A Multicenter, Randomized, Double Blind, Placebo Controlled Phase III Study of Panobinostat in Combination With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 767
- 试验地点
- 1
- 主要终点
- Progression Free Survival in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone.
研究概览
简要总结
Panobinostat (LBH589) is a highly potent pan-deacetylase inhibitor (pan-DACi), inclusive of HDAC6, which disrupts aggresome function, promotes accumulation of cytotoxic misfolded protein aggregates and triggers myeloma cell death. Combination of pan-DAC and protease inhibition by co-treatment with panobinostat (PAN) and bortezomib (BTZ) has demonstrated synergistic cytotoxicity in vitro and in vivo in pre-clinical experiments. Furthermore, clinical experience in advanced multiple myeloma (MM) patients treated by oral panobinostat and i.v bortezomib ± dexamethasone showed very encouraging results for efficacy and manageable toxicity profile.
Given the medical need for improved treatment strategies for patients with previously treated and relapsed MM, the purpose of this prospective, multinational, randomized, double-blind, placebo-controlled, parallel group Phase III study is to compare the results in progression-free survival of 2 combination therapies, panobinostat with bortezomib and dexamethasone or placebo with bortezomib and dexamethasone, in patients with previously treated MM whose disease has recurred or progressed.
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
- Double (Participant, 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
- •Patient has a previous diagnosis of multiple myeloma.
- •Patient requires retreatment for multiple myeloma
- •Patient has measurable M component in serum or urine at study screening
排除标准
- •Patient who has progressed under all prior lines of anti MM therapy
- •Patient who has been treated by bortezomib before, and did not reach at least a minor response under this therapy, or progressed under it or within 60 days of last dose
- •Patient has shown intolerance to bortezomib or to dexamethasone or components of these drugs or has any contraindication to one or the other drug , following locally applicable prescribing information
- •Patient received prior treatment with DAC inhibitors including panobinostat
- •Patient has impaired cardiac function, or a prolonged QTc interval at screening ECG
- •Patient taking medications with relative risk of prolonging the QT interval or inducing Torsade de pointes
- •Female patient who is pregnant or breast feeding or with childbearing potential and not willing to use a double method of contraception up to 3 months after the end of study treatment. Male patient who is not willing to use a barrier method of contraception up to 3 months after the end of study treatment.
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Panobinostat + Bortezomib + Dexamethasone
干预措施: Panobinostat (Drug)
Panobinostat + Bortezomib + Dexamethasone
干预措施: Bortezomib (Drug)
Panobinostat + Bortezomib + Dexamethasone
干预措施: Dexamethasone (Drug)
Placebo + Bortezomib + Dexamethasone
干预措施: Bortezomib (Drug)
Placebo + Bortezomib + Dexamethasone
干预措施: Dexamethasone (Drug)
Placebo + Bortezomib + Dexamethasone
干预措施: Placebo (Drug)
结局指标
主要结局
Progression Free Survival in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone.
时间窗: 45 months
Progression-free Survival Events in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone.
时间窗: 45 months
次要结局
- Time to Response Per Investigator Assessment (mEBMT Criteria) of Response Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone.(45 months)
- Overall Survival in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone(45 months)
- Overall Response Rate in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone.(45 months)
- Duration of Response Per Investigator Assessment (mEBMT Criteria) Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone.(45 months)
- Time to Progression/Relapse Per Investigator Assessment (mEBMT Criteria) Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone.(45 months)
- European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group(12, 24 and 48 weeks)
- European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC) QLQ-MY20-Change From Baseline by Treatment Group(12, 24 and 48 weeks)
- Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System : FACT/GOG-NTX-Change From Baseline by Treatment Group(12, 24 and 48 weeks)