A Randomized, Triple-arm, Controlled, Open-label, Multicenter Phase II Study Assessing Two Different Doses of Panobinostat in Combination With Carfilzomib and Dexamethasone in Relapsed or Relapsed and Refractory Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Overall response rate (ORR) using investigator's response assessment
研究概览
简要总结
The purpose of this study is to investigate the anti-myeloma effect of panobinostat given at two different doses (10 mg and 20 mg oral) in combination with carfilzomib (20/56 mg/m2 i.v.) and low dose dexamethasone (20 mg oral) vs carfilzomib plus low-dose dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma. Safety and efficacy will be evaluated. Treatment will be administered in 4-week cycles until patients discontinue due to disease progression or unacceptable toxicity or for other reasons.
Patients who discontinue the study treatment for reasons other than documented disease progression will be followed for disease assessments every 8 weeks until progression. All patients will be followed for survival until 3 years have passed from their entry into the study, or they have discontinued the follow up earlier.
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
- •Previous diagnosis of MM based on IMWG definitions (Rajkumar, 2014)
- •Prior treatment with 1 to 3 prior lines of therapy
- •Relapsed or relapsed and refractory MM
- •Measureable disease at screening based on central laboratory assessment
- •ECOG Performance status ≤ 2
- •Acceptable lab values prior to starting study treatment
排除标准
- •Primary refractory myeloma
- •Prior treatment with DAC inhibitors including panobinostat
- •Prior treatment with carfilzomib
- •Allogeneic stem cell transplant recipient with graft versus host disease (either active or requiring immunosuppression)
- •Any concomitant anti-cancer therapy besides the study treatment (bisphosphonates are permitted only if commenced prior to the start of screening period)
- •Intolerance to dexamethasone or contraindication to carfilzomib or dexamethasone
- •Unresolved diarrhea ≥ CTCAE grade 2 or a medical condition associated with chronic diarrhea (such as irritable bowel syndrome, inflammatory bowel disease)
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Arm A: PAN (10mg) + CFZ + Dex
Panobinostat (PAN) 10mg orally, combined with carfilzomib (CFZ) 20/56 mg/m2 i.v. and dexamethasone (Dex) 20mg orally, in 4 week cycle
干预措施: panobinostat (capsules) (Drug)
Arm A: PAN (10mg) + CFZ + Dex
Panobinostat (PAN) 10mg orally, combined with carfilzomib (CFZ) 20/56 mg/m2 i.v. and dexamethasone (Dex) 20mg orally, in 4 week cycle
干预措施: carfilzomib (infusion) (Drug)
Arm A: PAN (10mg) + CFZ + Dex
Panobinostat (PAN) 10mg orally, combined with carfilzomib (CFZ) 20/56 mg/m2 i.v. and dexamethasone (Dex) 20mg orally, in 4 week cycle
干预措施: dexamethasone (tablets) (Drug)
Arm B: PAN (20mg) + CFZ + Dex
Panobinostat (PAN) 20mg orally, combined with carfilzomib (CFZ) 20/56 mg/m2 i.v. and dexamethasone (Dex) 20mg orally, in 4 week cycle
干预措施: panobinostat (capsules) (Drug)
Arm B: PAN (20mg) + CFZ + Dex
Panobinostat (PAN) 20mg orally, combined with carfilzomib (CFZ) 20/56 mg/m2 i.v. and dexamethasone (Dex) 20mg orally, in 4 week cycle
干预措施: carfilzomib (infusion) (Drug)
Arm B: PAN (20mg) + CFZ + Dex
Panobinostat (PAN) 20mg orally, combined with carfilzomib (CFZ) 20/56 mg/m2 i.v. and dexamethasone (Dex) 20mg orally, in 4 week cycle
干预措施: dexamethasone (tablets) (Drug)
Arm C: CFZ + Dex
Carfilzomib (CFZ) 20/56 mg/m2 i.v. and dexamethasone (Dex) 20mg orally, in 4 week cycle
干预措施: carfilzomib (infusion) (Drug)
Arm C: CFZ + Dex
Carfilzomib (CFZ) 20/56 mg/m2 i.v. and dexamethasone (Dex) 20mg orally, in 4 week cycle
干预措施: dexamethasone (tablets) (Drug)
结局指标
主要结局
Overall response rate (ORR) using investigator's response assessment
时间窗: All patients treated for 6 cycles (cycle=28 days)
The primary endpoint if Overall Response Rate (ORR) using investigator response assessment according to IMWG criteria. The analysis of ORR will be performed after all randomized patients have completed 6 months of study treatment or discontinued treatment earlier.
次要结局
- Progression-free survival (PFS) using investigator's response assessment based on IMWG criteria(All patients treated for 6 cycles (cycle=28 days))
- Overall survival (OS)(All patients treated for 6 cycles (cycle=28 days))
- Minimum observed plasma concentration (Cmin) for carfilzomib(All patients treated for 6 cycles (cycle=28 days))
- Concentration of panobinostat in blood plasma in 48 hrs after the dose.(All patients treated for 6 cycles (cycle = 28 days))
- Very Good Partial Response (VGPR) or better as best response using investigator response assessment based on International Myeloma Working Group (IMWG) criteria(All patients treated for 6 cycles (cycle=28 days))
- Time to response (TTR) using investigator's response assessment based on IMWG criteria(All patients treated for 6 cycles (cycle=28 days))
- Duration of Response (DOR) using investigator's response assessment based on IMWG criteria(All patients treated for 6 cycles (cycle = 28 days))
- Time to progression (TTP) using investigator's response assessment based on IMWG criteria(All patients treated for 6 cycles (cycle = 28 days))
- Time to reach Cmax for panobinostat (PAN) and carfilzomib (CFZ)(All patients treated for 6 cycles (cycle=28 days);)
- Total carfilzomib exposure over time in blood plasma .(All patients treated for 6 cycles (cycle=28 days))
- Health related quality of life (HRQoL) change over time measured by EORTC questionnaire QLQ-C30 and QLQ-MY20 for disease symptoms(All patients treated for 6 cycles (cycle=28 days))