A Phase 2, Single-arm, Multi-center Trial to Determine the Efficacy and Safety of JCAR017 in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma or With Other Aggressive B-Cell Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Celgene
- 入组人数
- 113
- 试验地点
- 20
- 主要终点
- Overall Response Rate (ORR) Per Independent Review Committee in Cohorts 1, 2 and 3
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of JCAR017 in participants with aggressive B-cell non-Hodgkin lymphoma (B-NHL)
详细描述
This is a study to determine the efficacy and safety of JCAR017 in adult participants with aggressive B-cell NHL. The study will enroll participants in Europe and Japan with diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS; de novo or transformed follicular lymphoma [tFL]), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (HGBL), follicular lymphoma Grade 3B (FL3B), and primary central nervous system lymphoma (PCNSL). Participants with secondary central nervous system (CNS) involvement are allowed.
Once enrolled, participants will undergo leukapheresis to enable JCAR017 cell product generation. Upon successful JCAR017 cell product generation, participants will receive lymphodepleting chemotherapy followed by infusion of JCAR017. JCAR017 will be administered by intravenous infusion. Participants will be followed for approximately 2 years after their JCAR017 infusion for safety, disease status, survival and health-related quality of life.
Delayed adverse events following exposure to gene modified T cells will be assessed and long-term persistence of these modified T cells will continue to be monitored under a separate long-term follow-up protocol for up to 15 years after JCAR017 infusion as per competent authority guidelines.
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
- •Histological confirmation of diagnosis at last relapse
- •Adequate organ function
- •Adequate vascular access for leukapheresis procedure
排除标准
- •Prior history of malignancies, other than aggressive relapsed/refractory Non-Hodgkin Lymphoma, unless the participant has been in remission for ≥ 2 years with the exception of non-invasive malignancies
- •Received previous CD19-targeted therapy
- •Progressive vascular tumor invasion, thrombosis, or embolism
- •Other protocol-defined inclusion/exclusion criteria apply
研究组 & 干预措施
Administration of JCAR017
干预措施: JCAR017 (Drug)
结局指标
主要结局
Overall Response Rate (ORR) Per Independent Review Committee in Cohorts 1, 2 and 3
时间窗: From JCAR017 infusion until disease progression, end of study, the start of another anticancer therapy, or hemopoietic stem cell transplant (HSCT) (up to approximately 63 months)
Overall response rate (ORR) by Independent Review Committee (Cohorts 1, 2, 3). ORR is the percent of participants with best overall response of complete response (CR) or partial response (PR). Complete response via PET-CT: * Lymph nodes/extralymphatic: Score 1, 2, 3a with/without residual mass on 5-point scale * New lesions: No * Bone marrow: No FDG-avid disease Complete response via CT scan: * Lymph nodes/extralymphatic: Target nodes/nodal masses ≤ 1.5 cm longest transverse diameter. * Nonmeasured lesion: No * New lesions: No * Bone marrow: Normal Partial response via PET-CT: * Lymph nodes/extralymphatic: Score 4, 5b, reduced uptake from baseline * New lesions: No * Bone marrow: Residual uptake higher than normal, reduced from baseline Partial response via CT scan: * Lymph nodes/extralymphatic: 50% decrease in sum of diameters of \<= 6 target measurable nodes/extranodal sites * Nonmeasured lesion: No * Organ enlargement: Spleen length decreased \> 50% * New lesions: No
Overall Response Rate (ORR) Per Investigator in Cohort 4
时间窗: From JCAR017 infusion until disease progression, end of study, the start of another anticancer therapy, or hemopoietic stem cell transplant (HSCT) (up to approximately 63 months)
Overall response rate (ORR) is the percent of participants with best overall response of complete response (CR) or partial response (PR). Complete response via PET-CT: * Lymph nodes/extralymphatic: Score 1, 2, 3a with/without residual mass on 5-point scale * New lesions: No * Bone marrow: No FDG-avid disease Complete response via CT scan: * Lymph nodes/extralymphatic: Target nodes/nodal masses ≤ 1.5 cm longest transverse diameter. * Nonmeasured lesion: None * New lesions: No * Bone marrow: Normal Partial response via PET-CT: * Lymph nodes/extralymphatic: Score 4, 5b, reduced uptake from baseline * New lesions: None * Bone marrow: Residual uptake higher than normal, reduced from baseline Partial response via CT scan: * Lymph nodes/extralymphatic: 50% decrease in sum of diameters of \<= 6 target measurable nodes/extranodal sites * Nonmeasured lesion: None/normal * Organ enlargement: Spleen length decreased \> 50% * New lesions: No
Overall Response Rate (ORR) Per Investigator in Cohort 5
时间窗: From JCAR017 infusion until disease progression, end of study, the start of another anticancer therapy, or hemopoietic stem cell transplant (HSCT) (up to approximately 63 months)
Overall response rate (ORR) determined by Investigator assessment after JCAR017 infusion. The ORR is the percent of participants with best overall response (BOR) of either complete response (CR), complete response unconfirmed (Cru) or partial response (PR). Complete response (CR): * Brain imaging: No contrast enhancement * Corticosteroid dose: None * Eye examination: Normal * Cerebrospinal fluid cytology: Negative Complete response unconfirmed (CRu): * Brain imaging: No contrast enhancement, Minimal abnormality * Corticosteroid dose: Any * Eye examination: Normal, minor RPE abnormality * Cerebrospinal fluid cytology: Negative Partial response (PR): * Brain imaging: 50% decrease in enhancing tumor, no contrast enhancement. * Corticosteroid dose: Irrelevant * Eye examination: Minor RPE abnormality, decrease in vitreous cells or retinal infiltrate. * Cerebrospinal fluid cytology: Negative, persistent or suspicious
Number of Participants With Adverse Events in Cohort 7
时间窗: From leukapheresis to end of study (up to approximately 63 months)
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening (i.e., any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE. Graded according to NCI CTCAE (Version 4.03) guidelines where grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life threatening, grade 5 = death.
Number of Participants With Serious Adverse Events (SAEs) in Cohort 7
时间窗: From leukapheresis to end of study (up to approximately 63 months)
A serious adverse event (SAE) is defined as any adverse event (AE) occurring at any dose that: * Results in death; * Is life-threatening (ie, in the opinion of the Investigator, the participant is at immediate risk of death from the AE); * Requires inpatient hospitalization or prolongation of existing hospitalization (hospitalization is defined as an inpatient admission, regardless of length of stay). * Results in persistent or significant disability/incapacity (a substantial disruption of the participant's ability to conduct normal life functions); * Is a congenital anomaly/birth defect; * Constitutes an important medical event. Graded according to NCI CTCAE (Version 4.03) guidelines where grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life threatening, grade 5 = death.
Number of Participants With Increase From Baseline in Select Hematology Parameters - Cohort 7
时间窗: At Baseline and Day 29 after JCAR017 infusion
JCAR017 treatment-emergent laboratory abnormalities are defined as an abnormality that, compared to baseline, worsens by at least one grade after JCAR017 infusion. The baseline value is defined as the last available recorded value on or prior to the date of JCAR017 infusion. Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Life-threatening), Grade 5 (Death).
Number of Participants With Increase From Baseline in Select Serum Chemistry Parameters - Cohort 7
时间窗: At Baseline and Day 29 after JCAR017 infusion
JCAR017 treatment-emergent laboratory abnormalities are defined as an abnormality that, compared to baseline, worsens by at least one grade after JCAR017 infusion. The baseline value is defined as the last available recorded value on or prior to the date of JCAR017 infusion. Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Life-threatening), Grade 5 (Death).
次要结局
- Number of Participants With Adverse Events in Cohorts 1, 2, 3, 4, and 5(From leukapheresis to end of study (up to approximately 63 months))
- Number of Participants With Serious Adverse Events (SAEs) in Cohorts 1, 2, 3, 4, and 5(From leukapheresis to end of study (up to approximately 63 months))
- Number of Participants With Increase From Baseline in Select Hematology Parameters - Cohorts 1, 2, 3, 4, and 5(At Baseline and Day 29 after JCAR017 infusion)
- Number of Participants With Increase From Baseline in Select Serum Chemistry Parameters - Cohorts 1, 2, 3, 4, and 5(At Baseline and Day 29 after JCAR017 infusion)
- Overall Response Rate (ORR) in Cohort 7(From JCAR017 infusion until disease progression, end of study, the start of another anticancer therapy, or hemopoietic stem cell transplant (HSCT) (up to approximately 63 months))
- Complete Response Rate (CRR)(From JCAR017 infusion until disease progression, end of study, the start of another anticancer therapy, or hemopoietic stem cell transplant (HSCT) (up to approximately 63 months))
- Event Free Survival (EFS)(From JCAR017 infusion to death due to any reason, progressive disease, or starting a new anticancer therapy (up to approximately 63 months).)
- Progression Free Survival (PFS) Using European Medicines Agency (EMA) Criteria(From JCAR017 infusion to progressive disease or death due to any reason, whichever occurred first (up to approximately 63 months))
- Overall Survival (OS)(From the date of JCAR017 infusion to the date of death due to any reason (up to approximately 63 months).)
- Duration of Response (DOR)(From JCAR017 infusion until disease progression, death due to any reason, end of study, the start of another anticancer therapy, or hemopoietic stem cell transplant (HSCT) (up to approximately 63 months))
- Maximum Concentration (Cmax) of JCAR017 by qPCR(At baseline and up until 24 months post JCAR017 infusion)
- Time to Peak Concentration (Tmax) of JCAR017 by qPCR(At baseline and up until 24 months post JCAR017 infusion)
- Total Exposure to JCAR017 as Measured by Area Under the Curve (AUC) of JCAR017 by qPCR(At baseline and up until 24 months post JCAR017 infusion)
- Percent of Participants With Presence of JCAR017 Transgene in Peripheral Blood by qPCR(At Day 29 and Months 2, 3, 6, 9, 12, 18, and 24 post JCAR017 infusion.)
- Change From Baseline in European Organisation for Research and Treatment of Cancer - Quality of Life C30 Questionnaire (EORTC QLQ-C30) Scores(At baseline and Day 1, 29, 60, 90, 180, 270, 365, 545, and 730 post JCAR017 infusion.)
- Change From Baseline in Functional Assessment of Cancer Treatment-Lymphoma "Additional Concerns" Subscale (FACT-LymS) Scores(At baseline and Day 1, 29, 60, 90, 180, 270, 365, 545, and 730 post JCAR017 infusion.)