NCT03901963已完成3 期
A Randomized Study of Daratumumab Plus Lenalidomide Versus Lenalidomide Alone as Maintenance Treatment in Patients With Newly Diagnosed Multiple Myeloma Who Are Minimal Residual Disease Positive After Frontline Autologous Stem Cell Transplant
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 200
- 试验地点
- 144
- 主要终点
- Percentage of Participants Who Had Minimal Residual Disease (MRD) Conversion From Baseline to 12 Months After Start of Maintenance Treatment as Determined by Next Generation Sequencing (NGS)
研究概览
简要总结
The purpose of this study is to evaluate conversion rate to minimal residual disease (MRD) negativity following the addition of daratumumab to lenalidomide relative to lenalidomide alone, when administered as maintenance treatment to anti-cluster of differentiation 38 (CD38) treatment naive participants with newly diagnosed multiple myeloma who are MRD positive as determined by next generation sequencing (NGS) at screening, following high-dose therapy (HDT) and autologous stem cell transplant (ASCT).
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 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must have newly diagnosed multiple myeloma with a history of a minimum of 4 cycles of induction therapy, have received high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) within 12 months of the start of induction therapy, and be within 6 months of ASCT on the date of randomization
- •Must have a very good partial response (VGPR) or better response assessed per International Myeloma Working Group (IMWG) 2016 criteria at the time of randomization
- •Must have archived bone marrow samples collected before induction treatment (that is, at diagnosis) or before transplant (for example, at the end of induction) or have existing results on the index multiple myeloma clone based on Adaptive Biotechnologies' next generation sequencing (NGS)-based minimal residual disease (MRD) assay. Archived bone marrow samples will be used for calibration of myeloma clonal cells to facilitate assessment of primary end point by NGS. If an existing result on index myeloma clone is available from Adaptive Biotechnologies' NGS-based MRD assay, as part of institutional procedures, an archived bone marrow sample is not required as long as Adaptive Biotechnologies is able to retrieve historical results on the index myeloma clone form the clinical database. Any one of the following archived samples are required: (a) Greater than 1 milliliter (mL) viable frozen bone marrow aspirated aliquot (preferred) collected in an ethylenediaminetetra-acetic acid (EDTA) tube, frozen, and stored at a temperature of -80 centigrade (°C), or; (b) Non-decalcified diagnostic bone marrow aspirate clot sections (block or slides) for MRD assessment: (i) A formalin fixed paraffin embedded (FFPE) block of bone marrow aspirate clot, or slides (preferably 5, if available), 5 micrometer each, of non-decalcified bone marrow, or; (ii) Slides (preferably 5, if available), bone marrow aspirate smear; (iii) Please note, bone marrow core sections are not acceptable samples for analysis; (iv) In exceptional circumstances when index myeloma clone cannot be identified from the archived bone marrow sample, a post-transplant sample can be used to identify myeloma clone with permission from the sponsor
- •Must have residual disease as defined by detectable MRD (Adaptive Biotechnologies' NGS based MRD assay)
- •Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
排除标准
- •A history of malignancy (other than multiple myeloma) unless all treatment of that malignancy was completed at least 2 years before consent and the participant has no evidence of disease before the of date of randomization. Exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years
- •Must not have progressed on multiple myeloma (MM) therapy at any time prior to screening
- •Have had prior treatment/therapy with: (a) Daratumumab or any other anti-cluster of differentiation 38 (CD38) therapies, (b) Focal radiation therapy within 14 days prior to randomization with the exception of palliative radiotherapy for symptomatic management but not on measurable extramedullary plasmacytoma. Radiotherapy within 14 days prior to randomization on measurable extramedullary plasmacytoma is not permitted even in the setting of palliation for symptomatic management, or (c) Plasmapheresis within 28 days of randomization
- •Be exhibiting clinical signs of meningeal or central nervous system involvement due to multiple myeloma
- •Have known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) less than (<) 50 percent (%) of predicted normal
- •Have known moderate or severe persistent asthma within the past 2 years or current uncontrolled asthma of any classification
- •Have any of the following: (a) Known history of seropositivity for human immunodeficiency virus (HIV); (b) Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]. Participants with resolved infection (that is, participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Participants with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR; (c) Seropositive for hepatitis C (anti-hepatitis C virus [HCV] antibody positive or HCV-RNA quantitation positive), except in the setting of a sustained virologic response, defined as aviremia at least 12 weeks after completion of antiviral therapy)
研究组 & 干预措施
Daratumumab + Lenalidomide
Experimental
Participants will receive 1800 milligram (mg) daratumumab by subcutaneous (SC) injection in combination with lenalidomide (orally) as maintenance therapy for a maximum of 36 cycles. Each cycle is of 28 days.
干预措施: Daratumumab (Drug)
Daratumumab + Lenalidomide
Experimental
Participants will receive 1800 milligram (mg) daratumumab by subcutaneous (SC) injection in combination with lenalidomide (orally) as maintenance therapy for a maximum of 36 cycles. Each cycle is of 28 days.
干预措施: Lenalidomide (Drug)
Lenalidomide
Active Comparator
Participants will receive lenalidomide (orally) alone as maintenance therapy for a maximum of 36 cycles. Each cycle is of 28 days.
干预措施: Lenalidomide (Drug)
结局指标
主要结局
Percentage of Participants Who Had Minimal Residual Disease (MRD) Conversion From Baseline to 12 Months After Start of Maintenance Treatment as Determined by Next Generation Sequencing (NGS)
时间窗: From randomization up to 12 months
Percentage of participants who achieved MRD negative (MRD conversion) status from baseline to 12 months after maintenance treatment was defined as percentage of participants who were MRD positive at baseline (randomization) and achieved MRD negative status (at 10\^-5) during the time period from randomization to 12 months plus 2 months window, but prior to progressive disease (PD) and subsequent anti-myeloma therapy.
次要结局
- Progression-free Survival (PFS)(From randomization to either disease progression or death (up to 7.1 years))
- Percentage of Participants Who Achieved Overall MRD (at 10^-5) Negativity Conversion From Baseline to End of Study Treatment Period(From randomization up to 30 days after last dose of study treatment or disease progression or initiation of subsequent therapy, whichever occurs first (up to 3 years))
- Percentage of Participants Who Achieved Durable (Greater Than or Equal to [>=] 12 Months) MRD Negative Status (10^-5)(From randomization up to 30 days after last dose of study treatment or disease progression or initiation of subsequent therapy, whichever occurs first (up to 3 years))
- Response Rates by International Myeloma Working Group (IMWG) 2016 Criteria(From randomization up to 30 days after last dose of study treatment or disease progression or initiation of subsequent therapy, whichever occurs first (up to 3 years))
- Overall Survival (OS)(From randomization up to 7.1 years)
- Duration of Complete Response (CR)(From date of initial documentation of CR or sCR up to first documented disease progression or death due to disease progression whichever occurs first (up to 7.1 years))
- Health-related Quality of Life: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires-C30 (EORTC QLQ-C30)(From baseline (Cycle 1 Day 1) up to 7.1 years)
- Health-related Quality of Life: Change From Baseline in European Quality of Life Five Dimensions Questionnaire-5-level (EQ-5D-5L)(From baseline (Cycle 1 Day 1) up to 7.1 years)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(From Cycle 1 Day 1 up to 30 days after the last study treatment or day prior to start of subsequent antimyeloma therapy (up to 7.1 years))
- Health-related Quality of Life: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaires-Multiple Myeloma Module (EORTC QLQ-MY20)(From baseline (Cycle 1 Day 1) up to 7.1 years)
研究者
研究点 (144)
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相关资讯
Daratumumab Plus Lenalidomide Significantly Enhances Outcomes in Newly Diagnosed Multiple Myeloma- The AURIGA trial demonstrated a significantly higher MRD-negative conversion rate at 12 months with daratumumab plus lenalidomide compared to lenalidomide alone (50.5% vs 10.8%).
- Patients receiving daratumumab and lenalidomide achieved deeper complete responses (75.8% vs 61%) and improved progression-free survival at 30 months (83% vs 66%).
- The combination therapy showed a 47% reduction in the risk of progression or death, favoring daratumumab and lenalidomide over lenalidomide alone.
- While adverse events were slightly higher in the daratumumab/lenalidomide arm, no new safety signals were identified beyond expected cytopenia and infection.last yearDaratumumab/Lenalidomide Combo Improves MRD Negativity in Myeloma Maintenance- A post hoc analysis of the AURIGA trial reveals that adding daratumumab to lenalidomide enhances minimal residual disease (MRD)-negativity conversion rates in multiple myeloma patients post-transplant.
- The benefit of the daratumumab/lenalidomide combination was observed across various clinically relevant subgroups, including different age groups, races, and ISS stages.
- The findings support the use of a doublet regimen with daratumumab and lenalidomide in the maintenance setting, complementing data from the PERSEUS and GRIFFIN trials.
- The AURIGA study's results indicate a statistically significant improvement in MRD-negative conversion rates compared to lenalidomide alone, reinforcing the efficacy of the combination therapy.last yearAdvances in Multiple Myeloma Treatment Highlighted at IMS 2024- Updated results from the TRIMM-2 study showed that talquetamab, daratumumab, and pomalidomide achieved an 82% overall response rate in relapsed/refractory multiple myeloma.
- The CEPHEUS trial demonstrated that adding subcutaneous daratumumab to VRd improved minimal residual disease negativity in newly diagnosed, transplant-ineligible multiple myeloma patients.
- CARTITUDE-4 trial updates revealed ciltacabtagene autoleucel reduced the risk of death by 45% compared to standard care in lenalidomide-refractory multiple myeloma.
- The RedirecTT-1 study indicated that talquetamab plus teclistamab delivered high rates of durable responses in triple-class exposed relapsed/refractory multiple myeloma.last yearDaratumumab-Based Regimens Deepen Responses and Improve MRD Negativity in Multiple Myeloma- Daratumumab plus lenalidomide maintenance significantly increased MRD-negative conversion rates compared to lenalidomide alone in transplant-eligible newly diagnosed multiple myeloma patients.
- The addition of daratumumab to VRd improved MRD negativity rates in transplant-ineligible or deferred newly diagnosed multiple myeloma patients.
- D-VRd followed by D-R maintenance resulted in higher rates of overall MRD-negativity in revised high-risk multiple myeloma subgroups.2 years ago