A Phase 2, Open-Label, Multi-Center Study of Venetoclax in Combination With Carfilzomib and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 120
- 试验地点
- 32
- 主要终点
- Objective Response Rate (ORR) of VenKd in Participants with Relapsed or Refractory Multiple Myeloma (RRMM) as well as Those with t(11;14)-positive RRMM
研究概览
简要总结
A Phase 2, open-label, dose escalation study to evaluate the safety and efficacy of venetoclax in combination with carfilzomib-dexamethasone (Kd) in participants with relapsed or refractory MM and have received 1 to 3 prior lines of therapy.
Part 4 of this study is currently enrolling.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Eastern Collaborative Oncology Group (ECOG) performance score of less than or equal to
- •Documented relapsed or progressive Multiple Myeloma (MM) on or after any regimen or is refractory to the most recent line of therapy.
- •Positive for translocation t(11;14) as determined by an analytically validated Fluorescent In Situ Hybridization (FISH) assay per central laboratory testing.
- •Received prior treatment with at least 1 prior line of therapy for MM.
- •Measurable disease on Screening per International Myeloma Working Group (IMWG) criteria.
- •Meets absolute neutrophil count, platelet count, hemoglobin, liver and kidney function laboratory values within 2 weeks prior to first dose of study drug.
排除标准
- •Has a pre-existing condition that is contraindicated including.
- •Non-secretory or oligo-secretory MM
- •Active plasma cell leukemia.
- •Waldenström's macroglobulinemia.
- •Primary amyloidosis.
- •POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
- •Active hepatitis B or C infection based on screening blood testing.
- •Known active Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
- •Significant cardiovascular disease.
- •Major surgery within 4 weeks prior to first dose.
- •Acute infections requiring antibiotic, antifungal or antiviral therapy within14 days prior to first dose.
- •Peripheral neuropathy ≥ Grade 3 or ≥ Grade 2 with pain within 2 weeks prior to first dose.
- •Uncontrolled diabetes or uncontrolled hypertension within 14 days prior to first dose.
- •Any other medical condition that, in the opinion of the Investigator, would adversely affect the participant's participation in the study.
- •History of other active malignancies, including myelodysplastic syndrome (MDS), within the past 3 years prior to study entry Other protocol defined inclusion/exclusion criteria could apply
研究组 & 干预措施
Venetoclax + Carfilzomib + Dexamethasone
Part 1: Evaluate the safety and pharmacokinetic profiles while providing information to determine the appropriate doses of venetoclax and carfilzomib (VenKd) to be used in the VenKd combination in approximately 18 participants. The dose levels are Venetoclax 400 mg or 800 mg; Carfilzomib 20/27 mg/m2, 20/70 mg/m2, and/or 20/56 mg/m2; Dexamethasone 40 mg
Part 2: Further evaluate the safety and efficacy profile of the VenKd combination selected after completion of Part 1 in approximately 22 additional participants. Participants may discontinue Kd but may continue receiving venetoclax once daily (QD) as monotherapy.
Part 3: Further evaluation of the efficacy of the VenKd combination after completion of Part 1 and Part 2 in 7 additional participants.
Part 4, An additional 65 participants t(11;14) positive will receive varying doses of the VenKd combination or carfilzomib and dexamethasone
干预措施: Carfilzomib (Drug)
Venetoclax + Carfilzomib + Dexamethasone
Part 1: Evaluate the safety and pharmacokinetic profiles while providing information to determine the appropriate doses of venetoclax and carfilzomib (VenKd) to be used in the VenKd combination in approximately 18 participants. The dose levels are Venetoclax 400 mg or 800 mg; Carfilzomib 20/27 mg/m2, 20/70 mg/m2, and/or 20/56 mg/m2; Dexamethasone 40 mg
Part 2: Further evaluate the safety and efficacy profile of the VenKd combination selected after completion of Part 1 in approximately 22 additional participants. Participants may discontinue Kd but may continue receiving venetoclax once daily (QD) as monotherapy.
Part 3: Further evaluation of the efficacy of the VenKd combination after completion of Part 1 and Part 2 in 7 additional participants.
Part 4, An additional 65 participants t(11;14) positive will receive varying doses of the VenKd combination or carfilzomib and dexamethasone
干预措施: Venetoclax (Drug)
Venetoclax + Carfilzomib + Dexamethasone
Part 1: Evaluate the safety and pharmacokinetic profiles while providing information to determine the appropriate doses of venetoclax and carfilzomib (VenKd) to be used in the VenKd combination in approximately 18 participants. The dose levels are Venetoclax 400 mg or 800 mg; Carfilzomib 20/27 mg/m2, 20/70 mg/m2, and/or 20/56 mg/m2; Dexamethasone 40 mg
Part 2: Further evaluate the safety and efficacy profile of the VenKd combination selected after completion of Part 1 in approximately 22 additional participants. Participants may discontinue Kd but may continue receiving venetoclax once daily (QD) as monotherapy.
Part 3: Further evaluation of the efficacy of the VenKd combination after completion of Part 1 and Part 2 in 7 additional participants.
Part 4, An additional 65 participants t(11;14) positive will receive varying doses of the VenKd combination or carfilzomib and dexamethasone
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Objective Response Rate (ORR) of VenKd in Participants with Relapsed or Refractory Multiple Myeloma (RRMM) as well as Those with t(11;14)-positive RRMM
时间窗: First dose of study drug through at least 30 days after end of treatment (approximately 2 years)
ORR is defined as the percentage of participants with a documented PR or better based on IMWG criteria.
Number of Participants with Adverse Events
时间窗: First dose of study drug through at least 30 days after end of treatment (approximately 2 years)
An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
Very Good Partial Response (VGPR) or Better Response Rate of VenKd in Participants with Relapsed or Refractory Multiple Myeloma (RRMM) as well as Those with t(11;14)-positive RRMM
时间窗: First dose of study drug through at least 30 days after end of treatment (approximately 2 years)
VGPR or better response rate is defined as the percentage of participants with documented VGPR or better based on IMWG criteria.
Complete Response (CR) or Better Rate of VenKd in Participants with Relapsed or Refractory Multiple Myeloma (RRMM) as well as Those with t(11;14)-positive RRMM
时间窗: First dose of study drug through at least 30 days after end of treatment (approximately 2 years)
Complete response or better rate is defined as the percentage of participants with documented CR or better based on IMWG criteria.
次要结局
- Cmax of Carfilzomib(Approximately 4 hours post-dose on Cycle 1 Days 1 and 15)
- Very Good Partial Response (VGPR) or Better Response Rate in Participants with Relapsed or Refractory Multiple Myeloma and in a Subset of Participants with High B-cell lymphocyte-2 (BCL-2) Expression(Up to approximately 17 months)
- Clearance (CL) of Carfilzomib(Approximately 4 hours post-dose on Cycle 1 Days 1 and 15)
- Progression-free survival (PFS) in Participants with Relapsed or Refractory Multiple Myeloma and in a Subset of Participants with High B-cell lymphocyte-2 (BCL-2) Expression(Up to approximately 17 months)
- Minimal residual disease (MRD)(Up to 2 years (Screening, Cycle 3 Day 1, and Confirmation of Stringent Complete Response [sCR]/Complete Response [CR]))
- Duration of Overall Response (DOR) in Participants with Relapsed or Refractory Multiple Myeloma and in a Subset of Participants with High B-cell lymphocyte-2 (BCL-2) Expression(Up to approximately 17 months)
- Terminal Phase Elimination Rate Constant (β) of Carfilzomib(Approximately 4 hours post-dose on Cycle 1 Days 1 and 15)
- AUC from 0 to Infinity (AUC∞) of Carfilzomib(Approximately 4 hours post-dose on Cycle 1 Days 1 and 15)
- AUC from Time 0 to the Time of the Last Measurable Concentration (AUCt) of Carfilzomib(Approximately 4 hours post-dose on Cycle 1 Days 1 and 15)
- Maximum Plasma Concentration (Cmax) of Venetoclax(Approximately 24 hours post-dose on Cycle 1 Days 1 and 15)
- Time to progression (TTP) in Participants with Relapsed or Refractory Multiple Myeloma and in a Subset of Participants with High B-cell lymphocyte-2 (BCL-2) Expression(Up to approximately 17 months)
- Objective response rate (ORR) in Participants with Relapsed or Refractory Multiple Myeloma and in a Subset of Participants with High B-cell lymphocyte-2 (BCL-2) Expression(Up to approximately 17 months)
- Time to Response (TTR) in Participants with Relapsed or Refractory Multiple Myeloma and in a Subset of Participants with High B-cell lymphocyte-2 (BCL-2) Expression(Up to approximately 17 months)
- Area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) post-dose of Venetoclax(Approximately 24 hours post-dose on Cycle 1 Days 1 and 15)
- Terminal Elimination Half-life (t1/2) of Carfilzomib(Approximately 4 hours post-dose on Cycle 1 Days 1 and 15)
- Time to Maximum Plasma Concentration (Peak Time, Tmax) of Venetoclax(Approximately 24 hours post-dose on Cycle 1 Days 1 and 15)