A Phase Ib, Multicenter Study to Determine the Safety and Tolerability of Tisagenlecleucel in Combination With Ibrutinib in Adult Patients With Relapsed and/or Refractory Diffuse Large B-cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Incidence of adverse events (AEs) and serious adverse events (SAEs)
研究概览
简要总结
A multi-center, open-label, phase Ib study to evaluate the safety and tolerability of the administration of tisagenlecleucel in combination with ibrutinib in patients with r/r DLBCL who have received two or more lines of systemic therapy, including an anti-CD20 and anthracycline based chemotherapy, and who have progressed after or are not candidates for ASCT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Parallel
- 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
- •Confirmed DLBCL as per the local histopathological assessment.
- •Relapsed or refractory disease having received 2 or more lines of systemic therapy, including anti-CD20 and anthracycline based chemotherapy, and either having progressed after (or relapsed after) ASCT, or being ineligible for or not consenting to ASCT.
- •Measurable disease at time of enrollment.
- •Eastern Cooperative Oncology Group (ECOG) performance status that is either 0 or 1 at screening.
- •Adequate renal, liver, and bone marrow, organ function, and minimum level of pulmonary reserve.
排除标准
- •Patients with Richter's transformation, Burkitt's lymphoma, and primary DLBCL of the CNS.
- •Prior anti-CD19 directed therapy.
- •Prior gene therapy.
- •Prior adoptive T cell therapy.
- •Prior ibrutinib therapy within the 30 days prior to screening.
- •Patients with active CNS involvement are excluded, except if the CNS involvement has been effectively treated and provided that local treatment was > 4 weeks before enrollment.
- •Prior allogeneic HSCT
- •. Significant cardiac abnormality including history of myocardial infarction within 6 months prior to screening as detailed in the study protocol.
- •Other eligibility criteria may apply.
研究组 & 干预措施
Ibrutinib (after leukapheresis) + Tisagenlecleucel
Patients will start ibrutinib treatment after leukapheresis.
干预措施: Tisagenlecleucel (Biological)
Ibrutinib (before leukapheresis) + Tisagenlecleucel
Patients will start ibrutinib treatment before leukapheresis
干预措施: Tisagenlecleucel (Biological)
Ibrutinib (before leukapheresis) + Tisagenlecleucel
Patients will start ibrutinib treatment before leukapheresis
干预措施: Ibrutinib (Drug)
Ibrutinib (after leukapheresis) + Tisagenlecleucel
Patients will start ibrutinib treatment after leukapheresis.
干预措施: Ibrutinib (Drug)
结局指标
主要结局
Incidence of adverse events (AEs) and serious adverse events (SAEs)
时间窗: 24 months
Month 24 is planned study end
Severity of adverse events (AEs) and serious adverse events (SAEs)
时间窗: 24 months
Month 24 is planned study end
Ibrutinib dose modification following tisagenlecleucel infusion
时间窗: 24 months
Month 24 is planned study end
次要结局
- Progression Free Survival (PFS)(24 months)
- Cellular kinetics of Tisagenlecleucel (Tmax)(24 months)
- Cellular kinetics of Tisagenlecleucel (AUC)(24 months)
- Cellular kinetics of Tisagenlecleucel (Tlast)(24 month)
- Response Rate(Month 6)
- Duration of Response(24 months)
- Cellular kinetics of Tisagenlecleucel (Clast)(24 month)
- Tisagenlecleucel transgene concentrations(24 months)
- Characterize efficacy of tisagenlecleucel in the presence of ADA and/or anti-tisagenlecleucel t-cell response(24 month)
- Overall Response Rate(24 months)
- Overall Survival (OS)(24 months)
- Cellular kinetics of Tisagenlecleucel (Cmax)(24 months)
- Anti-drug antibody (ADA) response to Tisagenlecleucel (humoral immunogenicity)(24 months)
- Anti- tisagenlecleucel t-cell response (cellular immunogenicity)(24 months)
- Characterize cellular kinetic parameters in the presence of ADA and/or anti-tisagenlecleucel t-cell response(24 months)