Chimeric Antigen Receptor (CAR)19 Donor Lymphocytes for Relapsed Cluster of Differentiation (CD)19+ Malignancies Following Allogeneic Transplantation (CARD)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Maximum grade for each toxicity type as assessed by CTCAE v4.03, summarized as proportions.
研究概览
简要总结
Eligible patients will receive escalating doses of 4G7-CARD T-cells paralleling clinical standard of care with unmanipulated donor lymphocytes. There are 3 intra-patient dose levels planned.
Patients will be followed up regularly during the interventional phase of the study until 12 months post-final 4G7-CARD T-cell infusion. Thereafter patients will be followed up annually for years 2 and 3.
详细描述
Patients will receive escalating doses of 4G7-CARD T-cells (after pre-conditioning with Fludarabine and Cyclophosphamide), paralleling clinical standard of care with unmanipulated donor lymphocytes. Intra-patient dose escalation will proceed at intervals of not less than 8 weeks, dependent on development of toxicity or evidence of efficacy and confirmation by the Trial Management Group.
Three dose cohorts levels are planned, and dosing will be according to total CD3+ T- cell dose as this correlates with toxicity in the unmanipualated donor lymphocyte setting:
- Dose Level 1: 1x10^6 CD3+ T-cells/kg (starting dose for all patients)
- Dose Level 2: 3x10^6 CD3+ T-cells/kg
- Dose Level 3: 1x10^7 CD3+ T-cells/kg
The inter-patient dosing for the first 3 patients was at least 28 days, following TMG confirmation.
Patients will be followed up regularly during the interventional phase of the study until 12 months post-final 4G7-CARD T-cell infusion. During the long term follow up phase of the study (years 2-3 post-final 4G7-CARD T-cell infusion) patients will be followed-up annually for overall survival, disease status and safety.
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 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 16-70 years
- •Confirmed diagnosis of CD19+ malignancy relapsing following allogeneic transplantation
- •Agreement to have a pregnancy test, use adequate contraception for 12 months post-final 4G7-CARD T-cell infusion
- •Karnofsky performance status >60
- •Written informed consent
排除标准
- •Women who are pregnant or lactating
- •Prior history of ischaemic heart disease, dysrhythmias, abnormal ECG (LBBB), Multi Gated Acquisition Scan (MUGA) left ventricular ejection fraction (LVEF<40%) (if performed)
- •Known involvement of the central nervous system or cerebral vascular accident within prior 3 months
- •Patients receiving corticosteroids at a dose of > 10mg prednisolone per day (or equivalent)
- •Active graft versus host disease requiring immunosuppression
- •Use of rituximab within the last 2 months prior to ATIMP infusion
- •Known allergy to albumin or dimethyl sulfoxide (DMSO)
- •Patients who have experienced significant neurotoxicity following blinatumomab treatment
结局指标
主要结局
Maximum grade for each toxicity type as assessed by CTCAE v4.03, summarized as proportions.
时间窗: Up to 3 years post final 4G7-CARD T-cell infusion
Toxicity evaluation following 4G7-CARD T-cell administration as evaluated by the occurrence of adverse events per studied dose using CTCAE v4.03, defined as \>grade 2 events that are causally related to study treatment or procedure or Serious Adverse Reactions that require withdrawal of the patient from the study; development and severity of graft-versus-host-disease (GvHD) following cell infusion will also be evaluated as a potential toxicity, as well as development and severity of cytokine release syndrome / macrophage activation syndromes assessed by 'University of Pennsylvania' criteria
Feasibility of generation of 4G7-CARD T-cells using the ProdigyTM system
时间窗: Through patient registration and manufacturing period, an average of 18 months from start of trial
The number of ATIMP successfully manufactured would be assessed for all registered patients
次要结局
- Assessing the timing and magnitude of cytokine release, evaluated using Cytokine bead arrays(Sampling occurs at days 0, 4, 6, 11, 18, plus 1 month post final 4G7-CARD T-cell infusion)
- Assessment of engraftment, expansion and persistence of the 4G7-CARD T-cells as determined by quantitative polymerase chain reaction (qPCR) or flow cytometry(Sampling occurs at days 0, 4, 6, 11, 18, plus months 1, 2, 3, 6, 9 and 1 year post final 4G7-CARD T-cell infusion)
- Assessing the depletion of B cell compartment, as determined by flow cytometry(Sampling occurs at days 0, 4, 6, 11, 18, plus months 1, 2, 3, 6, 9 and 1 year post final 4G7-CARD T-cell infusion)