NCT03548207已完成1 期
A Phase 1b-2, Open-Label Study of JNJ-68284528, A Chimeric Antigen Receptor T-Cell (CAR-T) Therapy Directed Against BCMA in Subjects With Relapsed or Refractory Multiple Myeloma
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 126
- 试验地点
- 21
- 主要终点
- Phase 1b: Number of Participants With Adverse Events as Per Severity
研究概览
简要总结
The purpose of the study is to characterize safety of JNJ-68284528 and establish the recommended Phase 2 dose (RP2D) (Phase 1b) and to evaluate the efficacy of JNJ-68284528 (Phase 2).
详细描述
This study will evaluate the safety and efficacy of JNJ-68284528. The study will include two phases. In Phase1b the study will enroll adults with multiple myeloma with interval assessments for potential dose escalation or de-escalation in subsequent participants. The dose selected at the completion of phase 1b will be used in Phase 2. Following consent, enrolled participants will undergo an apheresis procedure to collect cells for manufacture of investigational drug product (JNJ-68284528). Following manufacture of the drug product, participants will undergo lymphodepletion prior to infusion of JNJ-68284528. Participants will be followed for at least 2 years after study drug infusion, with long-term 15 year follow-up on a separate study. The study will evaluate safety, biomarkers, pharmacokinetic/pharmacodynamic evaluations and efficacy.
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
- •Have documented diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria
- •Have measurable disease at Screening as defined by any of the following a) Serum monoclonal paraprotein (M-protein) level more than or equal to (>=) 1.0 gram per deciliter(g/dL) or urine M-protein level >=200 milligram per 24 hours (mg/24hr); or b) Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin free light chain 10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio
- •Have received at least 3 prior multiple myeloma treatment lines of therapy or are double refractory to an immunomodulatory drug (IMiD) and proteasome inhibitor (PI) (refractory multiple myeloma as defined by IMWG consensus criteria). Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single lines of therapy a) Undergone at least 1 complete cycle of treatment for each line of therapy, unless progressive disease (PD) was the best response to the regimen
- •Have received as part of previous therapy a PI, an IMiD, and an anti-CD38 antibody
- •Participant must have documented evidence of progressive disease based on investigator's determination of response by the IMWG criteria on or within 12 months of their last line of therapy. Confirmation may be from either central or local testing. Also, participants with documented evidence of progressive disease (as above) within the previous 6 months and who are refractory or non-responsive to their most recent line of therapy afterwards are eligible
- •Have Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0 or 1
排除标准
- •Have received prior treatment with chimeric antigen receptor T (CAR-T) therapy directed at any target
- •Have received any therapy that is targeted to B-cell maturation antigen (BCMA)
- •Have following cardiac conditions: a) New York Heart Association (NYHA) stage III or IV congestive heart failure b) Myocardial infarction or coronary artery bypass graft (CABG) less than or equal to (<=) 6 months prior to enrollment c) History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration d) History of severe non-ischemic cardiomyopathy e) Impaired cardiac function (left ventricular ejection fraction [LVEF] less than [<]45%) as assessed by echocardiogram or multiple-gated acquisition (MUGA) scan (performed less than or equal to (<=) 8 weeks of apheresis)
- •Received a cumulative dose of corticosteroids equivalent to >= 70 mg of prednisone within the 7 days prior to apheresis
- •Have received either of the following: a) An allogenic stem cell transplant within 6 months before apheresis. Participants who received an allogeneic transplant must be off all immunosuppressive medications for 6 weeks without signs of graft-versus-host disease (GVHD) b) An autologous stem cell transplant less than or equal to (<=) 12 weeks before apheresis
- •Have known active, or prior history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma
研究组 & 干预措施
JNJ-68284528
Experimental
After lymphodepletion JNJ-68284528 will be administered as a single infusion.
干预措施: JNJ-68284528 (Biological)
结局指标
主要结局
Phase 1b: Number of Participants With Adverse Events as Per Severity
时间窗: Day 1 up to 45.2 months
An AE was any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.
Phase 2: Overall Response Rate (ORR)
时间窗: Day 1 up to 45.2 months
ORR was defined as the percentage of participants who achieved partial response (PR) or better according to international myeloma working group (IMWG) criteria. IMWG criteria for PR: greater than or equal to (\>=) 50 percent (%) reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>=90% or to less than (\<) 200 milligrams (mg) per 24 hours. If the serum and urine M-protein were not measurable, a decrease of \>=50% in the difference between involved and uninvolved free light chain (FLC) levels was required in place of the M-protein criteria. If serum and urine M-protein were not measurable, and serum free light assay was also not measurable, \>=50% reduction in bone marrow plasma cells (PCs) was required in place of M-protein, provided baseline bone marrow PC percentage was \>=30%. In addition to the above criteria, if present at baseline, a \>=50% reduction in the size of soft tissue plasmacytomas was also required.
次要结局
- Phase 1b and Phase 2: Maximum Observed Plasma Concentration (Cmax) of JNJ-68284528 Transgene(Pre and post dose on Day 1, and Days 2, 3, 7, 10, 14, 21, 28, 42, 56, 78, 100, then every 4 weeks up to 1 year, and at the time of progressive disease or at study completion for participants without progressive disease (up to approximately 2.5 years))
- Phase 1b and Phase 2: T Cell Persistence After a Single Infusion of JNJ-68284528(Pre and post dose on Day 1 and Days 2, 3, 7, 10, 14, 21, 28, 42, 56, 78, 100, then every 4 weeks up to 1 year, and at the time of progressive disease or at study completion for participants without progressive disease (up to approximately 2.5 years))
- Phase 1b and Phase 2: Area Under the Plasma Concentration Versus Time Curve From Time 0 To Last Measurable Concentration (AUC0-last) of CD3+CAR+ Cells in Blood After a Single Infusion of JNJ-68284528(Pre and post dose on Day 1 and Days 2, 3, 7, 10, 14, 21, 28, 42, 56, 78, 100, then every 4 weeks up to 1 year, and at the time of progressive disease or at study completion for participants without progressive disease (up to approximately 2.5 years))
- Phase 1b and Phase 2: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinite Time (AUC0-infinity) of CD3+CAR+ Cells in Blood After a Single Infusion of JNJ-68284528(Pre and post dose on Day 1 and Days 2, 3, 7, 10, 14, 21, 28, 42, 56, 78, 100, then every 4 weeks up to 1 year, and at the time of progressive disease or at study completion for participants without progressive disease (up to approximately 2.5 years))
- Phase 1b and Phase 2: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinite Time (AUC0-infinity) of JNJ-68284528 Transgene(Pre and post dose on Day 1 and Days 2, 3, 7, 10, 14, 21, 28, 42, 56, 78, 100, then every 4 weeks up to 1 year, and at the time of progressive disease or at study completion for participants without progressive disease (up to approximately 2.5 years))
- Phase 1b and Phase 2: Maximum Observed Plasma Concentration (Cmax) of CD3+CAR+ Cells in Blood After a Single Infusion of JNJ-68284528(Pre and post dose on Day 1 and Days 2, 3, 7, 10, 14, 21, 28, 42, 56, 78, 100, then every 4 weeks up to 1 year, and at the time of progressive disease or at study completion for participants without progressive disease (up to approximately 2.5 years))
- Phase 1b and Phase 2: Very Good Partial Response (VGPR) or Better Response Rate(Pre dose (Day 1) up to 45.2 months)
- Phase 1b and Phase 2: Actual Sampling Time of Last Measurable Analyte Concentration (Tlast) of JNJ-68284528 Transgene(Pre and post dose on Day 1 and Days 2, 3, 7, 10, 14, 21, 28, 42, 56, 78, 100, then every 4 weeks up to 1 year, and at the time of progressive disease or at study completion for participants without progressive disease (up to approximately 2.5 years))
- Phase 1b and Phase 2: Time to First Response(Pre dose (Day 1) up to 45.2 months)
- Phase 1b and Phase 2: Area Under the Plasma Concentration Versus Time Curve From Time 0 To Last Measurable Concentration (AUC0-last) of JNJ-68284528 Transgene(Pre and post dose on Day 1; Days 2, 3, 7, 10, 14, 21, 28, 42, 56, 78, 100, then every 4 weeks up to 1 year, and at the time of progressive disease or at study completion for participants without progressive disease (up to approximately 2.5 years))
- Phase 1b and Phase 2: Mean Concentration of Soluble B-cell Maturation Antigen (BCMA) Levels in Serum After Single Infusion of JNJ-68284528(Days 352 and 1024)
- Phase 1b and Phase 2: Serum Systemic Cytokine Concentrations(Pre-infusion and 2 hours post infusion on Day 1, Days 2, 3, 7, 10, 14, 21, 28, 42, 56, 78, 100)
- Phase 1b and Phase 2: Maximum Observed Plasma Concentration (Cmax) of CAR-T Cells (CD3+CAR+ Cells in Blood) After a Single Infusion of JNJ-68284528(Pre and post dose on Day 1 and Days 2, 3, 7, 10, 14, 21, 28, 42, 56, 78, 100, then every 4 weeks up to 1 year, and at the time of progressive disease or at study completion for participants without progressive disease (up to approximately 2.5 years))
- Phase 1b and Phase 2: Maximum T Cell Expansion After a Single Infusion of JNJ-68284528(Pre and post dose on Day 1 and Days 2, 3, 7, 10, 14, 21, 28, 42, 56, 78, 100, then every 4 weeks up to 1 year, and at the time of progressive disease or at study completion for participants without progressive disease (up to approximately 2.5 years))
- Phase 1b and Phase 2: Percentage of Participants With Positive Antibodies to JNJ-68284528(Pre dose (Day 1) up to 2 years)
- Phase 2: Number of Participants With Adverse Events (AEs) as Per Severity(Day 1 up to 45.2 months)
- Number of Participants With Depletion of BCMA Expressing Cells(Pre dose (Day 1) up to 2 years)
- Phase 1b and Phase 2: Minimal Residual Disease (MRD) Negative Rate(Pre dose (Day 1) up to 45.2 months)
- Phase 1b and Phase 2: Duration of Response (DOR)(Pre dose (Day 1) up to first documented PD or death (up to 45.2 months))
- Phase 1b and Phase 2: Overall Survival(Pre dose (Day 1) up to 45.2 months)
- Phase 2: Patient Global Impression of Change (PGIC) Score at Days 28, 56, 78, 100(Days 28, 56, 78, 100)
- Phase 1b and Phase 2: Clinical Benefit Rate (CBR)(Pre dose (Day 1) up to 45.2 months)
- Phase 1b and Phase 2: Progression-free Survival (PFS)(Pre dose (Day 1) up to 45.2 months)
- Phase 2 (Japan Population): Change From Baseline in EuroQol Five Dimension Questionnaire (EQ-5D-5L) Utility Score at Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296 and 324(Baseline, Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296 and 324)
- Phase 2 (Japan Population): Change From Baseline in EuroQol Five Dimension Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS) Score at Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296 and 324(Baseline, Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296 and 324)
- Phase 2 (US Population): Change From Baseline in EuroQol Five Dimension Questionnaire (EQ-5D-5L) Utility Score at Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296, 324, 352 and 380(Baseline, Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296, 324, 352 and 380)
- Phase 2 (US Population): Change From Baseline in EuroQol Five Dimension Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS) Score at Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296, 324, 352 and 380(Baseline, Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296, 324, 352 and 380)
- Phase 2: Change From Baseline in Patient Global Impression of Severity (PGIS) Score at Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296, 324, 352, 380(Baseline, Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296, 324, 352, 380)
- Phase 2 (US Population): Change From Baseline in EORTC QLQ-MY20 at Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296, 324, 352 and 380(Baseline, Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296, 324, 352 and 380)
- Phase 2 (US Population): Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 Subscales at Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296, 324, 352 and 380(Baseline, Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296, 324, 352 and 380)
- Phase 2 (Japan Population): Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 Subscales at Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296 and 324(Baseline, Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296 and 324)
- Phase 2 (Japan Population): Change From Baseline in EORTC QLQ-MY20 at Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296 and 324(Baseline, Days 7, 28, 56, 78, 100, 128, 156, 184, 212, 240, 268, 296 and 324)
研究者
研究点 (21)
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