A Phase 2 Multicohort Trial to Further Characterize the Efficacy and Safety of Ciltacabtagene Autoleucel
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 25
- 主要终点
- Minimal Residual Disease (MRD)-negative Complete Response (CR) After Cilta-cel Infusion
研究概览
简要总结
The purpose of this study is to evaluate how well (efficacy) cilta-cel works when given with a fludarabine-free lymphodepletion regimen (a process of reducing the number of lymphocytes, a type of white blood cell in the body, typically through chemotherapy), or an alternative administration of cilta-cel infusion following a cyclophosphamide and fludarabine lymphodepletion regimen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Documented diagnosis of newly diagnosed multiple myeloma (NDMM) according to the most recent international myeloma working group (IMWG) diagnostic criteria and measurable disease at diagnosis (prior to start of any anti-myeloma therapy): Serum monoclonal paraprotein (M-protein) level greater than equal to (>=)1.0 grams per deciliter (g/dL) or urine M-protein level >= 200 milligrams (mg)/24 hours; or light chain multiple myeloma in whom the only measurable disease is by serum free light chain (FLC) levels in the serum: involved serum free light chain >= 10 mg/dL and abnormal serum free light chain ratio
- •Not considered a candidate for high-dose chemotherapy with stem cell transplantation due to: (a) Advanced age; or (b) Presence of comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with stem cell transplantation; or (c) Participant refusal of high-dose chemotherapy with stem cell transplantation as initial treatment
- •Participant must have received at least 3 cycles and no more than 5 cycles of induction therapy. Initially, only participants receiving triplet induction therapy with DRd or VRd will be enrolled. Only after sponsor notification, participants receiving quadruplet DVRd induction therapy may be enrolled (screening can commence as early as during Cycle 3 of induction). Participants must have achieved >= partial response (PR) on the most recent disease assessment to be enrolled
- •Eastern cooperative oncology group (ECOG) Performance Status score of 0 or 1
- •Must be willing and able to adhere to the lifestyle restrictions specified in the protocol
排除标准
- •Frailty index of >= 2 according to Myeloma Geriatric Assessment score
- •Known allergies, hypersensitivity, or intolerance to study intervention or its active agents
- •Grade 2 or higher ongoing non-hematologic toxicity due to induction therapy, with the exception of grade 2 peripheral neuropathy due to bortezomib
- •Participants who require continuous supplemental oxygen
研究组 & 干预措施
Cohort A
Participants will undergo apheresis and continue to receive 1-2 more cycles of the induction regimen (DRd, VRd or DVRd regimen, in accordance with institution standard of care, and is not considered study treatment) that they were receiving prior to screening. After completion of induction therapy, participants will receive a conditioning regimen of cyclophosphamide daily for 3 days, followed by cilta-cel IV infusion on Day 1. Participants will later enter the post-treatment phase, which will start on Day 113 and last until end of study or cohort completion.
干预措施: Cilta-cel (Drug)
Cohort A
Participants will undergo apheresis and continue to receive 1-2 more cycles of the induction regimen (DRd, VRd or DVRd regimen, in accordance with institution standard of care, and is not considered study treatment) that they were receiving prior to screening. After completion of induction therapy, participants will receive a conditioning regimen of cyclophosphamide daily for 3 days, followed by cilta-cel IV infusion on Day 1. Participants will later enter the post-treatment phase, which will start on Day 113 and last until end of study or cohort completion.
干预措施: Cyclophosphamide (Drug)
Cohort A
Participants will undergo apheresis and continue to receive 1-2 more cycles of the induction regimen (DRd, VRd or DVRd regimen, in accordance with institution standard of care, and is not considered study treatment) that they were receiving prior to screening. After completion of induction therapy, participants will receive a conditioning regimen of cyclophosphamide daily for 3 days, followed by cilta-cel IV infusion on Day 1. Participants will later enter the post-treatment phase, which will start on Day 113 and last until end of study or cohort completion.
干预措施: Induction therapy (Drug)
Cohort B
Participants will undergo apheresis and continue to receive 1-2 more cycles of the induction regimen (DRd, VRd or DVRd regimen, in accordance with institution standard of care, and is not considered study treatment) that they were receiving prior to screening. After completion of induction therapy, participants will receive a conditioning regimen of cyclophosphamide and fludarabine daily for 3 days, followed by Ciltacel IV infusion on Day 1. Participants will later enter the post-treatment phase, which will start on Day 113 and last until end of study or cohort completion.
干预措施: Induction therapy (Drug)
Cohort B
Participants will undergo apheresis and continue to receive 1-2 more cycles of the induction regimen (DRd, VRd or DVRd regimen, in accordance with institution standard of care, and is not considered study treatment) that they were receiving prior to screening. After completion of induction therapy, participants will receive a conditioning regimen of cyclophosphamide and fludarabine daily for 3 days, followed by Ciltacel IV infusion on Day 1. Participants will later enter the post-treatment phase, which will start on Day 113 and last until end of study or cohort completion.
干预措施: Cyclophosphamide (Drug)
Cohort B
Participants will undergo apheresis and continue to receive 1-2 more cycles of the induction regimen (DRd, VRd or DVRd regimen, in accordance with institution standard of care, and is not considered study treatment) that they were receiving prior to screening. After completion of induction therapy, participants will receive a conditioning regimen of cyclophosphamide and fludarabine daily for 3 days, followed by Ciltacel IV infusion on Day 1. Participants will later enter the post-treatment phase, which will start on Day 113 and last until end of study or cohort completion.
干预措施: Cilta-cel (Drug)
Cohort B
Participants will undergo apheresis and continue to receive 1-2 more cycles of the induction regimen (DRd, VRd or DVRd regimen, in accordance with institution standard of care, and is not considered study treatment) that they were receiving prior to screening. After completion of induction therapy, participants will receive a conditioning regimen of cyclophosphamide and fludarabine daily for 3 days, followed by Ciltacel IV infusion on Day 1. Participants will later enter the post-treatment phase, which will start on Day 113 and last until end of study or cohort completion.
干预措施: Fludarabine (Drug)
结局指标
主要结局
Minimal Residual Disease (MRD)-negative Complete Response (CR) After Cilta-cel Infusion
时间窗: At least 12 months after Cilta-cel infusion on Day 1
Participants in CR or better who achieve MRD-negative status at 12 months after cilta-cel infusion with a sensitivity of 10\^-5, prior to progressive disease (PD) or subsequent anti-myeloma therapy will be reported.
Minimal Residual Disease (MRD)-negative Complete Response (CR) After Cilta-cel Infusion
时间窗: At least 12 months after Cilta-cel infusion on Day 1
Participants in CR or better who achieve MRD-negative status at 12 months after cilta-cel infusion with a sensitivity of 10\^-5, prior to progressive disease (PD) or subsequent anti-myeloma therapy will be reported.
次要结局
- Overall MRD-negative CR Rate(From study start until progressive disease, subsequent therapy or end of study, whichever is earlier (Up to 3 years and 4 months))
- CR or better status(From study start until progressive disease, subsequent therapy or end of study, whichever is earlier (Up to 3 years and 4 months))
- Progression Free Survival (PFS)(From study start until progressive disease, subsequent therapy or end of study, whichever is earlier (Up to 3 years and 4 months))
- Overall Survival (OS)(Up to 3 years and 4 months)
- Number of Participants with Adverse Event (AE) by Severity(Up to 3 years and 4 months)
- Number of Participants with Abnormalities in Laboratory Parameters(Up to 3 years and 4 months)
- Levels of Cilta-cel T-Cell Expansion, and Persistence(Up to 3 years and 4 months)
- Number of Participants with Anti-Cilta-Cel Antibodies(Up to 3 years and 4 months)
- Percentage of Participants with Presence of Replication-competent Lentivirus (RCL)(Up to 3 years and 4 months)