COBALT: Evaluation of CAR19 T-cells as an Optimal Bridge to Allogeneic Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Feasibility of adequate leucapheresis collection and generation of CAR19 T cells.
研究概览
简要总结
The purpose of this study is to administer novel cluster of differentiation antigen 19 (CD19) specific Chimeric Antigen Receptor T-cells (CAR19 T-cells) to patients with relapsed or resistant Diffuse Large B Cell Lymphoma (DLBCL) to assess the safety and efficacy of this strategy as a bridge to allogeneic transplantation.
详细描述
Patients with Diffuse Large B Cell Lymphoma (DLBCL) resistant to or relapsing following rituximab-containing chemotherapy regimens have a poor prognosis. Patients may receive salvage chemotherapy and possibly an autologous stem cell transplant (auto-SCT). A proportion of these patients, however, will not respond to the chemotherapy or may relapse after the auto-SCT and therefore require novel treatment options. Such patients may benefit from an allogeneic stem cell transplantation (allo-STC).
In this study the investigators aim to administer CAR19 T-cells to act as a bridge to the transplant strategy. Specifically, (1) the feasibility of generating CD19 specific Chimeric Antigen Receptor T-cells called CAR19 T-cells, (2) the safety of administering the CD19 CAR T-cells in this setting, (3) how well the CAR19 T-cells engraft and (4) to evaluate how effective these cells are as a bridge to allogeneic transplantation.
Following informed consent and registration to the trial, patients will undergo an unstimulated leucapheresis for generation of the CAR19 T cells. Whilst the cells are being generated, patients will proceed with a further cycle of standard salvage (recommended ifosfamide, epirubicin and etoposide (i.e. the IVE regime), and should not receive rituximab. Patients will receive pre-conditioning with intravenous fludarabine and cyclophosphamide prior to infusion of a single dose of CAR-modified T-cells. An escalating dose protocol will be employed to identify a minimum effective dose of CAR19 T-cells.
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
- 16 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 16-65 years
- •Confirmed diagnosis of CD19+ DLBCL
- •Primary resistant or relapsed disease failing to achieve metabolic Complete Response (CR) to 1st line salvage, or relapse post autograft failing to achieve metabolic CR following a single further cycle of salvage
- •Potential allogeneic transplant candidate
- •Agreement to have a pregnancy test, use adequate contraception for 12 months post-CAR19 T-cell infusion
- •Karnofsky performance status >60
- •Written informed consent
排除标准
- •Women who are pregnant or lactating
- •Prior allogeneic transplantation
- •Progressive disease following most recent salvage prior to planned leucapheresis (those with mixed response are eligible)
- •Prior history of ischaemic heart disease, dysrhythmias, abnormal electrocardiogram (ECG)(Left Bundle Branch Block (LBBB)), Multiple Gated Acquisition (MUGA) left ventricular ejection fraction (LVEF) <40%
- •Exclusions for proceeding to allogeneic transplantation (active hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV); liver function test (LFT) >3 x upper limit of normal (ULN); Creatinine Clearance (CrCl) <40 ml/min; or other comorbidity that precludes transplantation)
- •Known central nervous system (CNS) involvement or cerebral vascular accident (CVA) within prior 3 months
- •Patients receiving corticosteroids at a dose of > 10mg prednisolone per day (or equivalent)
- •Use of rituximab within the last 2 months prior to CAR19 T-cell infusion
- •Active autoimmune disease requiring immunosuppression
- •Life expectancy <3 months
- •Known allergy to albumin or dimethylsulfoxide (DMSO)
- •Any contraindication to the administration and use of ifosfamide, epirubicin, etoposide, fludarabine and cyclophosphamide.
研究组 & 干预措施
CAR19 T-cells
Patients will receive a single infusion of CAR19 T-cells following standard pre-conditioning with cyclophosphamide and fludarabine.
The CAR19 T-cells are to be administered on day 0.
干预措施: Leukapheresis (Procedure)
CAR19 T-cells
Patients will receive a single infusion of CAR19 T-cells following standard pre-conditioning with cyclophosphamide and fludarabine.
The CAR19 T-cells are to be administered on day 0.
干预措施: Cyclophosphamide (Drug)
CAR19 T-cells
Patients will receive a single infusion of CAR19 T-cells following standard pre-conditioning with cyclophosphamide and fludarabine.
The CAR19 T-cells are to be administered on day 0.
干预措施: Fludarabine (Drug)
CAR19 T-cells
Patients will receive a single infusion of CAR19 T-cells following standard pre-conditioning with cyclophosphamide and fludarabine.
The CAR19 T-cells are to be administered on day 0.
干预措施: CAR19 T-Cells (Biological)
结局指标
主要结局
Feasibility of adequate leucapheresis collection and generation of CAR19 T cells.
时间窗: 1 month
The number of CAR19 T cells successfully manufactured as a fraction of the number of patients undergoing leukapheresis (all patients registered).
Toxicity evaluation following CAR19 T-cell administration.
时间窗: 1 year
Toxicity will be examined for each patient receiving CAR19 T cells, using the maximum grade for each toxicity type, all summarized as number of patients with adverse events.
Efficacy of CAR19 T-cells.
时间窗: 1 year
Efficacy will be defined as the number of patients that meet the clinical complete responders criteria.
次要结局
- CAR19 T-cell engraftment(1 year)
- B cell compartment(1 year)
- Eligibility to allogeneic transplantation(1-3 years)
- Cytokine profile(1 year)
- Clinical complete response(1 month)