An Open-Label, Non-Comparative, Two-Cohort, Multicenter Study to Evaluate the Effectiveness and Safety of Ixazomib (NINLARO®) in Combination With Pomalidomide and Dexamethasone (IPd, Cohort A) or With Lenalidomide and Dexamethasone (IRd, Cohort B) in Patients With Relapsed/Refractory Multiple Myeloma Previously Receiving a Parenteral Proteasome Inhibitor-based Treatment Regimen (US MM-7)
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 发起方
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
The main aim is to show that long-term use of ixazomib can improve symptoms of multiple myeloma and provide an effective long-term alternative treatment.
Participants will take ixazomib orally (by mouth) with pomalidomide and dexamethasone or lenalidomide and dexamethasone in 28-day treatment cycles. Participants will be treated for a maximum of 39 cycles but may continue to receive ixazomib beyond 39 cycles if they are benefiting from it. A follow-up study visit will occur 30 days after the last dose of ixazomib. Participants will be monitored for up to 3 years.
详细描述
The main objective is to determine whether an in-class transition (iCT) from a parenteral proteasome inhibitor (PI) regimen to an all-oral ixazomib(NINLARO) regimen can improve outcomes and provide an effective long-term alternative treatment for participants with relapsed and/or refractory multiple myeloma.
The drug being tested in this study is called ixazomib (NINLARO). Ixazomib is being tested to treat people who have relapsed and/or refractory multiple myeloma (R/R MM). This study will look at the efficacy and safety of ixazomib in participants with R/R MM who were previously receiving parenteral proteasome inhibitor (PI)-based therapy in combination with pomalidomide or with lenalidomide, and who undergo in-class transition to an oral ixazomib-based combination containing either pomalidomide (cohort A) or lenalidomide (cohort B).
The study will enroll approximately 140 patients. Participants will be enrolled to one of the two treatment groups, depending on whether they are transitioning from a pomalidomide- or lenalidomide- based regimen:
- Cohort A: Ixazomib 4 mg + Pomalidomide 4 mg + Dexamethasone 40 mg
- Cohort B: Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg
Participants who are >75 years of age at time of enrollment will be instructed to take 20 mg dexamethasone. For participants with moderate or severe hepatic impairment, severe renal impairment, or end-stage renal disease requiring dialysis, the recommended starting dose of ixazomib is 3 mg which can be further reduced to 2.3 mg at investigator's discretion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Cohort A: Ixazomib 4 mg + Pomalidomide 4 mg + Dexamethasone 40 mg
Ixazomib 4 mg (3 mg for participants with moderate or severe hepatic impairment, severe renal impairment, or end-stage renal disease requiring dialysis), capsules, orally, on Days 1, 8, and 15, along with pomalidomide 4 mg, capsules, orally from Days 1 to 21 and dexamethasone 40 mg (20 mg if the participant is over 75 years of age), tablets, orally on Days 1, 8, 15, and 22 of each 28-day cycle, for a maximum of 39 cycles or until disease progression or unacceptable toxicity leading to discontinuation of ixazomib or to a change in regimen. Participants who were taking modified doses of pomalidomide or dexamethasone can start at that dose level in the study.
干预措施: Ixazomib (Drug)
Cohort A: Ixazomib 4 mg + Pomalidomide 4 mg + Dexamethasone 40 mg
Ixazomib 4 mg (3 mg for participants with moderate or severe hepatic impairment, severe renal impairment, or end-stage renal disease requiring dialysis), capsules, orally, on Days 1, 8, and 15, along with pomalidomide 4 mg, capsules, orally from Days 1 to 21 and dexamethasone 40 mg (20 mg if the participant is over 75 years of age), tablets, orally on Days 1, 8, 15, and 22 of each 28-day cycle, for a maximum of 39 cycles or until disease progression or unacceptable toxicity leading to discontinuation of ixazomib or to a change in regimen. Participants who were taking modified doses of pomalidomide or dexamethasone can start at that dose level in the study.
干预措施: Pomalidomide (Drug)
Cohort A: Ixazomib 4 mg + Pomalidomide 4 mg + Dexamethasone 40 mg
Ixazomib 4 mg (3 mg for participants with moderate or severe hepatic impairment, severe renal impairment, or end-stage renal disease requiring dialysis), capsules, orally, on Days 1, 8, and 15, along with pomalidomide 4 mg, capsules, orally from Days 1 to 21 and dexamethasone 40 mg (20 mg if the participant is over 75 years of age), tablets, orally on Days 1, 8, 15, and 22 of each 28-day cycle, for a maximum of 39 cycles or until disease progression or unacceptable toxicity leading to discontinuation of ixazomib or to a change in regimen. Participants who were taking modified doses of pomalidomide or dexamethasone can start at that dose level in the study.
干预措施: Dexamethasone (Drug)
Cohort B: Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg
Ixazomib 4 mg (3 mg for participants with moderate or severe hepatic impairment, severe renal impairment, or end-stage renal disease requiring dialysis), capsules, orally, on Days 1, 8, and 15, along with lenalidomide 25 mg capsules, orally, from Days 1 to 21 and dexamethasone 40 mg (20 mg if the participant is over 75 years of age), tablets, orally, on Days 1, 8, 15, and 22 of each 28-day cycle, for a maximum of 39 cycles or until disease progression or unacceptable toxicity leading to discontinuation of ixazomib or to a change in regimen. Participants who were taking modified doses of lenalidomide or dexamethasone can start at that dose level in the study.
干预措施: Ixazomib (Drug)
Cohort B: Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg
Ixazomib 4 mg (3 mg for participants with moderate or severe hepatic impairment, severe renal impairment, or end-stage renal disease requiring dialysis), capsules, orally, on Days 1, 8, and 15, along with lenalidomide 25 mg capsules, orally, from Days 1 to 21 and dexamethasone 40 mg (20 mg if the participant is over 75 years of age), tablets, orally, on Days 1, 8, 15, and 22 of each 28-day cycle, for a maximum of 39 cycles or until disease progression or unacceptable toxicity leading to discontinuation of ixazomib or to a change in regimen. Participants who were taking modified doses of lenalidomide or dexamethasone can start at that dose level in the study.
干预措施: Lenalidomide (Drug)
Cohort B: Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg
Ixazomib 4 mg (3 mg for participants with moderate or severe hepatic impairment, severe renal impairment, or end-stage renal disease requiring dialysis), capsules, orally, on Days 1, 8, and 15, along with lenalidomide 25 mg capsules, orally, from Days 1 to 21 and dexamethasone 40 mg (20 mg if the participant is over 75 years of age), tablets, orally, on Days 1, 8, 15, and 22 of each 28-day cycle, for a maximum of 39 cycles or until disease progression or unacceptable toxicity leading to discontinuation of ixazomib or to a change in regimen. Participants who were taking modified doses of lenalidomide or dexamethasone can start at that dose level in the study.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: Up to approximately 5 years
PFS is defined as the time from the date of the first administration of the study drug regimen ixazomib with pomalidomide and dexamethasone or ixazomib with lenalidomide and dexamethasone (IPd/IRd) to the date of the first documentation of disease progression before the start of next line of therapy based on local laboratory results and the investigator's assessment using modified International Myeloma Working Group (IMWG) response criteria or death due to any cause, whichever occurs first.
次要结局
- Duration of Therapy (DoT 2)(Up to approximately 5 years)
- Duration of PI Therapy(Up to approximately 5 years)
- Percentage of Participants Maintaining or Achieving PR, Very Good Partial Response (VGPR), or Complete Response (CR)(Up to approximately 5 years)
- Time to Progression (TTP)(Up to approximately 5 years)
- Duration of Therapy (DoT 1)(Up to approximately 5 years)
- Duration of Ixazomib Therapy(Up to approximately 5 years)
- Relative Dose Intensity (RDI) for Each Drug in the Treatment Regimen(Up to approximately 5 years)
- Percentage of Participants who Experience at Least One Treatment Emergent Adverse Event (TEAE)(Up to approximately 5 years)