A Phase 3 Randomized Study Comparing Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) Followed by Ciltacabtagene Autoleucel Versus Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) Followed by Autologous Stem Cell Transplant (ASCT) in Participants With Newly Diagnosed Multiple Myeloma Who Are Transplant Eligible
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 759
- 试验地点
- 133
- 主要终点
- Progression free survival (PFS)
研究概览
简要总结
The purpose of this study is to compare the efficacy of Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) followed by Ciltacabtagene Autoleucel versus Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) followed by Autologous Stem Cell Transplant (ASCT) in newly diagnosed multiple myeloma patients.
详细描述
Multiple myeloma (MM) is a malignant plasma cell disorder characterized by the production of monoclonal immunoglobulin (Ig) proteins or protein fragments (M proteins) that have lost their function.
JNJ-68284528 (ciltacabtagene autoleucel [cilta-cel]) is an autologous chimeric antigen receptor T cell (CAR-T) therapy that targets B-cell maturation antigen (BCMA) that is being evaluated to treat participants with multiple myeloma. The primary hypothesis is that in transplant-eligible participants with newly diagnosed multiple myeloma (NDMM), cilta-cel will significantly improve progression-free survival (PFS) and Sustained MRD-negative CR rate compared with Autologous Stem Cell Transplant (ASCT).
Approximately 750 participants (375 per arm) will be randomly assigned in a 1:1 ratio into 2 arms.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with documented NDMM according to IMWG diagnostic criteria, for whom high-dose therapy and ASCT are part of the intended initial treatment plan.
- •Measurable disease, as assessed by central laboratory, at screening as defined by any of the following:
- •Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or
- •Light chain MM without measurable disease in serum or urine: serum Ig free-light chain (FLC) ≥10 mg/dL and abnormal serum Ig kappa lambda FLC ratio.
- •ECOG performance status of grade 0 or 1
- •Clinical laboratory values within prespecified range.
排除标准
- •Prior treatment with CAR-T therapy directed at any target.
- •Any prior BCMA target therapy.
- •Any prior therapy for MM or smoldering myeloma other than a short course of corticosteroids
- •Received a strong cytochrome P450 (CYP)3A4 inducer within 5 half-lives prior to randomization
- •Received or plans to receive any live, attenuated vaccine (except for COVID-19 vaccines) within 4 weeks prior to randomization.
- •Known active, or prior history of central nervous system (CNS) involvement or clinical signs of meningeal involvement of MM
- •Stroke or seizure within 6 months of signing Informed Consent Form (ICF)
研究组 & 干预措施
Arm B: DVRd followed by Ciltacabtagene Autoleucel
Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRd) for 6 induction cycles.
Participants will receive a conditioning regimen (cyclophosphamide 300 mg/m^2 intravenous [IV] and fludarabine 30 mg/m^2 IV daily for 3 days) and Cilta-cel infusion 0.75*10^6 chimeric antigen receptor (CAR)-positive viable T cells/kilogram (kg), followed by lenalidomide post CAR-T cell therapy for 2 years
Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6.
Bortezomib SC 1.3 mg/m^2 on days 1, 4, 8, and 11 of each cycle 1-6.
Lenalidomide orally, 25 mg on days 1 to 21 of each cycle 1-6.
Dexamethasone orally, 40 mg once a week on days 1, 8, 15 and 22 of each cycle 1-6.
Each cycle will consist of 28 days.
Lenalidomide maintenance orally 10 to 15 mg on days 1 to 28 (continuously) until confirmed progressive disease or unacceptable toxicity or for a maximum of 2 years
干预措施: Daratumumab (Drug)
Arm B: DVRd followed by Ciltacabtagene Autoleucel
Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRd) for 6 induction cycles.
Participants will receive a conditioning regimen (cyclophosphamide 300 mg/m^2 intravenous [IV] and fludarabine 30 mg/m^2 IV daily for 3 days) and Cilta-cel infusion 0.75*10^6 chimeric antigen receptor (CAR)-positive viable T cells/kilogram (kg), followed by lenalidomide post CAR-T cell therapy for 2 years
Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6.
Bortezomib SC 1.3 mg/m^2 on days 1, 4, 8, and 11 of each cycle 1-6.
Lenalidomide orally, 25 mg on days 1 to 21 of each cycle 1-6.
Dexamethasone orally, 40 mg once a week on days 1, 8, 15 and 22 of each cycle 1-6.
Each cycle will consist of 28 days.
Lenalidomide maintenance orally 10 to 15 mg on days 1 to 28 (continuously) until confirmed progressive disease or unacceptable toxicity or for a maximum of 2 years
干预措施: Bortezomib (Drug)
Arm B: DVRd followed by Ciltacabtagene Autoleucel
Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRd) for 6 induction cycles.
Participants will receive a conditioning regimen (cyclophosphamide 300 mg/m^2 intravenous [IV] and fludarabine 30 mg/m^2 IV daily for 3 days) and Cilta-cel infusion 0.75*10^6 chimeric antigen receptor (CAR)-positive viable T cells/kilogram (kg), followed by lenalidomide post CAR-T cell therapy for 2 years
Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6.
Bortezomib SC 1.3 mg/m^2 on days 1, 4, 8, and 11 of each cycle 1-6.
Lenalidomide orally, 25 mg on days 1 to 21 of each cycle 1-6.
Dexamethasone orally, 40 mg once a week on days 1, 8, 15 and 22 of each cycle 1-6.
Each cycle will consist of 28 days.
Lenalidomide maintenance orally 10 to 15 mg on days 1 to 28 (continuously) until confirmed progressive disease or unacceptable toxicity or for a maximum of 2 years
干预措施: Lenalidomide (Drug)
Arm B: DVRd followed by Ciltacabtagene Autoleucel
Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRd) for 6 induction cycles.
Participants will receive a conditioning regimen (cyclophosphamide 300 mg/m^2 intravenous [IV] and fludarabine 30 mg/m^2 IV daily for 3 days) and Cilta-cel infusion 0.75*10^6 chimeric antigen receptor (CAR)-positive viable T cells/kilogram (kg), followed by lenalidomide post CAR-T cell therapy for 2 years
Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6.
Bortezomib SC 1.3 mg/m^2 on days 1, 4, 8, and 11 of each cycle 1-6.
Lenalidomide orally, 25 mg on days 1 to 21 of each cycle 1-6.
Dexamethasone orally, 40 mg once a week on days 1, 8, 15 and 22 of each cycle 1-6.
Each cycle will consist of 28 days.
Lenalidomide maintenance orally 10 to 15 mg on days 1 to 28 (continuously) until confirmed progressive disease or unacceptable toxicity or for a maximum of 2 years
干预措施: Dexamethasone (Drug)
Arm B: DVRd followed by Ciltacabtagene Autoleucel
Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRd) for 6 induction cycles.
Participants will receive a conditioning regimen (cyclophosphamide 300 mg/m^2 intravenous [IV] and fludarabine 30 mg/m^2 IV daily for 3 days) and Cilta-cel infusion 0.75*10^6 chimeric antigen receptor (CAR)-positive viable T cells/kilogram (kg), followed by lenalidomide post CAR-T cell therapy for 2 years
Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6.
Bortezomib SC 1.3 mg/m^2 on days 1, 4, 8, and 11 of each cycle 1-6.
Lenalidomide orally, 25 mg on days 1 to 21 of each cycle 1-6.
Dexamethasone orally, 40 mg once a week on days 1, 8, 15 and 22 of each cycle 1-6.
Each cycle will consist of 28 days.
Lenalidomide maintenance orally 10 to 15 mg on days 1 to 28 (continuously) until confirmed progressive disease or unacceptable toxicity or for a maximum of 2 years
干预措施: Cilta-cel (Drug)
Arm B: DVRd followed by Ciltacabtagene Autoleucel
Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRd) for 6 induction cycles.
Participants will receive a conditioning regimen (cyclophosphamide 300 mg/m^2 intravenous [IV] and fludarabine 30 mg/m^2 IV daily for 3 days) and Cilta-cel infusion 0.75*10^6 chimeric antigen receptor (CAR)-positive viable T cells/kilogram (kg), followed by lenalidomide post CAR-T cell therapy for 2 years
Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6.
Bortezomib SC 1.3 mg/m^2 on days 1, 4, 8, and 11 of each cycle 1-6.
Lenalidomide orally, 25 mg on days 1 to 21 of each cycle 1-6.
Dexamethasone orally, 40 mg once a week on days 1, 8, 15 and 22 of each cycle 1-6.
Each cycle will consist of 28 days.
Lenalidomide maintenance orally 10 to 15 mg on days 1 to 28 (continuously) until confirmed progressive disease or unacceptable toxicity or for a maximum of 2 years
干预措施: Cyclophosphamide (Drug)
Arm B: DVRd followed by Ciltacabtagene Autoleucel
Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRd) for 6 induction cycles.
Participants will receive a conditioning regimen (cyclophosphamide 300 mg/m^2 intravenous [IV] and fludarabine 30 mg/m^2 IV daily for 3 days) and Cilta-cel infusion 0.75*10^6 chimeric antigen receptor (CAR)-positive viable T cells/kilogram (kg), followed by lenalidomide post CAR-T cell therapy for 2 years
Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6.
Bortezomib SC 1.3 mg/m^2 on days 1, 4, 8, and 11 of each cycle 1-6.
Lenalidomide orally, 25 mg on days 1 to 21 of each cycle 1-6.
Dexamethasone orally, 40 mg once a week on days 1, 8, 15 and 22 of each cycle 1-6.
Each cycle will consist of 28 days.
Lenalidomide maintenance orally 10 to 15 mg on days 1 to 28 (continuously) until confirmed progressive disease or unacceptable toxicity or for a maximum of 2 years
干预措施: Fludarabine (Drug)
Arm A: DVRd + ASCT+DVRd (Standard Therapy)
Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRd) for 4 induction cycles. Followed by ASCT and 2 cycles of DVRd consolidation, and lenalidomide maintenance therapy for 2 years
Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6.
Bortezomib SC 1.3 mg/m^2 on days 1, 4, 8, and 11 of each cycle 1-6. Lenalidomide orally, 25 mg on days 1 to 21 of each cycle 1-6. Dexamethasone orally, 40 mg once a week on days 1, 8, 15 and 22 of each cycle 1-6.
Each cycle will consist 28 days.
Lenalidomide maintenance orally 10 to 15 mg on days 1 to 28 (continuously) until confirmed progressive disease or unacceptable toxicity or for a maximum of 2 years
干预措施: Daratumumab (Drug)
Arm A: DVRd + ASCT+DVRd (Standard Therapy)
Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRd) for 4 induction cycles. Followed by ASCT and 2 cycles of DVRd consolidation, and lenalidomide maintenance therapy for 2 years
Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6.
Bortezomib SC 1.3 mg/m^2 on days 1, 4, 8, and 11 of each cycle 1-6. Lenalidomide orally, 25 mg on days 1 to 21 of each cycle 1-6. Dexamethasone orally, 40 mg once a week on days 1, 8, 15 and 22 of each cycle 1-6.
Each cycle will consist 28 days.
Lenalidomide maintenance orally 10 to 15 mg on days 1 to 28 (continuously) until confirmed progressive disease or unacceptable toxicity or for a maximum of 2 years
干预措施: Bortezomib (Drug)
Arm A: DVRd + ASCT+DVRd (Standard Therapy)
Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRd) for 4 induction cycles. Followed by ASCT and 2 cycles of DVRd consolidation, and lenalidomide maintenance therapy for 2 years
Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6.
Bortezomib SC 1.3 mg/m^2 on days 1, 4, 8, and 11 of each cycle 1-6. Lenalidomide orally, 25 mg on days 1 to 21 of each cycle 1-6. Dexamethasone orally, 40 mg once a week on days 1, 8, 15 and 22 of each cycle 1-6.
Each cycle will consist 28 days.
Lenalidomide maintenance orally 10 to 15 mg on days 1 to 28 (continuously) until confirmed progressive disease or unacceptable toxicity or for a maximum of 2 years
干预措施: Dexamethasone (Drug)
Arm A: DVRd + ASCT+DVRd (Standard Therapy)
Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRd) for 4 induction cycles. Followed by ASCT and 2 cycles of DVRd consolidation, and lenalidomide maintenance therapy for 2 years
Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6.
Bortezomib SC 1.3 mg/m^2 on days 1, 4, 8, and 11 of each cycle 1-6. Lenalidomide orally, 25 mg on days 1 to 21 of each cycle 1-6. Dexamethasone orally, 40 mg once a week on days 1, 8, 15 and 22 of each cycle 1-6.
Each cycle will consist 28 days.
Lenalidomide maintenance orally 10 to 15 mg on days 1 to 28 (continuously) until confirmed progressive disease or unacceptable toxicity or for a maximum of 2 years
干预措施: Lenalidomide (Drug)
结局指标
主要结局
Progression free survival (PFS)
时间窗: up to 10 years ( or 300 PFS events)
Progression free survival is defined as the time from the date of randomization to the date of first documented PD, as defined in the IMWG criteria, or death due to any cause, whichever occurs first
Sustained MRD-negative CR
时间窗: up to 24 months
Sustained MRD-negative CR is defined as being MRD negative by bone marrow aspirate, as determined by NGS with a sensitivity of at least 10-5, and meeting the IMWG criteria for CR, and with MRD-negativity status confirmed at a minimum 12 months apart and without any examination showing MRD-positive status or PD in between.
次要结局
- Change from Baseline in Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30) Scale Score(up to 17 years)
- Change from Baseline in Health-Related Quality of Life as Assessed by MySIm-Q Scale Score(up to 17 years)
- Change from Baseline in Health-Related Quality of Life as Assessed by European Quality of Life - 5 Dimensions-5 Levels (EQ-5D-5L) Scale Scor(up to 17 years)
- Overall Response (OR)(up to 17 years)
- Complete Response (CR) or better status(up to 17 years)
- Progression Free Survival on Next-line Therapy (PFS2)(up to 17 years)
- Overall Survival (OS)(up to 17 years)
- Overall Minimal Residual Disease (MRD) -negative CR(up to 17 years)
- Time to subsequent antimyeloma therapy(up to 17 years)
- Change from Baseline in Health-Related Quality of Life as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score(up to 17 years)
- Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)(up to 280 days)