A Randomized, Open-label, Multi-center Phase III Trial Comparing Tisagenlecleucel to Standard of Care in Adult Participants With Relapsed or Refractory Follicular Lymphoma (FL)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 109
- 试验地点
- 33
- 主要终点
- Progression-free survival (PFS) determined by blinded independent review committee (BIRC)
研究概览
简要总结
This trial will compare tisagenlecleucel to standard of care in adult participants with relapsed or refractory (r/r) follicular lymphoma.
详细描述
The purpose of this phase III study is to verify the clinical benefit of tisagenlecleucel for the treatment of r/r FL by comparing the tisagenlecleucel treatment strategy to standard of care therapy in patients with r/r FL after two or more lines of systemic therapy, with progression-free survival (PFS) as the primary endpoint.
The primary objective is to demonstrate superiority of the tisagenlecleucel treatment strategy over standard of care (SOC) therapy with respect to progression-free survival (PFS) determined by blinded independent review committee (BIRC) based on the Lugano response criteria.
Participants randomized to Arm A (tisagenlecleucel treatment) will receive a single infusion of 0.6 to 6 x 10^8 CAR-positive viable T-cells.
Participants randomized to Arm B (Standard of Care) will receive R2 or R-CHOP based on investigator choice and this has to be determined prior to randomization.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Age ≥ 18 years at the date of signing the informed consent form.
- •Follicular lymphoma grade 1, 2, or 3A confirmed histologically after latest relapse (local assessment).
- •Relapsed or refractory disease after a second or later line of systemic therapy including an anti-CD20 antibody and an alkylating agent.
- •Disease that is both active on Positron emission tomography (PET) scan (defined as a score of 4 or 5 on the Deauville 5-point scale) and measurable on Computed tomography (CT) scan.
- •ECOG performance status of 0, 1 or 2 at screening.
- •Adequate hematologic, renal, hepatic and pulmonary organ function at screening.
- •Must meet the institutional criteria to undergo leukapheresis (unless historical leukapheresis is available).
- •Must be eligible for treatment with the selected standard of care regimen.
排除标准
- •Follicular lymphoma grade 3B or evidence of histologic transformation.
- •Prior treatment with anti-CD19 therapy, gene therapy, or adoptive T-cell therapy.
- •Active CNS involvement by malignancy.
- •Clinically significant active infection, presence of Human immunodeficiency virus (HIV) antibody or active hepatitis B or C.
- •Active neurological autoimmune or inflammatory disorders (e.g., Guillain-Barré syndrome).
- •Investigational medicinal product within the last 30 days or five half-lives (whichever is longer) prior to randomization.
- •Clinically significant cardiovascular conditions such as acute coronary syndrome, significant cardiac arrhythmias, heart failure or decreased LVEF.
- •Other protocol defined inclusion/exclusion criteria may apply
研究组 & 干预措施
R2 or R-CHOP
Participants randomized to Standard of Care treatment will receive either R2 or R-CHOP based on investigator choice of therapies, and this has to be determined prior to randomization.
干预措施: Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone or prednisolone (R-CHOP) in 21-day cycles for 6 to 8 cycles (Drug)
Tisagenlecleucel
Participants randomized to the tisagenlecleucel treatment strategy will receive a single infusion of 0.6 to 6 x 10^8 CAR-positive viable T-cells
干预措施: Corticosteroids and/or Radiation (Bridging therapy) (Other)
R2 or R-CHOP
Participants randomized to Standard of Care treatment will receive either R2 or R-CHOP based on investigator choice of therapies, and this has to be determined prior to randomization.
干预措施: Lenalidomide and rituximab (R2) in 28-day cycles for up to 12 cycles. (Drug)
Tisagenlecleucel
Participants randomized to the tisagenlecleucel treatment strategy will receive a single infusion of 0.6 to 6 x 10^8 CAR-positive viable T-cells
干预措施: Lymphodepleting chemotherapy (Drug)
Tisagenlecleucel
Participants randomized to the tisagenlecleucel treatment strategy will receive a single infusion of 0.6 to 6 x 10^8 CAR-positive viable T-cells
干预措施: Tisagenlecleucel (Biological)
结局指标
主要结局
Progression-free survival (PFS) determined by blinded independent review committee (BIRC)
时间窗: 5 years
Progression free survival (PFS) based on Lugano response criteria, defined as time from randomization to the first of the following events to occur: * progressive disease (by BIRC) * death from any cause
次要结局
- Complete response rate (CRR) as assessed by BIRC (Key Secondary)(5 years)
- Complete response rate (CRR) as assessed by BIRC (Key Secondary)(5 years)
- Overall response rate (ORR) by BIRC(5 years)
- Overall survival (OS)(5 years)
- Time to next anti-lymphoma treatment (TTNT)(5 years)
- Duration of Response (DOR)(5 years)
- Pre-existing (prior to treatment) and treatment-induced anti-mCAR antibodies (humoral immunogenicity)(5 years)
- CAR transgene levels, as measured by quantitative polymerase chain reaction (qPCR), in peripheral blood, bone marrow (and other tissues, if available)(5 years)
- Replication competent lentivirus (RCL) by VSV-g qPCR in participants receiving tisagenlecleucel(5 years)