Phase 3 Study Comparing Daratumumab, Bortezomib and Dexamethasone (DVd) vs Bortezomib and Dexamethasone (Vd) in Subjects With Relapsed or Refractory Multiple Myeloma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 498
- 主要终点
- Progression-free Survival (PFS)
研究概览
简要总结
The purpose of this study is to assess the effects of administration of daratumumab when combined with VELCADE (bortezomib) and dexamethasone compared with bortezomib and dexamethasone alone, for participants with relapsed or refractory multiple myeloma.
详细描述
This is an open-label (physicians and participants know the identity of the assigned treatment), randomized (the study medication is assigned by chance), multicenter, active-controlled study comparing daratumumab, VELCADE, and dexamethasone (DVd) with VELCADE and dexamethasone (Vd) in participants with relapsed or refractory multiple myeloma. Approximately 480 participants will be randomly assigned in a 1:1 ratio to receive either DVd or Vd. Randomization will be stratified by International Staging System (ISS), number of prior treatment programs (1 vs. 2 or 3 vs. >3), and prior VELCADE treatment ("no" vs. "yes"). Within each stratum, participants will be randomized to one of the treatment groups.The study will consist of a Screening Phase, a Treatment Phase, and a Follow-up Phase. Participants will be treated until disease progression, unacceptable toxicity, or other reasons to discontinue the study.
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
- •Must have had documented multiple myeloma
- •Must have received at least 1 prior line of therapy for multiple myeloma
- •Must have had documented evidence of progressive disease as defined based on Investigator's determination of response of International Myeloma Working Group (IMWG) criteria on or after their last regimen
- •Must have an Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2
- •Must have achieved a response (partial response [PR] or better based on investigator's determination of response by the IMWG criteria) to at least 1 prior regimen in the past
排除标准
- •Has received daratumumab or other anti-CD38 therapies previously
- •Is refractory to VELCADE or another PI, like ixazomib and carfilzomib (had progression of disease while receiving VELCADE therapy or within 60 days of ending VELCADE therapy or another PI therapy, like ixazomib and carfilzomib
- •Is intolerant to VELCADE (ie, discontinued due to any adverse event while on VELCADE treatment)
- •Has received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the date of randomization. The only exception is emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 milligram per day [mg/day] for a maximum of 4 days) before treatment. A list of anti-myeloma treatments with the corresponding pharmacokinetic half-lives is provided in the Site Investigational Product Procedures Manual (IPPM).
- •Has a history of malignancy (other than multiple myeloma) within 3 years before the date of randomization
- •Has any concurrent medical condition or disease (eg, active systemic infection) that is likely to interfere with study procedures
研究组 & 干预措施
Daratumumab+VELCADE+dexamethasone
Daratumumab, VELCADE and dexamethasone
干预措施: Daratumumab (Drug)
Daratumumab+VELCADE+dexamethasone
Daratumumab, VELCADE and dexamethasone
干预措施: VELCADE (Bortezomib) (Drug)
Daratumumab+VELCADE+dexamethasone
Daratumumab, VELCADE and dexamethasone
干预措施: Dexamethasone (Drug)
VELCADE+dexamethasone
VELCADE and dexamethasone.
干预措施: VELCADE (Bortezomib) (Drug)
VELCADE+dexamethasone
VELCADE and dexamethasone.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: From the date of randomization to either progressive disease or death, whichever occurred first (approximately 1 year 4 months)
PFS was defined as duration from date of randomization to either progressive disease (PD)/death, whichever occurred first. PD was defined as meeting any one of following criteria: Increase of greater than equal to (\>=)25 percent (%) in level of serum M-protein from lowest response value and absolute increase must be \>=0.5 gram per deciliter (g/dL); Increase of \>=25% in 24-hour urinary light chain excretion (urine M-protein) from lowest response value and absolute increase must be \>=200 mg/24hours; Only in participants without measurable serum and urine M-protein levels: increase of \>=25% in difference between involved and uninvolved FLC levels from lowest response value and absolute increase must be \>10 mg/dL; Definite increase in size of existing bone lesions or soft tissue plasmacytomas; Definite development of new bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium \>11.5 mg/dL) that can be attributed solely to PC proliferative disorder.
次要结局
- Percentage of Participants With a Very Good Partial Response (VGPR) or Better(Up to disease progression (approximately 6 years 9 months))
- Overall Response Rate (ORR)(Up to disease progression (approximately 6 years 9 months))
- Overall Survival (OS)(Up to 6 years 9 months)
- Time to Disease Progression (TTP)(From the date of randomization to the date of first documented evidence of progression or death due to PD whichever occurred first (approximately 6 years 9 months))
- Percentage of Participants With Negative Minimal Residual Disease (MRD)(Up to disease progression (approximately 6 years 9 months))