A Safety Trial of Lisocabtagene Maraleucel (JCAR017) for Relapsed and Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL) in the Outpatient Setting
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 104
- 试验地点
- 23
- 主要终点
- Percentage of Participants With Cytokine Release Syndrome (CRS) Adverse Events Grade ≥ 3
研究概览
简要总结
This is an open-label, multicenter, Phase 2 study to determine the safety, PK, and efficacy of lisocabtagene maraleucel (JCAR017) in subjects who have relapsed from, or are refractory to, two lines of immunochemotherapy for aggressive B-cell non-Hodgkin lymphoma (NHL) in the outpatient setting. Subjects will receive treatment with JCAR017 and will be followed for up to 2 years.
详细描述
This is an open-label, multicenter, Phase 2 study to assess the safety and antitumor activity in adult patients with relapsed or refractory B-cell non-Hodgkin Lymphoma when administered with lisocabtagene maraleucel (JCAR017) in the outpatient setting.
Upon the successful product generation of lisocabtagene maraleucel, subjects will enter the treatment phase of the study. Treatment will include lymphodepleting chemotherapy followed by lisocabtagene maraleucel administration. Subjects will then enter the post-treatment follow-up phase of the study and will be followed for approximately 24 months for safety, disease status, health-related quality of life (HRQoL), and survival. Long-term follow-up will continue under a separate long-term follow-up protocol, per health regulatory authority guidelines, currently up to 15 years after the last lisocabtagene maraleucel administration.
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
- •Age ≥ 18 years at the time of consent
- •Relapsed or refractory B-cell NHL of the following histologies: diffuse large B cell lymphoma (DLBCL) not otherwise specified; includes biopsy-confirmed transformed DLBCL from indolent histologies, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology, primary mediastinal B-cell lymphoma(PMBCL), and follicular lymphoma Grade 3B. Subjects must have been treated with an anthracycline and rituximab (or other CD20-targeted agent) and have relapsed or refractory disease after at least 2 systemic lines of therapy for DLBCL or after auto-HSCT.
- •Positron-emission tomography-positive disease by Lugano Classification
- •Eastern Cooperative Oncology Group performance status of 0 to 1
- •Adequate bone marrow, renal, hepatic, pulmonary, cardiac organ function
- •Adequate vascular access for leukapheresis procedure
- •Subjects who have received previous CD19-targeted therapy must have CD19-positive lymphoma confirmed on a biopsy since completing the prior CD19-targeted therapy
- •Subjects must agree to use appropriate contraception.
排除标准
- •Subjects with central nervous system (CNS)-only involvement by malignancy (note: subjects with secondary CNS involvement are allowed on study)
- •History of prior allogeneic hematopoietic stem cell transplant
- •Treatment with alemtuzumab within 6 months of leukapheresis, or treatment with fludarabine or cladribine within 3 months of leukapheresis
- •History of another primary malignancy that has not been in remission for at least 2 years.The following are examples of exceptions from the 2-year limit: nonmelanoma skin cancer, definitively-treated stage 1 solid tumor with a low risk of recurrence, curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on a Papanicolau smear.
- •Active hepatitis B or hepatitis C infection at the time of screening
- •History of or active human immunodeficiency virus infection at the time of screening
- •Uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate anti-infection treatment at the time of leukapheresis or lisocabtagene maraleucel administration
- •Presence of acute or chronic graft-versus-host disease
- •History of clinically significant cardiac conditions within the past 6 months
- •History or presence of clinically relevant CNS pathology such as epilepsy/seizure, paresis, aphasia, stroke, cerebral edema, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
- •Pregnant or nursing women
- •Subject does not meet protocol-specified washout periods for certain prior treatments
- •Prior CAR T-cell or other genetically modified T-cell therapy
- •Progressive vascular tumor invasion, thrombosis, or embolism
- •Venous thrombosis or embolism not managed on stable regimen of anticoagulation
- •Uncontrolled medical, psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol; or unwillingness or inability to follow the procedures required in the protocol
研究组 & 干预措施
Lisocabtagene maraleucel
Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of lisocabtagene maraleucel. During lisocabtagene maraleucel production, subjects may receive low-dose chemotherapy for disease control. Upon successful generation of lisocabtagene maraleucel product, subjects will receive treatment which will include lymphodepleting chemotherapy followed by one dose of lisocabtagene maraleucel administered by intravenous (IV) injection.
干预措施: lisocabtagene maraleucel (Biological)
结局指标
主要结局
Percentage of Participants With Cytokine Release Syndrome (CRS) Adverse Events Grade ≥ 3
时间窗: From first dose to 90 days following first dose (up to approximately 90 days)
Cytokine release syndrome is characterized by high fever, fatigue, nausea, headache, dyspnea, tachycardia, rigors, hypotension, hypoxia, myalgia/arthralgia, and anorexia. Incidence of Grade ≥ 3 CRS, based on the TEAE with MedDRA PT "Cytokine release syndrome," graded according to the grading scale adapted from Lee (Lee 2014).
Percentage of Participants With Neurotoxicity (NT) Adverse Events Grade ≥ 3
时间窗: From first dose to 90 days following first dose (up to approximately 90 days)
NT events have also been reported and may include neurologic symptoms such as altered mental status, aphasia, altered level of consciousness, and seizures or seizure-like activity. Incidence of Grade ≥ 3 NT, defined as an Investigator-identified TEAE considered neurotoxicity related to JCAR017.
Percentage of Participants With Infection Adverse Events Grade ≥ 3
时间窗: From first dose to 90 days following first dose (up to approximately 90 days)
Incidence of treatment-emergent Grade ≥ 3 infections, defined using MedDRA SOC.
Percentage of Participants With Grade ≥ 3 Prolonged Cytopenia at Day 29.
时间窗: At Day 29 after first treatment
Prolonged cytopenia is defined as the occurrence of Grade ≥ 3 cytopenia not resolved by the Day 29 visit, based on laboratory results of low hemoglobin, absolute neutrophil count decreased, and platelet count decreased. The frequency of subjects experiencing each individual laboratory abnormality and the total number with at least 1 abnormality will be summarized, as will recovery from prolonged cytopenia after Day 29.
次要结局
- Number of Participants With Adverse Events(From first dose to 90 days following first dose (up to approximately 90 days))
- Number of Participants With Clinically Significant Laboratory Abnormalities- Hematology(From first dose to up to 41 months)
- Number of Participants With Clinically Significant Laboratory Abnormalities- Chemistry(From first dose to up to 41 months)
- Number of Participants With Adverse Events Grade ≥ 3(From first dose to 90 days following first dose (up to approximately 90 days))
- Time to Onset and Time to Resolution of Grade ≥ 3 Cytokine Release Syndrome (CRS)(From first dose to up to approximately 41 months)
- Time to Onset and Time to Resolution of Grade ≥ 3 Neurotoxicity (NT)(From first dose to up to approximately 41 months)
- Number of Participants Administered Tocilizumab and Corticosteroid for Management of Cytokine Release Syndrome (CRS)(From first dose to up to approximately 41 months)
- Number of Participants Administered Tocilizumab and Corticosteroid for Management of Neurotoxicity (NT)(From first dose to up to study completion (Approximately 57 Months and 24 days))
- Objective Response Rate (ORR)(From first dose to up to approximately 41 months)
- Overall Survival (OS)(From first dose to up to study completion (Approximately 57 Months and 24 days))
- Mean Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30(From Enrollment to end of follow up, approximately 26 months)
- Number of Intensive Care Unit (ICU) Inpatient Days and Non-ICU Inpatient Days and Reasons for Hospitalization(From first hospitalization to the last. Approximately 31 days)
- Number of Participants Who Received Transfusions(From first dose to end of treatment period approximately 24 months)
- Complete Response Rate (CRR)(From first dose to up to approximately 41 months)
- Area Under the Blood Concentration-time Curve From Time to Zero to 28 Days After Dosing AUC (0-28)(28days after first dose)
- Duration of Response (DoR) and Duration of Complete Response (DoCR)(From first dose to up to approximately 41 months)
- Progression Free Survival (PFS)(From first dose to up to study completion (Approximately 57 Months and 24 days))
- Maximum Observed Blood Concentration (Cmax)(28days after first dose)
- Time of Maximum Observed Blood Concentration (Tmax)(28days after first dose)
- Mean Change From Baseline in EuroQol Instrument EQ-5D-5L.(Post Dose Month 24)
- Number of Participants Requiring Growth Factor Support.(From first dose to end of treatment period approximately 24 months)
- Number of Participants Requiring Intravenous Immunoglobulin (IVIG) Support(From first dose to end of treatment period approximately 24 months)