A Phase 2 Multicenter Study Evaluating the Efficacy of KTE-X19 in Subjects With Relapsed/Refractory Mantle Cell Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 105
- 试验地点
- 32
- 主要终点
- Percentage of Participants With Objective Response (OR) Per the Lugano Classification According to Independent Radiology Review Committee (IRRC) in Cohort 1
研究概览
简要总结
The goal of this clinical study is to test how well the study drug, brexucabtagene autoleucel (KTE-X19), works in participants with relapsed/refractory (r/r) mantle cell lymphoma (MCL).
详细描述
Study KTE-C19-102 enrolled participants with r/r MCL who have been treated with up to 5 prior regimens including a Bruton's tyrosine kinase inhibitor (BTKi) in Cohort 1 and Cohort 2. However, to fulfill FDA Postmarketing Requirement, Cohort 3 is added to the study. It will include participants with r/r MCL who have been treated with up to 5 prior regimens but have not received prior therapy with a BTKi.
The primary analysis in Cohort 1 and Cohort 2 is already completed. Data for Cohort 3 will be analyzed separately. Therefore, details for Cohort 3 were registered separately (NCT04880434) on ClinicalTrials.gov as this cohort will not be part of the main study analysis.
After the end of KTE-C19-102, subjects who received an infusion of anti-CD19 CAR T cells will complete the remainder of the 15-year follow-up assessments in a separate long-term follow-up study, KT-US-982-5968
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
- •Up to 5 prior regimens for Mantle cell lymphoma. Prior therapy must have included:
- •Anthracycline or bendamustine-containing chemotherapy and
- •Anti-CD20 monoclonal antibody therapy and
- •Ibrutinib or acalabrutinib
- •At least 1 measurable lesion
- •Platelet count ≥ 75,000/uL
- •Creatinine clearance (as estimated by Cockcroft Gault) > or = to 60 mL/min
- •Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings
- •Baseline oxygen saturation >92% on room air.
排除标准
- •Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV positive). A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per standard serological and genetic testing
- •History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome, or any autoimmune disease with central nervous system (CNS) involvement
- •Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Axicabtagene ciloleucel/brexucabtagene autoleucel (KTE-X19)
Participants with relapsed/refractory mantle cell lymphoma (MCL) will receive conditioning chemotherapy (CTE) consisting of fludarabine 30 mg/m^2/day and cyclophosphamide 500 mg/m^2/day intravenous (IV) infusion for 3 days followed by a single infusion of axicabtagene ciloleucel at a targeted dose of 2 x 10^6 anti-CD19 chimeric antigen receptor (CAR) T cells/kg on Day 0 or brexucabtagene autoleucel (KTE-X19) at a targeted dose of 2 x 10^6 CAR T cells/kg, with a maximum dose of 2 x 10^8 anti-CD19 CAR T cells for participants ≥ 100 kg on Day 0 in Cohort 1 or brexucabtagene autoleucel at a targeted dose of 0.5 x 10^6 anti-CD19 CAR T cells/kg, with a maximum dose of 0.5 x 10^8 anti-CD19 CAR T cells for participants ≥ 100 kg on Day 0 in Cohort 2.
干预措施: brexucabtagene autoleucel (Biological)
Axicabtagene ciloleucel/brexucabtagene autoleucel (KTE-X19)
Participants with relapsed/refractory mantle cell lymphoma (MCL) will receive conditioning chemotherapy (CTE) consisting of fludarabine 30 mg/m^2/day and cyclophosphamide 500 mg/m^2/day intravenous (IV) infusion for 3 days followed by a single infusion of axicabtagene ciloleucel at a targeted dose of 2 x 10^6 anti-CD19 chimeric antigen receptor (CAR) T cells/kg on Day 0 or brexucabtagene autoleucel (KTE-X19) at a targeted dose of 2 x 10^6 CAR T cells/kg, with a maximum dose of 2 x 10^8 anti-CD19 CAR T cells for participants ≥ 100 kg on Day 0 in Cohort 1 or brexucabtagene autoleucel at a targeted dose of 0.5 x 10^6 anti-CD19 CAR T cells/kg, with a maximum dose of 0.5 x 10^8 anti-CD19 CAR T cells for participants ≥ 100 kg on Day 0 in Cohort 2.
干预措施: Cyclophosphamide (Drug)
Axicabtagene ciloleucel/brexucabtagene autoleucel (KTE-X19)
Participants with relapsed/refractory mantle cell lymphoma (MCL) will receive conditioning chemotherapy (CTE) consisting of fludarabine 30 mg/m^2/day and cyclophosphamide 500 mg/m^2/day intravenous (IV) infusion for 3 days followed by a single infusion of axicabtagene ciloleucel at a targeted dose of 2 x 10^6 anti-CD19 chimeric antigen receptor (CAR) T cells/kg on Day 0 or brexucabtagene autoleucel (KTE-X19) at a targeted dose of 2 x 10^6 CAR T cells/kg, with a maximum dose of 2 x 10^8 anti-CD19 CAR T cells for participants ≥ 100 kg on Day 0 in Cohort 1 or brexucabtagene autoleucel at a targeted dose of 0.5 x 10^6 anti-CD19 CAR T cells/kg, with a maximum dose of 0.5 x 10^8 anti-CD19 CAR T cells for participants ≥ 100 kg on Day 0 in Cohort 2.
干预措施: Fludarabine (Drug)
Axicabtagene ciloleucel/brexucabtagene autoleucel (KTE-X19)
Participants with relapsed/refractory mantle cell lymphoma (MCL) will receive conditioning chemotherapy (CTE) consisting of fludarabine 30 mg/m^2/day and cyclophosphamide 500 mg/m^2/day intravenous (IV) infusion for 3 days followed by a single infusion of axicabtagene ciloleucel at a targeted dose of 2 x 10^6 anti-CD19 chimeric antigen receptor (CAR) T cells/kg on Day 0 or brexucabtagene autoleucel (KTE-X19) at a targeted dose of 2 x 10^6 CAR T cells/kg, with a maximum dose of 2 x 10^8 anti-CD19 CAR T cells for participants ≥ 100 kg on Day 0 in Cohort 1 or brexucabtagene autoleucel at a targeted dose of 0.5 x 10^6 anti-CD19 CAR T cells/kg, with a maximum dose of 0.5 x 10^8 anti-CD19 CAR T cells for participants ≥ 100 kg on Day 0 in Cohort 2.
干预措施: Axicabtagene Ciloleucel (Drug)
结局指标
主要结局
Percentage of Participants With Objective Response (OR) Per the Lugano Classification According to Independent Radiology Review Committee (IRRC) in Cohort 1
时间窗: Up to 7.8 years
OR: complete metabolic response(CMR),complete radiological response(CRR),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 (EOT).PRR: ≥ 50% decrease in sum of the product of the diameters(SPD)of up to 6 target measurable nodes and extra-nodal sites;absent/normal, regressed, but no increase of NMLs;spleen regressed by \> 50% in length beyond normal.
Percentage of Participants With Objective Response (OR) Per the Lugano Classification According to Independent Radiology Review Committee (IRRC) in Cohort 2
时间窗: Up to 7.8 years
OR: CMR, CRR, PMR, 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 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 EOT. PRR: ≥ 50% decrease in SPD of up to 6 target measurable 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
- Percentage of Participants With Objective Response (OR) as Per Investigator Assessment Determined by International Working Group (IWG) 2007 Criteria in Cohort 1(Up to 7.8 years)
- Progression Free Survival (PFS) in Cohort 1 as Per Investigator Response.(Up to 7.8 years)
- Progression Free Survival (PFS) in Cohort 2 as Per Investigator Response.(Up to 7.8 years)
- Percentage of Participants With Decrease in Post-brexucabtagene Autoleucel Infusion Hematology Toxicity Values by Worst Toxicity Grade(Up to 5 years)
- Percentage of Participants With Increase in Post-brexucabtagene Autoleucel Infusion Hematology Toxicity Values by Worst Toxicity Grade(Up to 5 years)
- Percentage of Participants With Decrease in Post-brexucabtagene Autoleucel Infusion Chemistry Toxicity Values by Worst Toxicity Grade(Up to 5 years)
- Percentage of Participants With Increase in Post-brexucabtagene Autoleucel Infusion Chemistry Toxicity Values by Worst Toxicity Grade(Up to 5 years)
- Peak Serum Levels of C-X-C Motif Chemokine 10 (CXCL10), Granzyme B, Interferon-Gamma (IFN-γ), Interleukin-1 Receptor Antagonist (IL-1RA), Interleukin (IL)-2, IL-6, IL-7, IL-8,IL-10, IL-15, and Tumor Necrosis Factor-Alpha (TNF-α) in Blood(Baseline up to Week 4)
- Percentage of Participants With Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Mobility Scale Score(Baseline, Week 4, Month 3, and Month 6)
- Duration of Response (DOR) in Cohort 1 as Per Investigator Response(Up to 7.8 years)
- Duration of Response (DOR) in Cohort 2 as Per Investigator Response(Up to 7.8 years)
- Percentage of Participants With Best Objective Response (BOR) as Per Investigator Assessment Determined by International Working Group (IWG) 2007 Criteria in Cohort 1(Up to 7.8 years)
- Percentage of Participants With Best Objective Response (BOR) as Per Investigator Assessment Determined by Lugano Classification in Cohort 2(Up to 7.8 years)
- Percentage of Participants With Objective Response (OR) as Per Investigator Assessment Determined by Lugano Classification in Cohort 2(Up to 7.8 years)
- Overall Survival in Cohort 1(Up to 7.8 years)
- Overall Survival in Cohort 2(Up to 7.8 years)
- Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAE)(Up to 5 years)
- Percentage of Participants With Anti-CD19 CAR Antibodies(Baseline up to Month 3)
- Maximum Number of CAR T Cells Measured Post-infusion(Up to Month 24)
- Peak Serum Levels of C-Reactive Protein (CRP) in Blood(Baseline up to Week 4)
- Peak Serum Levels of Ferritin, Interleukin-2 Receptor Alpha (IL-2Rα), Intercellular Adhesion Molecule-1 (ICAM-1), Perforin, Vascular Cell Adhesion Molecule-1 (VCAM-1) in Blood(Baseline up to Week 4)
- Percentage of Participants With Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Self-Care Scale Score(Baseline, Week 4, Month 3, and Month 6)
- Percentage of Participants With Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Usual Activity Scale Score(Baseline, Week 4, Month 3, and Month 6)
- Percentage of Participants With Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Pain / Discomfort Activity Scale Score(Baseline, Week 4, Month 3, and Month 6)
- Percentage of Participants With Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Anxiety / Depression Activity Scale Score(Baseline, Week 4, Month 3, and Month 6)
- Change Over Time in EQ-5D Visual Analogue Scale (VAS) Score(Baseline, Week 4, Month 3, and Month 6)