A Randomized, Blinded, Placebo-Controlled, Multicenter, Phase II Study of Bevacizumab in Combination With Bortezomib in Patients With Relapsed or Refractory Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 102
- 主要终点
- Progression-free Survival (PFS)
研究概览
简要总结
This is a randomized, blinded, placebo-controlled, multicenter, Phase II study designed to provide a preliminary assessment of the safety and efficacy of combining bevacizumab with bortezomib in patients with relapsed or refractory multiple myeloma.
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
- Single (Investigator)
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
- •Age ≥ 18 years
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- •Previously diagnosed with multiple myeloma
- •Relapsed or refractory multiple myeloma with disease progression following one to three prior treatment regimens
- •Measurable multiple myeloma disease
排除标准
- •Grade ≥ 2 peripheral neuropathy
- •Use of corticosteroids within 21 days prior to Day 1
- •Use of other anti-myeloma therapy within 21 days prior to Day 1
- •Intolerance to bortezomib or compounds containing boron
- •Life expectancy of < 12 weeks
- •Current, recent, or planned participation in an experimental drug study
- •Active malignancy other than multiple myeloma within 5 years before screening
- •Prior treatment with bevacizumab
- •Inadequately controlled hypertension
- •Prior history of hypertensive crisis or hypertensive encephalopathy
- •New York Heart Association (NYHA) Class II or greater congestive heart failure (CHF)
- •Decreased left ventricular function at study entry
- •History of myocardial infarction or unstable angina within 6 months prior to Day 1
- •History of stroke or transient ischemic attack within 6 months prior to Day 1
- •Significant vascular disease or recent peripheral arterial thrombosis within 6 months prior to Day 1
- •Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1, or anticipation of need for major surgical procedure during the course of the study
- •Core biopsy or other minor surgical procedure, including placement of a vascular access device within 7 days prior to Day 1
- •History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1
- •Serious, non-healing wound, active ulcer, or untreated bone fracture (for pathologic bone fractures consistent with multiple myeloma, patients may be eligible if no treatment is planned)
- •Albuminuria
- •Known hypersensitivity to any component of bevacizumab
- •Pregnancy (positive pregnancy test) or lactation
研究组 & 干预措施
Bortezomib + bevacizumab
Participants received bortezomib 1.3 mg/m^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and bevacizumab 15 mg/kg administered by intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. After completion of 8 cycles, participants could continue to receive bevacizumab as monotherapy until disease progression.
干预措施: Bevacizumab (Drug)
Bortezomib + bevacizumab
Participants received bortezomib 1.3 mg/m^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and bevacizumab 15 mg/kg administered by intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. After completion of 8 cycles, participants could continue to receive bevacizumab as monotherapy until disease progression.
干预措施: Bortezomib (Drug)
Bortezomib + placebo
Participants received bortezomib 1.3 mg/m^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and placebo intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. At the completion of the 8-cycle treatment phase, participants entered the observation phase until disease progression.
干预措施: Bortezomib (Drug)
Bortezomib + placebo
Participants received bortezomib 1.3 mg/m^2 administered as a 3- to 5-second bolus intravenous injection on Days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles and placebo intravenous infusion on the first day of each 21-day cycle during the blinded treatment phase. At the completion of the 8-cycle treatment phase, participants entered the observation phase until disease progression.
干预措施: placebo (Drug)
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: From randomization to disease progression or death on study (up to 116 weeks).
Progression-free survival (PFS) was defined as the time from randomization to disease progression or death on study from any cause within 30 days of the last response assessment. Disease progression was determined by the investigator using the International Myeloma Working Group's (IMWG) uniform response criteria. Median PFS was estimated using Kaplan-Meier methodology. For patients who were alive at the time of the analysis and whose disease had not yet progressed, PFS was censored at the time of the last response assessment.
次要结局
- Percentage of Participants With an Overall Response(From randomization to the end of study (clinical cut-off; up to 116 weeks).)
- Duration of Response(From randomization to the end of study (clinical cut-off; up to 116 weeks).)
- Overall Survival (OS)(From randomization until death from any cause, up until the end of study (clinical cut-off; up to 116 weeks).)
- Number of Participants With Selected Adverse Events (AEs)(Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination (up to 122 weeks).)
- Number of Participants With an Overall Response(From randomization to the end of study (clinical cut-off; up to 116 weeks).)