A Phase 3 Randomized, Open-label, Multicenter Study of Isatuximab (SAR650984) in Combination With Lenalidomide and Dexamethasone Versus Lenalidomide and Dexamethasone in Patients With High-risk Smoldering Multiple Myeloma
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Sanofi
- 入组人数
- 337
- 试验地点
- 105
- 主要终点
- Number of participants with Treatment-emergent adverse events (AEs) and serious adverse events- Safety Run-in Part
研究概览
简要总结
Primary Objectives:
- Safety run-in Part: To confirm the recommended dose of isatuximab when combined with lenalidomide and dexamethasone in participants with high-risk smoldering multiple myeloma (SMM)
- Randomized Phase 3 Part: To demonstrate the clinical benefit of isatuximab in combination with lenalidomide and dexamethasone in the prolongation of progression-free survival when compared to lenalidomide and dexamethasone in subjects with high-risk SMM
Secondary Objectives:
Safety run-in Part:
- To assess overall response rate (ORR)
- To assess duration of response (DOR)
- To assess minimal residual disease (MRD) negativity in participants achieving very good partial response (VGPR) or complete response (CR)
- To assess time to diagnostic (SLiM CRAB) progression or death
- To assess time to first-line treatment for multiple myeloma (MM)
- To assess the potential immunogenicity of isatuximab
- Impact of abnormal chromosomal subtype on participant outcome
Randomized Phase 3 Part:
Key Secondary Objectives:
To compare between the arms
- MRD negativity
- Sustained MRD negativity
- Second progression-free survival (PFS2)
- Overall survival
Other Secondary Objectives:
To evaluate in both arms
- CR rate
- ORR
- DOR
- Time to diagnostic (SLiM CRAB) progression
- Time to biochemical progression
- Time to first-line treatment for MM
- Impact of abnormal chromosomal subtype on participant outcome
- Safety and tolerability
- Pharmacokinetics (PK)
- Potential of isatuximab immunogenicity
- Clinical outcome assessments (COAs)
详细描述
Study duration is expected to be approximately 12 years, including a 42-day screening period, followed by an up to 36-month treatment period, and a follow-up period of approximately 9 years.
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 (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Isatuximab, lenalidomide, and dexamethasone (ILd)
Participants will receive isatuximab [intravenous (IV) administration] in combination with lenalidomide [per os (PO) administration] and dexamethasone [IV on Day 1 of Cycle 1 for participants receiving isatuximab IV only and PO otherwise for subsequent cycles] for 24 cycles followed by isatuximab monotherapy for 12 cycles for a total duration of 36 cycles. 1 cycle = 28 days. Participants may receive other treatments as pre-medication.
干预措施: Isatuximab SAR650984 (Drug)
Isatuximab, lenalidomide, and dexamethasone (ILd)
Participants will receive isatuximab [intravenous (IV) administration] in combination with lenalidomide [per os (PO) administration] and dexamethasone [IV on Day 1 of Cycle 1 for participants receiving isatuximab IV only and PO otherwise for subsequent cycles] for 24 cycles followed by isatuximab monotherapy for 12 cycles for a total duration of 36 cycles. 1 cycle = 28 days. Participants may receive other treatments as pre-medication.
干预措施: Lenalidomide (Drug)
Isatuximab, lenalidomide, and dexamethasone (ILd)
Participants will receive isatuximab [intravenous (IV) administration] in combination with lenalidomide [per os (PO) administration] and dexamethasone [IV on Day 1 of Cycle 1 for participants receiving isatuximab IV only and PO otherwise for subsequent cycles] for 24 cycles followed by isatuximab monotherapy for 12 cycles for a total duration of 36 cycles. 1 cycle = 28 days. Participants may receive other treatments as pre-medication.
干预措施: Dexamethasone (Drug)
Isatuximab, lenalidomide, and dexamethasone (ILd)
Participants will receive isatuximab [intravenous (IV) administration] in combination with lenalidomide [per os (PO) administration] and dexamethasone [IV on Day 1 of Cycle 1 for participants receiving isatuximab IV only and PO otherwise for subsequent cycles] for 24 cycles followed by isatuximab monotherapy for 12 cycles for a total duration of 36 cycles. 1 cycle = 28 days. Participants may receive other treatments as pre-medication.
干预措施: Montelukast or equivalent (Drug)
Isatuximab, lenalidomide, and dexamethasone (ILd)
Participants will receive isatuximab [intravenous (IV) administration] in combination with lenalidomide [per os (PO) administration] and dexamethasone [IV on Day 1 of Cycle 1 for participants receiving isatuximab IV only and PO otherwise for subsequent cycles] for 24 cycles followed by isatuximab monotherapy for 12 cycles for a total duration of 36 cycles. 1 cycle = 28 days. Participants may receive other treatments as pre-medication.
干预措施: Acetaminophen (Drug)
Isatuximab, lenalidomide, and dexamethasone (ILd)
Participants will receive isatuximab [intravenous (IV) administration] in combination with lenalidomide [per os (PO) administration] and dexamethasone [IV on Day 1 of Cycle 1 for participants receiving isatuximab IV only and PO otherwise for subsequent cycles] for 24 cycles followed by isatuximab monotherapy for 12 cycles for a total duration of 36 cycles. 1 cycle = 28 days. Participants may receive other treatments as pre-medication.
干预措施: Diphenhydramine or equivalent (Drug)
Isatuximab, lenalidomide, and dexamethasone (ILd)
Participants will receive isatuximab [intravenous (IV) administration] in combination with lenalidomide [per os (PO) administration] and dexamethasone [IV on Day 1 of Cycle 1 for participants receiving isatuximab IV only and PO otherwise for subsequent cycles] for 24 cycles followed by isatuximab monotherapy for 12 cycles for a total duration of 36 cycles. 1 cycle = 28 days. Participants may receive other treatments as pre-medication.
干预措施: Methylprednisolone or equivalent (Drug)
Lenalidomide and dexamethasone (Ld)
Lenalidomide [PO administration] in combination with dexamethasone [PO administration] for 24 cycles. 1 cycle = 28 days
干预措施: Lenalidomide (Drug)
Lenalidomide and dexamethasone (Ld)
Lenalidomide [PO administration] in combination with dexamethasone [PO administration] for 24 cycles. 1 cycle = 28 days
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Number of participants with Treatment-emergent adverse events (AEs) and serious adverse events- Safety Run-in Part
时间窗: Up to approximately 63 months
Plasma concentration of isatuximab during the treatment period - Safety Run-in Part
时间窗: After first infusion from Cycle 1 Day 1 to Day 28 in safety run-in part
Receptor density/receptor occupancy Safety Run-in Part
时间窗: Baseline to Cycle 2 Day 1 (each cycle is 28 days)
Change in CD38 receptor occupancy from baseline
Progression-free survival (PFS) Randomized Phase 3 Part
时间窗: Up to approximately 114 months
PFS defined as the time from randomization to MM (SLiM CRAB criteria) or other related conditions based on independent review committee (IRC) assessment according to 2014 International Myeloma Working Group (IMWG) criteria or death from any cause, whichever happens first
次要结局
- Concentration observed at the end of intravenous infusion.(Ceoi)- Safety Run-in Part(Day 1 of Cycle 1 to 4)
- Overall Response Rate (ORR)- Safety Run-in Part(Up to approximately 63 months)
- Duration of Response (DOR) - Safety Run-in Part(Up to approximately 63 months)
- Minimal residual disease (MRD) negativity -Safety Run-in Part(Up to approximately 36 months)
- Time to diagnostic (SLiM CRAB) progression or death - Safety Run-in Part(Up to approximately 63 months)
- Time to first-line treatment for multiple myeloma (MM) - Safety Run-in Part(Up to approximately 63 months)
- Number of participants with anti-drug antibodies (ADA) against isatuximab- Safety Run-in Part(Up to approximately 63 months)
- PFS in participants with chromosomal abnormalities - Safety Run-In Part(Up to approximately 63 months)
- Overall Survival (OS) in participants with chromosomal abnormalities - Safety Run-In Part(Up to approximately 63 months)
- Minimal residual disease (MRD) negativity - Randomized Phase 3 Part(Up to approximately 36 months)
- Sustained MRD negativity - Randomized Phase 3 Part(Up to approximately 36 months)
- Second PFS (PFS2) - Randomized Phase 3 Part(Up to approximately 144 months)
- OS - Randomized Phase 3 Part(Up to approximately 114 months)
- Complete response (CR) rate - Randomized Phase 3 Part(Up to approximately 114 months)
- Overall Response Rate (ORR) - Randomized Phase 3 Part(Up to approximately 114 months)
- Duration of response (DOR) - Randomized Phase 3 Part(Up to approximately 114 months)
- Time to diagnostic (SLiM CRAB) progression - Randomized Phase 3 Part(Up to approximately 114 months)
- Time to biochemical progression - Randomized Phase 3 Part(Up to approximately 114 months)
- Time to first-line treatment for MM- Randomized Phase 3 Part(Up to approximately 144 months)
- PFS in participants with chromosomal abnormalities - Randomized Phase 3 Part(Up to approximately 114 months)
- OS in participants with chromosomal abnormalities - Randomized Phase 3 Part(Up to approximately 144 months)
- Number of participants with Treatment-emergent adverse events (AEs) and serious adverse events - Randomized Phase 3 Part(Up to approximately 144 months)
- Plasma concentration of isatuximab (Ctrough)- Safety Run-in and Randomized Phase 3 Part(Baseline to Cycle 2 Day 1 (each cycle is 28 days))
- Number of participants with Incidence of anti-drug antibodies (ADA) against isatuximab- Randomized Phase 3 Part(Up to approximately 144 months)
- European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 - Randomized Phase 3 Part(Baseline to follow-up (up to approximately 114 months))
- EORTC QLQ-MY20 - Randomized Phase 3 Part(Baseline to follow-up (up to approximately 114 months))
- EQ-5D-5L - Randomized Phase 3 Part(Baseline to follow-up (up to approximately 114 months))
- Randomized Phase 3: HRUPQ - Randomized Phase 3 Part(Baseline to follow-up (up to approximately 114 months))
- Patient's Qualitative Assessment of Treatment Version 2 (PQAT-v2) - Randomized Phase 3 Part(End of treatment (up to approximately 3 year))