NCT03319667进行中（未招募）3 期
A Phase 3 Randomized, Open-label, Multicenter Study Assessing the Clinical Benefit of Isatuximab (SAR650984) in Combination With Bortezomib (Velcade®), Lenalidomide and Dexamethasone Versus Bortezomib, Lenalidomide and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Not Eligible for Transplant
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Sanofi
- 入组人数
- 475
- 试验地点
- 199
- 主要终点
- Progression free survival (PFS)
研究概览
简要总结
Primary Objective:
-To demonstrate the benefit of isatuximab in combination with bortezomib, lenalidomide, and dexamethasone in the prolongation of progression free survival (PFS) as compared to bortezomib, lenalidomide, and dexamethasone, in participants with newly diagnosed multiple myeloma (NDMM) not eligible for transplant.
Secondary Objectives:
- To evaluate in both randomized (isatuximab, bortezomib, lenalidomide and dexamethasone combination (IVRd) and bortezomib, lenalidomide and dexamethasone combination (VRd)) arms:
- Complete response (CR) rate, as defined by the International Myeloma Working Group (IMWG) criteria.
- Minimal residual disease (MRD) negativity rate in participants with CR.
- Very good partial response or better rate, as defined by the IMWG criteria.
- Overall survival (OS).
- To evaluate the overall response rate (ORR) as per IMWG criteria.
- To evaluate the time to progression (TTP) overall and by MRD status.
- To evaluate PFS by MRD status.
- To evaluate the duration of response (DOR) overall and by MRD status.
- To evaluate time to first response (TT1R).
- To evaluate time to best response (TTBR).
- To evaluate progression-free survival on next line of therapy (PFS2).
- To evaluate the sustained MRD negativity >12 months rate.
- To evaluate safety.
- To determine the pharmacokinetic (PK) profile of isatuximab in combination with bortezomib, lenalidomide, and dexamethasone (IVRd arm only).
- To evaluate the immunogenicity of isatuximab in participants receiving isatuximab (IVRd and crossover arms).
- To assess disease-specific and generic health-related quality of life (HRQL), disease and treatment-related symptoms, health state utility, and health status.
详细描述
The duration of the study for each participant will include a screening period of up to 4 weeks, an induction period of 24 weeks (4 cycles with a duration of 42 ± 3 days), a continuous treatment period and a crossover period (when applicable). The cycle duration is 28 ± 3 days during the continuous treatment and crossover periods.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inclusion criteria :
- •Multiple myeloma (IMWG criteria).
- •Newly diagnosed multiple myeloma not eligible for transplant due to age (≥ 65 years) or participants < 65 years with comorbidities impacting possibility of transplant.
- •Evidence of measurable disease.
- •Written informed consent.
排除标准
- •Age < 18 years.
- •Prior treatment for multiple myeloma.
- •Any other prior or ongoing disease/health conditions incompatible with the study objectives.
- •Organ function values not met.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status ( PS) >
- •Hypersensitivity to the study medications.
- •Pregnant, breastfeeding, or woman of child bearing potential unwilling to use recommended contraception methods.
- •Male participants who disagree to follow the study contraceptive counseling.
- •The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
研究组 & 干预措施
Isatuximab/Bortezomib/Lenalidomide/Dexamethasone = IVRd arm
Experimental
- Induction treatment with 4x6-week cycles with intravenous (IV) isatuximab + subcutaneous (SC) bortezomib + oral lenalidomide + IV or oral dexamethasone
- Continuous treatment with 4-week cycles with IV isatuximab + oral lenalidomide + IV or oral dexamethasone
干预措施: Isatuximab SAR650984 (Drug)
Isatuximab/Lenalidomide/Dexamethasone = IRd crossover arm
Other
4-weeks cycles with IV isatuximab + oral lenalidomide + IV or oral dexamethasone
干预措施: Isatuximab SAR650984 (Drug)
Isatuximab/Bortezomib/Lenalidomide/Dexamethasone = IVRd arm
Experimental
- Induction treatment with 4x6-week cycles with intravenous (IV) isatuximab + subcutaneous (SC) bortezomib + oral lenalidomide + IV or oral dexamethasone
- Continuous treatment with 4-week cycles with IV isatuximab + oral lenalidomide + IV or oral dexamethasone
干预措施: Bortezomib (Drug)
Isatuximab/Bortezomib/Lenalidomide/Dexamethasone = IVRd arm
Experimental
- Induction treatment with 4x6-week cycles with intravenous (IV) isatuximab + subcutaneous (SC) bortezomib + oral lenalidomide + IV or oral dexamethasone
- Continuous treatment with 4-week cycles with IV isatuximab + oral lenalidomide + IV or oral dexamethasone
干预措施: Lenalidomide (Drug)
Isatuximab/Bortezomib/Lenalidomide/Dexamethasone = IVRd arm
Experimental
- Induction treatment with 4x6-week cycles with intravenous (IV) isatuximab + subcutaneous (SC) bortezomib + oral lenalidomide + IV or oral dexamethasone
- Continuous treatment with 4-week cycles with IV isatuximab + oral lenalidomide + IV or oral dexamethasone
干预措施: Dexamethasone (Drug)
Bortezomib/Lenalidomide/Dexamethasone = VRd arm
Active Comparator
- Induction treatment with 4x6-week cycles with SC bortezomib + oral lenalidomide + IV or oral dexamethasone
- Continuous treatment with 4-week cycles with oral lenalidomide + IV or oral dexamethasone
干预措施: Bortezomib (Drug)
Bortezomib/Lenalidomide/Dexamethasone = VRd arm
Active Comparator
- Induction treatment with 4x6-week cycles with SC bortezomib + oral lenalidomide + IV or oral dexamethasone
- Continuous treatment with 4-week cycles with oral lenalidomide + IV or oral dexamethasone
干预措施: Dexamethasone (Drug)
Bortezomib/Lenalidomide/Dexamethasone = VRd arm
Active Comparator
- Induction treatment with 4x6-week cycles with SC bortezomib + oral lenalidomide + IV or oral dexamethasone
- Continuous treatment with 4-week cycles with oral lenalidomide + IV or oral dexamethasone
干预措施: Lenalidomide (Drug)
Isatuximab/Lenalidomide/Dexamethasone = IRd crossover arm
Other
4-weeks cycles with IV isatuximab + oral lenalidomide + IV or oral dexamethasone
干预措施: Lenalidomide (Drug)
Isatuximab/Lenalidomide/Dexamethasone = IRd crossover arm
Other
4-weeks cycles with IV isatuximab + oral lenalidomide + IV or oral dexamethasone
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Progression free survival (PFS)
时间窗: Up to approximately 100 months after the First Participant In (FPI)
Defined as the time from the date of randomization to the date of first documentation of progression disease (PD) as determined by the independent review committee (IRC) or the date of death from any cause, whichever occurs first.
次要结局
- Complete response rate (CR)(Up to approximately 100 months after the FPI)
- Minimal residual disease (MRD) negativity rate for participants with CR(Up to approximately 100 months after the FPI)
- Very good partial response (VGPR) or better rate(Up to approximately 100 months after the FPI)
- Overall survival (OS)(Up to approximately 110 months after the FPI)
- Overall response rate (ORR)(Up to approximately 100 months after the FPI assessment)
- Time to progression (TTP)(Up to approximately 100 months after FPI)
- Duration of response (DOR)(Up to approximately 100 months after the FPI)
- Time to first response (TT1R)(Up to approximately 100 months after the FPI)
- Time to best response (TTBR)(Up to approximately 100 months after the FPI)
- PFS on next line of therapy (PFS2)(Up to approximately 110 months after the FPI)
- PFS in MRD negative participants(Up to approximately 100 months after the FPI)
- Sustained MRD negativity ≥12 months rate(Up to approximately 100 months after the FPI)
- Adverse Events(Up to 30 days after end of treatment (EOT) visit)
- Assessment of PK parameter: Ctrough(Cycle 1 Day 8/Day 15/Day 29 (pre-dose) and Day 1 (pre-dose) of Cycle 2, 3, 4, 5, 6, 7, 8, 9 and 10 (Duration of each cycle for Cycles 1-4: 6 weeks; Duration of each cycle for Cycles 5-10: 4 weeks))
- Immunogenicity(Up to approximately 100 months after the FPI)
- participants reported outcome (PRO): QLQ-C30(Up to approximately 100 months after the FPI)
- PRO: QLQ-MY20(Up to approximately 100 months after the FPI)
- PRO: EQ-5D-5L(Up to approximately 100 months after the FPI)
研究者
研究点 (199)
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相关资讯
Isatuximab-Based Therapy Shows Sustained Efficacy Across Age Groups in Transplant-Ineligible Multiple Myeloma- Long-term data from the BENEFIT trial demonstrates that isatuximab plus lenalidomide, dexamethasone, and bortezomib (Isa-VRd) achieves significantly higher sustained minimal residual disease negativity rates compared to Isa-Rd in transplant-ineligible newly diagnosed multiple myeloma patients.
- A pooled analysis of 336 patients from the IMROZ study confirms that Isa-VRd maintains consistent efficacy across age groups, with overall response rates exceeding 92% in both patients under and over 75 years of age.
- The treatment regimen shows robust performance in challenging patient populations, including frail patients, though slightly reduced response rates and higher adverse event rates are observed in this subgroup.
- These findings support Isa-VRd as a new standard of care for transplant-ineligible newly diagnosed multiple myeloma patients, providing an important frontline treatment option for elderly and high-risk populations.9 months agoIsatuximab Combinations Show Promise in Newly Diagnosed Multiple Myeloma- Isatuximab plus VRd significantly reduced disease progression or death risk by 40.4% in transplant-ineligible newly diagnosed multiple myeloma patients.
- The FDA approved isatuximab-irfc with VRd for transplant-ineligible multiple myeloma, based on the IMROZ trial data.
- Isatuximab-RVd induction therapy improved progression-free survival in transplant-eligible newly diagnosed multiple myeloma patients, GMMG-HD7 trial showed.
- The addition of isatuximab to RVd led to higher rates of minimal residual disease negativity, indicating deeper responses.last yearMRD Negativity Emerges as Key Endpoint in Multiple Myeloma Trials- Minimal Residual Disease (MRD) testing offers a sensitive method for detecting remaining cancer cells, influencing treatment decisions and improving patient outcomes in multiple myeloma.
- The FDA's ODAC is considering MRD as a surrogate endpoint for drug approval, signaling a shift towards MRD negativity as a primary goal in clinical trials.
- Studies like CEPHEUS, with MRD negativity as the primary endpoint, highlight the increasing importance of achieving and sustaining MRD negativity for better progression-free survival.
- Sustained MRD negativity, particularly for 12 months or longer, significantly reduces the risk of disease progression or death in newly diagnosed multiple myeloma patients.last yearFDA Approvals and Designations in Oncology: September 2024- The FDA approved a subcutaneous formulation of atezolizumab (Tecentriq Hybreza) for various cancers, offering a more convenient administration option for patients.
- Ribociclib (Kisqali) gained approval for early-stage breast cancer, expanding treatment options for this disease and showing improved invasive disease-free survival.
- Pembrolizumab (Keytruda) in combination with chemotherapy was approved for unresectable advanced or metastatic malignant pleural mesothelioma, improving overall survival.
- Isatuximab (Sarclisa) plus bortezomib, lenalidomide, and dexamethasone was approved for transplant-ineligible, newly diagnosed multiple myeloma patients.last year