®), a drug approved for the treatment of Multiple Myeloma (MM).
The primary objectives:
- To establish the safety, tolerability, and recommended Phase II dose (RP2D) of KW-2478 in combination with bortezomib (Phase I);
- To assess the overall response rate (ORR) when subjects with advanced MM are treated (Phase II).
The secondary objectives:
- To characterize the Pharmacokinetic (PK) and Pharmacodynamic (PD) of KW-2478 with bortezomib (Phase I only);
- To evaluate for preliminary evidence of efficacy (Phase I);
- To determine progression free survival (PFS) and duration of response of KW-2478 with bortezomib (Phase II).
详细描述
This is a multicenter, open label, dose escalation, Phase I / II study in subjects with relapsed and/or refractory MM. Up to 24 subjects to be enrolled in the Phase I to determine the RP2D. Up to 77 additional evaluable subjects to be enrolled in Phase II for a maximum up to 101 subjects treated in the study. Study centers in the USA and the UK will participate in Phase I and II. Centers in the Philippines will be participating in Phase II only. The planned enrollment period is 22 months and the planned study duration is 28 months.
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 a confirmed diagnosis of Multiple Myeloma who have had one and no more than three prior regimens for MM to which they did not respond (failed) or from which they have relapsed.
- •Signed either an IRB or IEC approved informed consent
- •ECOG performance status of ≤ 2
- •Life expectancy of at least 3 months
- •M protein in either serum or urine, or free light chains if not measurable M protein in serum or urine, and clonal bone marrow plasma cells > 10%, and evidence of end organ damage
- •Adequate hematologic status, liver and renal function
- •Subjects of reproductive potential must agree to follow accepted pregnancy prevention methods during the study.
排除标准
- •No anti-cancer treatment for ≥ 4 weeks and no bortezomib treatment ≥ 60 days prior to receiving study drug
- •Any other severe, acute or chronic illness
- •No other prior or concurrent malignancy
- •No immunosuppressant therapy
研究组 & 干预措施
Phase 1: Cohort 1
Cohort 1: KW 2478 130 mg/m^2 and Bortezomib 1.0 mg/m^2
干预措施: KW-2478 (Drug)
Phase 1: Cohort 1
Cohort 1: KW 2478 130 mg/m^2 and Bortezomib 1.0 mg/m^2
干预措施: Bortezomib (Drug)
Phase 1: Cohort 2
Cohort 2: KW 2478 130 mg/m^2 and Bortezomib 1.3 mg/m^2
干预措施: KW-2478 (Drug)
Phase 1: Cohort 2
Cohort 2: KW 2478 130 mg/m^2 and Bortezomib 1.3 mg/m^2
干预措施: Bortezomib (Drug)
Phase 1: Cohort 3
Cohort 3: KW 2478 175 mg/m^2 and Bortezomib 1.0 mg/m^2
干预措施: KW-2478 (Drug)
Phase 1: Cohort 3
Cohort 3: KW 2478 175 mg/m^2 and Bortezomib 1.0 mg/m^2
干预措施: Bortezomib (Drug)
Phase 1: Cohort 4
Cohort 4: KW 2478 175 mg/m^2 and Bortezomib 1.3 mg/m^2
干预措施: KW-2478 (Drug)
Phase 1: Cohort 4
Cohort 4: KW 2478 175 mg/m^2 and Bortezomib 1.3 mg/m^2
干预措施: Bortezomib (Drug)
Phase 2
KW 2478 175 mg/m^2 and Bortezomib 1.0 mg/m^2
干预措施: KW-2478 (Drug)
Phase 2
KW 2478 175 mg/m^2 and Bortezomib 1.0 mg/m^2
干预措施: Bortezomib (Drug)
结局指标
主要结局
To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2).
时间窗: 21 day cycle, up to 52 weeks
The safety of KW-2478 was determined by reported TEAEs, observed DLTs, changes in PEs, vital sign measurements, ECGs, and laboratory analyses. The ORR, was defined as the best response over a specified number of cycles (calculated and summarized). Disease control rate (DCR) was defined as the best response over a specified number of cycles (calculated and summarized). Progression-free survival was defined as the time from the first day of treatment until the date of disease progression or death is first reported (calculated and summarized).
次要结局
- Phase 1: PK Exposure Cmax ng/mL Day 11(PK collected Day 11 of 21-day cycle)
- Phase 1: PK Absorption Tmax hr Day 11(PK collected Day 11 of 21-day cycle)
- Phase 1: PK Exposure AUC0-t hr*ng/mL Day 11(PK collected Day 11 of 21-day cycle)
- Phase 1: PK Elimination t½ hr Day 11(PK collected Day 11 of 21-day cycle)