A Prospective, Randomized, Multi-center Study Comparing Isatuximab in Combination With VRD Versus VRD in High-Risk, Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma.
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 117
- 试验地点
- 1
- 主要终点
- MRD negativity rate at 12 months
研究概览
简要总结
This is a multicenter, prospective, randomized controlled trial designed to compare the quadruplet regimen of isatuximab, bortezomib, lenalidomide, and dexamethasone (Isa-VRD) with the standard triplet regimen (VRD) in newly diagnosed, transplant-ineligible patients with high-risk multiple myeloma (HRMM).
Primary Hypothesis:
The addition of isatuximab to VRD will significantly improve the MRD negativity rate at 12 months compared to VRD alone in HR-NDMM patients.
Secondary Hypotheses:
Isa-VRD will lead to higher overall response rates (ORR), deeper responses, and improved progression-free survival (PFS) and overall survival (OS).
The safety profile of Isa-VRD will be manageable and consistent with the known safety profiles of its individual components.
详细描述
This is a prospective, multicenter, randomized, open-label, Phase IIIb clinical trial. The study aims to evaluate the efficacy and safety of the quadruplet regimen Isatuximab in combination with Bortezomib, Lenalidomide, and Dexamethasone (Isa-VRD) compared to the standard triplet regimen of Bortezomib, Lenalidomide, and Dexamethasone (VRD) in newly diagnosed high-risk multiple myeloma (HRMM) patients who are not candidates for autologous stem cell transplantation.
A total of 117 participants will be enrolled and randomly assigned in a 2:1 ratio to receive either Isa-VRD (78 participants) or VRD (39 participants). The study consists of an induction-consolidation phase (cycles 1-12) followed by a maintenance phase (from cycle 13 onwards until disease progression or unacceptable toxicity).
The primary endpoint is the rate of minimal residual disease (MRD) negativity in the bone marrow assessed by flow cytometry at 12 months of treatment. Key secondary endpoints include MRD negativity rate at 18 months, objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety profile.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Newly diagnosed Multiple myeloma ，meeting the IMWG 2025 definition of high-risk MM (any one criterion):
- •(1) Del(17p) (>20% of plasma cells) and/orTP53 mutation or（2）One of these translocations cooccurring with 1q+ and/or del(1p32) , or t(4;14), or t(14;16), or t(14;20) or （3） Monoallelic del(1p32) along with 1q+ or biallelic del(1p32) or（4） High β2M (>5.5 mg/dL) with normal creatinine (<1.2 mg/dL) or（5）Or presents with any other high-risk feature: meeting diagnostic criteria for primary plasma cell leukemia or presence of extramedullary plasmacytoma at baseline;
- •Age ≥18 years and ≤80 years;
- •Not eligible for autologous hematopoietic stem cell transplantation or has declined transplantation for other reasons.
- •ECOG score 0-2
- •Expected survival time > 3 months
- •Sufficient organ function is defined as follows: absolute neutrophil count ≥ 1.0×10^9/L, platelet count ≥ 50×10^9/L (when the proportion of bone marrow plasma cells is <50%), hemoglobin ≥ 7.5 g/dL; total bilirubin ≤ 1.5 times the upper limit of normal, aspartate aminotransferase and alanine aminotransferase ≤ 2.5 times the upper limit of normal; creatinine clearance rate ≥ 30 mL/min; left ventricular ejection fraction ≥ 50%.
- •Fertile female or male subjects must agree to take effective contraceptive measures during the study period and within the specified time after the last administration.
- •Voluntarily participated in this study, signed the informed consent form, had good compliance, and was cooperative during the follow-up.
排除标准
- •Prior systemic anti-myeloma therapy;
- •Viral infections including HBV, HCV, HIV, etc.;
- •Serious cardiovascular and cerebrovascular diseases, such as: within 6 months before screening, myocardial infarction, unstable angina pectoris, severe arrhythmia, New York Heart Function Classification III-IV grade, or left ventricular ejection fraction <50%.
- •Severe neurological or mental disorders that affect the ability to give informed consent or comply with the protocol.
- •Had an allergic reaction to isatuximab, bortezomib, lenalidomide, dexamethasone or any excipients
- •Pregnant or lactating women.
- •Participated in other interventional clinical studies, or had received other anti-tumor treatments within the specified time before the first administration of this study.
- •The researcher believes that there are any other circumstances unsuitable for participating in this study.
研究组 & 干预措施
IsaVRD group
Participants in this group will receive the quadruplet induction-consolidation regimen of Isatuximab in combination with Bortezomib, Lenalidomide, and Dexamethasone (Isa-VRD) for 12 cycles (each cycle is 28 days). This will be followed by a maintenance therapy with Isatuximab, Bortezomib and Lenalidomide until disease progression or unacceptable toxicity.
干预措施: Isatuximab, bortezomib, lenalidomide, dexamethason (Drug)
VRD group
Participants in this group will receive the standard triplet induction-consolidation regimen of Bortezomib, Lenalidomide, and Dexamethasone (VRD) for 12 cycles (each cycle is 28 days). This will be followed by a maintenance therapy with Bortezomib and Lenalidomide until disease progression or unacceptable toxicity.
干预措施: Bortezomib, Lenalidomide, Dexamethasone (Drug)
结局指标
主要结局
MRD negativity rate at 12 months
时间窗: at 12 months post-treatment initiation
MRD negativity rate at 12 months post-treatment initiation, assessed by EuroFlow (NGF) with a sensitivity of at least 10-5
次要结局
- Progression-free survival(From date of enrollment until the date of first documented progression)
- MRD negativity rate at 18 months(at 18 months post-treatment initiation)
- overall survival(: From date of enrollment until the date of death from any cause)
- Overall response rate(From randomization until the end of the induction-consolidation phase)
研究者
Junling Zhuang
Professor
Peking Union Medical College Hospital