A Safety and Efficacy Study of JNJ-68284528 (Ciltacabtagene Autoleucel) Out-of-Specification (OOS) for Commercial Release in Patients With Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 86
- 试验地点
- 18
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of cilta-cel out-of-specification (OOS).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Eligible for treatment with cilta-cel per United States prescribing information (USPI) or locally approved label
- •Participant is suffering from serious or life threatening multiple myeloma per USPI (or locally approved label, respectively), and re-apheresis, re-manufacturing, or other anti-myeloma directed therapies is not considered feasible or adequate per investigator
- •Has adequate general health status and organ function per investigator assessment and meets the criteria to receive cilta-cel out-of-specifications (OOS)
- •Meets the criteria to receive lymphodepleting chemotherapy
- •A woman of childbearing potential must have a negative highly sensitive serum (beta-human chorionic gonadotropin [beta-hCG]) pregnancy test during screening and prior to the first dose of cyclophosphamide and fludarabine
排除标准
- •History of active uncontrolled infection or condition where an administration of cilta-cel OOS constitutes serious health risk to the participant
- •Known allergies, hypersensitivity, or intolerance to the excipients of cilta-cel OOS including dimethyl sulfoxide (DMSO), dextran 40, or residual kanamycin per USPI
- •Hepatitis B infection
- •Hepatitis C infection defined as (anti hepatitis C virus [HCV] antibody positive or detectable HCV ribonucleic acid [RNA]) or known to have a history of hepatitis C
- •Seropositive for human immunodeficiency virus (HIV)
- •Uncontrolled autoimmune disease
研究组 & 干预措施
Ciltacabtagene Autoleucel (Cilta-cel)
Eligible participants will receive bridging therapy (that is, anti-plasma cell directed treatment) based on participant's clinical status and timing of availability of cilta-cel (JNJ-68284528) along with lymphodepleting chemotherapy (cyclophosphamide 300 milligrams per meter square [mg/m^2] intravenous [IV] and fludarabine 30 mg/m^2 IV daily, for 3 days). After 5 to 7 days of initiating lymphodepleting chemotherapy, participants will receive a single IV infusion of cilta-cel (JNJ-68284528) at a total targeted dose of 0.75*10^6 chimeric antigen receptor (CAR)-positive viable T cells per kilogram (cells/kg).
干预措施: Cilta-cel (Drug)
Ciltacabtagene Autoleucel (Cilta-cel)
Eligible participants will receive bridging therapy (that is, anti-plasma cell directed treatment) based on participant's clinical status and timing of availability of cilta-cel (JNJ-68284528) along with lymphodepleting chemotherapy (cyclophosphamide 300 milligrams per meter square [mg/m^2] intravenous [IV] and fludarabine 30 mg/m^2 IV daily, for 3 days). After 5 to 7 days of initiating lymphodepleting chemotherapy, participants will receive a single IV infusion of cilta-cel (JNJ-68284528) at a total targeted dose of 0.75*10^6 chimeric antigen receptor (CAR)-positive viable T cells per kilogram (cells/kg).
干预措施: Lymphodepleting Therapy (Cyclophosphamide and Fludarabine) (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: From Day 1 (post infusion) up to 18.6 months
ORR is defined as the percentage of participants who had partial response (PR) or better (sCR+CR+VGPR+PR) according to the International Myeloma Working Group (IMWG) response criteria, as assessed by the investigator. CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and less than (\<) 5 percentage (%) plasma cells (PCs) in bone marrow; sCR: CR+Normal free light chain ratio and absence of clonal cells in bone marrow by immunohistochemistry or immuno fluorescence; PR: greater than equal to (\>=) 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>= 90 percentage (%) or to \<200 mg/24 hours; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \<100 mg per 24 hour.
次要结局
- Partial Response (PR) Rate(From Day 1 (post infusion) up to 18.6 months)
- Number of Participants With Treatment-emergent Adverse Event of Special Interest (AESIs): Cytokine Release Syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity (ICANS), Other Neurotoxicities, and Secondary Primary Malignancies(From Day 1 up to 100 days post cilta-cel OOS infusion (Up to 100 days))
- Very Good Partial Response (VGPR) Rate(From Day 1 (post infusion) up to 18.6 months)
- Complete Response (CR) Rate(From Day 1 (post infusion) up to 18.6 months)
- Clinical Benefit Rate (CBR)(From Day 1 (post infusion) up to 18.6 months)
- Number of Participants With Treatment-emergent Adverse Event of Special Interest (AESIs): Prolonged and Recurrent Cytopenias(From Day 1 up to 100 days post cilta-cel OOS infusion (Up to 100 days))
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(From Day 1 up to 100 days post cilta-cel OOS infusion (Up to 100 days))
- Number of Participants by Worst Grade Abnormalities in Clinical Laboratory Tests: Hematology (Including Coagulation) and Chemistry After Cilta-cel OOS Infusion(From Day 1 (post infusion) up to 18.6 months)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity(From Day 1 up to 100 days post cilta-cel OOS infusion (Up to 100 days))
- Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs)(From Day 1 up to 100 days post cilta-cel OOS infusion (Up to 100 days))
- Stringent Complete Response (sCR) Rate(From Day 1 (post infusion) up to 18.6 months)
- Duration of Response (DOR)(From Day 1 (post infusion) up to 18.6 months)
- Progression Free Survival (PFS)(From Day 1 (post infusion) up to 18.6 months)
- Overall Survival (OS)(From Day 1 (post infusion) up to 18.6 months)
- Minimal Residual Disease (MRD)-Negative Rate(From Day 1 (post infusion) up to 18.6 months)
- Number of Participants With Presence of Replication Competent Lentivirus(Predose, 3, 6, 12 months after cilta-cel infusion on Day 1)