A Phase 2 Multicenter Study of Axicabtagene Ciloleucel in Subjects With Relapsed/Refractory Indolent Non-Hodgkin Lymphoma (iNHL)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 159
- 试验地点
- 19
- 主要终点
- Objective Response Rate (ORR): Percentage of Participants With Objective Response Per the Lugano Classification by Central Assessment
研究概览
简要总结
The goal of this study is to assess whether axicabtagene ciloleucel improves the clinical outcome in participants with relapsed or refractory indolent non-Hodgkin lymphoma (r/r) iNHL.
详细描述
After completing at least 60 months (FL participants) or at least 24 months (MZL participants) of assessments in this study since the initial axicabtagene ciloleucel infusion and after agreement by the Sponsor, participants will transition to a long-term follow-up (LTFU) study, KT-US-982-5968 where they will complete the remainder of the 15 year follow-up assessments.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Individual has follicular lymphoma (FL) or marginal zone lymphoma (MZL) that has progressed after at least 2 lines of treatment with combination chemoimmunotherapy) (e.g. R-bendamustine, R-CHOP).
- •Individual has (measurable disease).
- •Individual has no known presence or history of central nervous system (CNS) involvement by lymphoma.
- •If individual is on conventional systemic therapy or systemic inhibitory/stimulatory immune checkpoint therapy, individual is able to stop conventional therapy 2 weeks or 5 half-lives, whichever is shorter, or immune checkpoint therapy 3 half-lives prior to planned leukapheresis.
- •Individual has Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 and adequate renal, hepatic, pulmonary, and cardiac function
- •Individual is not pregnant or breastfeeding (female individuals only) and is willing to use birth control from the time of consent through 12 months following chimeric antigen receptor (CAR) T cell infusion (both male and female individuals).
排除标准
- •Transformed FL or MZL
- •Small lymphocytic lymphoma
- •Histological Grade 3b FL
- •Individual will have undergone autologous transplant within 6 weeks of planned leukapheresis or has undergone allogeneic transplant.
- •Individual has evidence of involvement of the heart by lymphoma or requirement for urgent therapy due to ongoing or impending oncologic emergency (e.g. mass effect, tumor lysis syndrome, etc.)
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Axicabtagene Ciloleucel (Follicular Lymphoma)
Participants with relapsed or refractory (r/r) B-cell indolent non-Hodgkin lymphoma (iNHL) subtype of follicular lymphoma (FL) will receive the following treatment during the study:
- A conditioning chemotherapy regimen of fludarabine 30 mg/m^2/day and cyclophosphamide 500 mg/m^2/day for 3 days (Day -5 to Day -3).
- A single infusion at a target dose of 2×10^6 anti-cluster of differentiation 19 (CD19) chimeric antigen receptor (CAR) transduced autologous T cells/kg on Day 0.
干预措施: Axicabtagene ciloleucel (Biological)
Axicabtagene Ciloleucel (Follicular Lymphoma)
Participants with relapsed or refractory (r/r) B-cell indolent non-Hodgkin lymphoma (iNHL) subtype of follicular lymphoma (FL) will receive the following treatment during the study:
- A conditioning chemotherapy regimen of fludarabine 30 mg/m^2/day and cyclophosphamide 500 mg/m^2/day for 3 days (Day -5 to Day -3).
- A single infusion at a target dose of 2×10^6 anti-cluster of differentiation 19 (CD19) chimeric antigen receptor (CAR) transduced autologous T cells/kg on Day 0.
干预措施: Cyclophosphamide (Drug)
Axicabtagene Ciloleucel (Follicular Lymphoma)
Participants with relapsed or refractory (r/r) B-cell indolent non-Hodgkin lymphoma (iNHL) subtype of follicular lymphoma (FL) will receive the following treatment during the study:
- A conditioning chemotherapy regimen of fludarabine 30 mg/m^2/day and cyclophosphamide 500 mg/m^2/day for 3 days (Day -5 to Day -3).
- A single infusion at a target dose of 2×10^6 anti-cluster of differentiation 19 (CD19) chimeric antigen receptor (CAR) transduced autologous T cells/kg on Day 0.
干预措施: Fludarabine (Drug)
Axicabtagene Ciloleucel (Marginal Zone Lymphoma)
Participants with r/r B-cell iNHL subtype of marginal zone lymphoma (MZL) will receive the following treatment during the study:
- A conditioning chemotherapy regimen of fludarabine 30 mg/m^2/day and cyclophosphamide 500 mg/m^2/day IV for 3 days (Day -5 to Day -3).
- A single infusion at a target dose of 2×10^6 anti-CD19 CAR transduced autologous T cells/kg on Day 0.
干预措施: Axicabtagene ciloleucel (Biological)
Axicabtagene Ciloleucel (Marginal Zone Lymphoma)
Participants with r/r B-cell iNHL subtype of marginal zone lymphoma (MZL) will receive the following treatment during the study:
- A conditioning chemotherapy regimen of fludarabine 30 mg/m^2/day and cyclophosphamide 500 mg/m^2/day IV for 3 days (Day -5 to Day -3).
- A single infusion at a target dose of 2×10^6 anti-CD19 CAR transduced autologous T cells/kg on Day 0.
干预措施: Cyclophosphamide (Drug)
Axicabtagene Ciloleucel (Marginal Zone Lymphoma)
Participants with r/r B-cell iNHL subtype of marginal zone lymphoma (MZL) will receive the following treatment during the study:
- A conditioning chemotherapy regimen of fludarabine 30 mg/m^2/day and cyclophosphamide 500 mg/m^2/day IV for 3 days (Day -5 to Day -3).
- A single infusion at a target dose of 2×10^6 anti-CD19 CAR transduced autologous T cells/kg on Day 0.
干预措施: Fludarabine (Drug)
结局指标
主要结局
Objective Response Rate (ORR): Percentage of Participants With Objective Response Per the Lugano Classification by Central Assessment
时间窗: Up to 85.6 months
OR:CR (complete metabolic response (CMR)+complete radiological response (CRR))+PR (partial MR response (PMR) +partial RR(PRR)).CMR: score 1(no uptake above background)/2(uptake≤mediastinum)/3(uptake \>mediastinum but ≤liver)with/without a residual mass on positron emission tomography 5-point scale;no new lesions,CRR:target nodes/nodal masses regressed to ≤1.5 cm in longest transverse diameter of lesion (LDi);no extralymphatic sites of disease;absent non-measured lesion(NMLs);organ enlargement regress to normal; no new sites;bone marrow normal by morphology.PMR:score 4(uptake moderately\>liver)/5(uptake markedly\>liver, new lesions) with reduced uptake compared with baseline and residual mass;no new lesions;responding disease at interim/residual disease at end of treatment.PRR:≥50% decrease in sum of product of diameters up to 6 target nodes and extra-nodal sites;absent/normal,regressed,but no increase of NMLs;spleen regressed by\>50% in length beyond normal. Percentages were rounded-off.
次要结局
- ORR: Percentage of Participants With OR Per the Lugano Classification by Central Assessment Among Participants With 3 or More Lines of Prior Therapy(Up to 85.6 months)
- Percentage of Participants With CR Per the Lugano Classification by Central Assessment(Up to 85.6 months)
- Percentage of Participants With CR Per Lugano Classification by Central Assessment Among Participants With 3 or More Lines of Prior Therapy(Up to 85.6 months)
- ORR: Percentage of Participants With OR Per the Lugano Classification by Investigator Assessment(Up to 85.6 months)
- Percentage of Participants With Best Overall Response (BOR) Per the Lugano Classification by Central Assessment(Up to 85.6 months)
- Percentage of Participants With BOR Per the Lugano Classification by Investigator Assessment(Up to 85.6 months)
- Duration of Response (DOR) by Central Assessment(Up to 85.6 months)
- DOR by Investigator Assessment(Up to 85.6 months)
- Progression-free Survival (PFS) Per Lugano Classification by Central Assessment(Up to 85.6 months)
- PFS Per Lugano Classification by Investigator Assessment(Up to 85.6 months)
- Overall Survival (OS)(Up to 85.6)
- Time to Next Therapy(Up to 85.6 months)
- Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)(Up to 85.6 months)
- Percentage of Participants With Increase in Laboratory Values Reported as Grade 3 or Higher(Up to 85.6 months)
- Percentage of Participants With Decrease in Laboratory Values Reported as Grade 3 or Higher(Up to 85.6 months)
- Percentage of Participants With Antibodies Against Anti-CD19 Chimeric Antigen Receptor (CAR) T Cells(Up to 85.6 months)
- Levels of Anti-CD19 CAR T Cells in Blood(Day 7, Week 2, Week 4, Month 3, Month 6, Month 12, Month 18 and Month 24)
- Levels of Serum C-Reactive Protein (CRP)(Baseline (at enrollment), predose: Day 0, postdose: Day 3, Day 7, Week 2, Week 4)
- Levels of Serum Ferritin, Serum ICAM-1, Serum IL-2 R Alpha, Serum Perforin and Serum VCAM-1(Baseline (at enrollment), predose: Day 0, postdose: Day 3, Day 7, Week 2, Week 4)
- Levels of Serum CXCL10, Serum Granzyme B, Serum IFN-gamma, Serum IL-1 RA, Serum IL-2, Serum IL-6, Serum IL-7, Serum IL-8, Serum IL-10, Serum IL-15, Serum TNF Alpha(Baseline (at enrollment), predose: Day 0, postdose: Day 3, Day 7, Week 2, Week 4)