A Phase II, Single Arm, Multicenter Open Label Trial to Determine the Efficacy and Safety of Tisagenlecleucel (CTL019) in Adult Patients With Refractory or Relapsed Follicular Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 98
- 试验地点
- 37
- 主要终点
- Complete Response Rate (CRR) Per Independent Review Committee (IRC) Assessment
研究概览
简要总结
This is a multi-center, phase II study to determine the efficacy and safety of tisagenlecleucel in adult patients with relapsed or refractory FL.
详细描述
This single-arm, open label study had the following sequential phases: Screening, Pretreatment, Treatment and Follow-up. In the Pre-treatment phase, the patient could undergo bridging therapy (optional) and lymphodepleting (LD) chemotherapy. Treatment and Follow-up Phase included tisagenlecleucel infusion, and safety and efficacy follow-up for at least 24 months. For all the patients who received tisagenlecleucel infusion, additional survival follow-up was to be performed to determine survival status every 3 months.
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Refractory or relapsed Follicular Lymphoma (Grade 1, 2, 3A)
- •Radiographically measurable disease at screening
排除标准
- •Evidence of histologic transformation
- •Follicular Lymphoma Grade 3B
- •Prior anti-CD19 therapy
- •Prior gene therapy
- •Prior adoptive T cell therapy
- •Prior allogeneic hematopoietic stem cell transplant
- •Active CNS involvement by malignancy
- •Other protocol-defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
CTL019
All patients who received tisagenlecleucel infusion.
干预措施: tisagenlecleucel (Biological)
结局指标
主要结局
Complete Response Rate (CRR) Per Independent Review Committee (IRC) Assessment
时间窗: 1 year
Complete response rate was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) recorded from tisagenlecleucel infusion until progressive disease or start of new anticancer therapy, whichever came first. CRR was determined by an independent review committee (IRC) and was based on Lugano 2014 classification response criteria. The radiological response is first obtained from CT and PET studies according to the Lugano 2014 criteria. CT response is based on anatomical measurements of index/non-index/new lesions and spleen length. The possible response outcomes are complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). PET response based on a 5-point scale (5PS) or Deauville score. The possible outcomes for PET response are complete metabolic response (CMR), partial metabolic response (PMR), no metabolic response (NMR), or progressive metabolic disease (PMD).
次要结局
- Humoral Immunogenicity(2 years)
- AUC0-84d; Cellular Kinetic Parameter of Tisagenlecleucel(2 years)
- Overall Response Rate (ORR) Per IRC Assessment(1 year)
- Tisagenlecleucel Transgene Concentration(2 years)
- Tmax; Cellular Kinetic Parameter of Tisagenlecleucel(2 years)
- T1/2; Cellular Kinetic Parameter of Tisagenlecleucel(2 years)
- Summary Scores of PRO Measured by FACT-Lym Quality of Life Questionnaire(2 years)
- Tlast; Cellular Kinetic Parameter of Tisagenlecleucel(2 years)
- Progression Free Survival (PFS)(2 years)
- Summary Scores of PRO Measured by EQ-5D-3L Quality of Life Questionnaire(2 years)
- Duration of Response (DOR) Per IRC(1 year)
- Overall Survival (OS)(2 years)
- Cmax; Cellular Kinetic Parameter of Tisagenlecleucel(2 years)
- AUC0-28; Cellular Kinetic Parameter of Tisagenlecleucel(2 years)
- Summary of Exposure of CD3+ Tisagenlecleucel Cells in Peripheral Blood(2 years)
- Summary Scores of PRO Measured by SF-36v2 Quality of Life Questionnaire(2 years)
- Cellular Immunogenicity(2 years)
- Duration of Response (DOR) Per IRC Assessment(approx. 60 months)
- Duration of Response (DOR) for Complete Response (CR) Only Per IRC Assessment(approx. 60 months)
- Progression Free Survival (PFS) Per IRC Assessment(up to 61.7 months)
- Overall Survival (OS)(up to 65.8 months)
- Tisagenlecleucel Transgene Concentration Levels as Measured by Quantitative Polymerase Chain Reaction (qPCR) Method, by Clinical Response Per IRC Assessment(Month 60 (peripheral blood), Month 6 (bone marrow))
- Cmax; Cellular Kinetic Parameter of Tisagenlecleucel Transgene Levels by qPCR, Based on Clinical Response IRC Assessment(up to 60 months after infusion)
- Tmax; Cellular Kinetic Parameter of Tisagenlecleucel Transgene Levels by qPCR, Based on Clinical Response by IRC Assessment(up to 60 months after infusion)
- AUC0-28d and AUC0-84d; Cellular Kinetic Parameter of Tisagenlecleucel Transgene Levels by qPCR, Based on Clinical Response by IRC Assessment(0 to 28 days after infusion, 0 to 84 days after infusion)
- AUC0-28d and AUC0-84d; Cellular Kinetic Parameter for Tisagenlecleucel by Flow Cytometry, Based on Clinical Response by IRC Assessment(AUC0-28d: from time of infusion to 28 days post-dose; AUC0-84d: from time of infusion to 84 days post-infusion)
- Cmax; Cellular Kinetic Parameter for Tisagenlecleucel by Flow Cytometry, Based on Clinical Response by IRC Assessment(From pre-dose until 60 months after infusion)
- Summary of Exposure of CD3+ Tisagenlecleucel Cells in Peripheral Blood for Tmax(From pre-dose until 60 months after infusion)
- Humoral Immunogenicity: Number of Participants With Anti-mCAR19 Antibodies, Per IRC Assessment(at any time post-baseline, up to 24 months post-infusion)
- Cellular Immunogenicity: Percentage of Interferon Gamma (IFNg+) Cells by Flow Cytometry Per IRC Assessment(pre-infusion (pre-Lymph depletion evaluation), 24 months post-infusion)
- Summary Scores of Patient-reported Outcome (PRO) Measured by SF-36v2 Quality of Life Questionnaire by Visit(Baseline (BL) Month (M) 3, M3, M6, M9, M12, M18, M24)
- Summary Scores of PRO Measured by SF-36v2 Quality of Life Questionnaire Reported by Change From Baseline(Change from baseline (CFB) M3, CFB M6, CFB M9, CFB M12, CFB M18, CFB M24)
- Health Status Measured by EQ-5D-3L Questionnaire(Baseline (BL), Month 3, Month 6, Month 9, Month 12, Month 18, Month 24, Month 36)
- Summary Scores of PRO Measured by EQ-VAS Quality of Life Questionnaire by Visit(Baseline (BL) Month (M) 3, M6, M9, M12, M18, M24, M36)
- Summary Scores of PRO Measured by EQ-VAS Quality of Life Questionnaire Reported by Change From Baseline(Baseline (BL), M3 change from baseline (CFB), M6 CFB, M9 CFB, M12 CFB, M18 CFB, M24 CFB, M36 CFB)
- Summary Scores of PRO Measured by FACT-Lym Quality of Life Questionnaire(Baseline (BL) Month (M) 3, M6, M9, M12, M18, M24, M36)
- Summary Scores of PRO Measured by FACT-Lym Quality of Life Questionnaire Reported by Change From Baseline(Baseline (BL), M3 change from baseline (CFB), M6 CFB, M9 CFB, M12 CFB, M18 CFB, M24 CFB, M36 CFB)