RadiothErapy priMIng for CAR-T
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 6
- 试验地点
- 3
- 主要终点
- Percentage of patients starting lymphodepletion on the planned start date without delay
研究概览
简要总结
The REMIT trial will investigate radiotherapy as a preferred bridging method prior to Tisagenlecleucel infusion in patients with relapsed or refractory Diffuse Large B Cell Lymphoma
详细描述
The REMIT Trial is an open label, single arm phase IIa study investigating Radiotherapy as preferred bridging method prior to Tisagenlecleucel treatment in patients with relapsed or refractory Diffuse Large B Cell Lymphoma approved to receive CD19 CAR-T cells as per their licensed indication.
The trial will recruit 20 patients who have been approved to receive Tisagenlecleucel treatment and where the tumour is amendable to radiotherapy as per standard of care.
Trial subjects (patients) during a 14 day screening phase will have their metabolic tumour burden assessed by PET-CT and bridging radiotherapy will be planned. Bridging radiotherapy will commence immediately after leukapheresis with dose adjustments according to disease burden and localisation.
Disease areas requiring effective long-term control will receive full dose radiotherapy, 20 - 30Gy /5-15# and other areas will receive low dose radiotherapy, 4Gy / 2# for optimal tumour debulking and priming effects.
Standard lymphodepletion will be given day -5 to day -3 followed by Tisagenlecleucel infusion on day 0. A window of 14-21 days will be left from last dose of radiotherapy and day 0.
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
- •Written informed consent
- •Age ≥ 18 years
- •Histologically proven DLBCL, including transformed follicular or marginal zone lymphoma
- •Measurable disease on cross-sectional imaging that is at least 1.5cm in the longest diameter and measurable in two perpendicular dimensions
- •Relapsed/refractory after 2 or more standard immuno-chemotherapies
- •Approved to receive Tisagenlecleucel as per the licenced indication
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Disease accessible for repeat biopsies (Selected patients only)
- •Disease amenable to radiotherapy as assessed by the treating clinical oncologist
- •Willing and able to comply with the requirements of the protocol, including contraceptive advice as per the protocol
排除标准
- •Prior radiotherapy at location/dose that would interfere with application of radiotherapy or outcome measures in this trial
- •Women who are pregnant or breast feeding
- •Previous therapy with any genetically modified autologous or allogeneic T-cell immunotherapy, unless treated with doses of genetically modified autologous or allogeneic T-cell immunotherapy within an abandoned dosing cohort in a first in human dose-escalation phase I clinical trial
结局指标
主要结局
Percentage of patients starting lymphodepletion on the planned start date without delay
时间窗: From planned start date of lymphodepletion until actual start date of lymphodepletion, assessed up to 2 weeks
To evaluate whether there is any delay in patients starting lymphodepletion
次要结局
- Overall response rate at 3 months and 6 months after Tisagenlecleucel infusion(At 3 and 6 months after Tisagenlecleucel infusion)
- Complete metabolic response at 3 months and 6 months after Tisagenlecleucel infusion(At 3 and 6 months after Tisagenlecleucel infusion)
- Median event-free survival and event-free survival at 12 months(12 months after Tisagenlecleucel infusion)
- Treatment emergent adverse events(From start of Tisagenlecleucel infusion until 30 days post Tisagenlecleucel infusion)
- Best overall response after Tisagenlecleucel infusion as per International Working Group 2014 criteria(After Tisagenlecleucel infusion through to study completion, an average of 24 months)
- Duration of response(From initial response until the date of first documented disease progression, assessed up to 24 months)
- Median progression free survival and progression free survival at 12 months(12 months after Tisagenlecleucel infusion)
- Median overall survival and overall survival at 12 months(12 months after Tisagenlecleucel infusion)
- Incidence of grade 3 or higher cytokine release syndrome and immune effector cell associated neurotoxicity syndrome(From start of Tisagenlecleucel infusion through to study completion, an average of 24 months)
- Neutrophil levels at 1, 3, 6 months after Tisagenlecleucel infusion(At 1, 3 and 6 months after Tisagenlecleucel infusion)
- Platelet levels at 1, 3, 6 months after Tisagenlecleucel infusion(At 1, 3 and 6 months after Tisagenlecleucel infusion)