A Randomized, Open-label Phase 3 Study of Carfilzomib, Melphalan, and Prednisone Versus Bortezomib, Melphalan, and Prednisone in Transplant-ineligible Patients With Newly Diagnosed Multiple Myeloma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 955
- 试验地点
- 212
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
The primary objective was to compare the progression-free survival of transplant ineligible patients newly diagnosed with multiple myeloma who were treated with carfilzomib, melphalan and prednisone (CMP) or with Velcade® (bortezomib), melphalan and prednisone (VMP).
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Newly diagnosed symptomatic multiple myeloma (per International Myeloma Working Group [IMWG] diagnostic criteria)
- •Transplant ineligibility
- •Measurable disease, as defined by 1 or more of the following (assessed within 21 days prior to randomization):
- •Serum M-protein ≥ 0.5 g/dL, or
- •Urine M-protein ≥ 200 mg/24 hours, or
- •In subjects without detectable serum or urine M-protein, serum free light chain (SFLC) > 100 mg/L (involved light chain) and an abnormal kappa lambda ratio (SFLC kappa lambda ratio < 0.26 or > 1.65)
- •No prior treatment for multiple myeloma
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
排除标准
- •Multiple myeloma of IgM (immunoglobulin M) subtype
- •Glucocorticoid therapy within 14 days prior to randomization that equals or exceeds a cumulative dose of 160 mg of dexamethasone
- •POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- •Plasma cell leukemia (> 2.0 × 10^9/L circulating plasma cells by standard differential)
- •Waldenström macroglobulinemia (WM)
- •Known amyloidosis
研究组 & 干预措施
Carfilzomib, Melphalan, Prednisone
Participants received carfilzomib administered in combination with melphalan and prednisone for nine 42-day cycles. Carfilzomib was administered as an intravenous (IV) infusion on days 1, 2, 8, 9, 22, 23, 29, and 30 of each 42-day cycle. The carfilzomib dose was at 20 mg/m² on cycle 1, days 1 and 2 followed by 36 mg/m² thereafter. On days 1 to 4, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².
干预措施: Melphalan (Drug)
Carfilzomib, Melphalan, Prednisone
Participants received carfilzomib administered in combination with melphalan and prednisone for nine 42-day cycles. Carfilzomib was administered as an intravenous (IV) infusion on days 1, 2, 8, 9, 22, 23, 29, and 30 of each 42-day cycle. The carfilzomib dose was at 20 mg/m² on cycle 1, days 1 and 2 followed by 36 mg/m² thereafter. On days 1 to 4, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².
干预措施: Carfilzomib (Drug)
Carfilzomib, Melphalan, Prednisone
Participants received carfilzomib administered in combination with melphalan and prednisone for nine 42-day cycles. Carfilzomib was administered as an intravenous (IV) infusion on days 1, 2, 8, 9, 22, 23, 29, and 30 of each 42-day cycle. The carfilzomib dose was at 20 mg/m² on cycle 1, days 1 and 2 followed by 36 mg/m² thereafter. On days 1 to 4, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².
干预措施: Prednisone (Drug)
Bortezomib, Melphalan, Prednisone
Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².
干预措施: Bortezomib (Drug)
Bortezomib, Melphalan, Prednisone
Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².
干预措施: Melphalan (Drug)
Bortezomib, Melphalan, Prednisone
Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².
干预措施: Prednisone (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: From randomization until the data cut-off date of 15 July 2016; median follow-up time for PFS was 21.6.and 22.2 months in the bortezomib and carfilzomib arms respectively.
Progression-free survival was defined as the time from randomization to the earlier of documented disease progression or death due to any cause. PFS was analyzed using Kaplan-Meier methods. The duration of PFS was censored for participants with no baseline and/or post-baseline disease assessments, who started a new anti-cancer therapy before documentation of disease progression or death, death or disease progression after missed disease assessment of 100 consecutive days or longer, or who were alive without documentation of disease progression before the data cutoff date, including lost to follow-up prior to disease progression. Participants were evaluated for disease response and progression according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC), determined centrally using a validated computer algorithm in a blinded manner.
次要结局
- Overall Survival (OS)(From randomization until the data cut-off date of 15 July 2016; median follow-up time for OS was 22.2 and 22.5 months in the bortezomib and carfilzomib arms respectively.)
- Overall Response Rate(Disease response was assessed every 3 weeks during the first 54 weeks and every 6 weeks thereafter until PD or the data cut-off date of 15 July 2016; median follow-up time was 21.6.and 22.2 months in the bortezomib and carfilzomib arms respectively.)
- Complete Response Rate(Disease response was assessed every 3 weeks during the first 54 weeks and every 6 weeks thereafter until PD or the data cut-off date of 15 July 2016; median follow-up time was 21.6.and 22.2 months in the bortezomib and carfilzomib arms respectively.)
- Percentage of Participants With ≥ Grade 2 Peripheral Neuropathy(From the first dose of any study drug up to 30 days after the last dose of any study drug as of the data cut-off date of 15 July 2016; median duration of treatment was 52 weeks in both treatment groups.)
- European Organisation for Research and Treatment of Cancer Quality of Life Core Module (EORTC QLQ-C30) Global Health Status/Quality of Life (QOL) Scores(Baseline, weeks 6, 12, 18, 24, 30, 36, 42 and 48)
- Number of Participants With Adverse Events(From the first dose of any study drug up to 30 days after the last dose of any study drug as of the data cut-off date of 15 July 2016; median duration of treatment was 52 weeks in both treatment groups.)