A Phase 2 Multicenter Study Evaluating the Safety and the Efficacy of KTE-X19 in Adult Japanese Subjects With Relapsed/Refractory Mantle Cell Lymphoma or Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 25
- 试验地点
- 18
- 主要终点
- MCL Cohort: Objective Response Rate (ORR) Per Investigator Assessment
研究概览
简要总结
The goal of this clinical study is to learn more about KTE-X19, and how safe and effective it is in adult Japanese participants with relapsed/refractory (r/r) Mantle Cell Lymphoma (MCL) or r/r B-precursor Acute Lymphoblastic Leukemia (B-ALL).
The primary objectives of this study are to evaluate the efficacy of KTE-X19, as measured by:
- Objective response rate (ORR) per investigator assessment, in adult Japanese participants with r/r MCL
- Overall complete remission (OCR) defined as complete remission (CR) and complete remission with incomplete hematologic recovery (CRi) per investigator assessment, in adult Japanese participants with r/r ALL
详细描述
After completing at least 24 months in the study, all participants who received an infusion of KTE-X19 will be transitioned to a separate long-term follow-up (LTFU) study (KT-US-982-5968) to 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
- •MCL Cohort:
- •Pathologically confirmed MCL, with documentation of either overexpression of cyclin D1 or presence of t(11;14)
- •Up to 5 prior regimens for MCL. Prior therapy must have included:
- •Anthracycline-, bendamustine-, or high-dose cytarabine- containing chemotherapy, and
- •Anti-CD20 monoclonal antibody therapy, and
- •Bruton's tyrosine kinase inhibitor (BTKi)
- •Relapsed or refractory disease, defined by the following:
- •Disease progression after last regimen, or
- •Refractory disease is defined failure to achieve partial response (PR) or complete remission (CR) to the last regimen
- •At least 1 measurable lesion. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy
- •If the only measurable disease is lymph node disease, at least 1 lymph node should be ≥ 2 cm
- •ALL Cohort:
- •Relapsed or refractory B-ALL defined as one of the following:
- •Relapsed or refractory disease after one line of systemic therapy;
- •Primary refractory, or
- •First relapse if first remission ≤ 12 months
- •Relapsed or refractory disease after two or more lines of systemic therapy
- •Relapsed or refractory disease after allogeneic transplant provided individuals is at least 100 days from SCT at the time of enrollment and off of immunosuppressive medications for at least 4 weeks prior to enrollment
- •Morphological disease in the bone marrow (> 5% blasts)
- •Individuals with Philadelphia-positive (Ph+) disease are eligible if they are intolerant to tyrosine kinase inhibitor (TKI) therapy, or if they have relapsed/refractory disease despite treatment with at least 2 different TKIs
排除标准
- •MCL Cohort:
- •History of malignancy other than nonmelanomatous skin cancer or carcinoma in situ (eg, cervix, bladder, breast) unless disease-free for at least 3 years
- •Autologous SCT (autoSCT) within 6 weeks of planned KTE-X19 infusion
- •History of alloSCT with the exception of individuals with no donor cells detected on chimerism > 100 days after alloSCT
- •Prior CD19 targeted therapy
- •Prior CAR therapy or other genetically modified T-cell therapy
- •History of hypersensitivity to any of the ingredients of KTE-X19 or to any of the animal-derived ingredients (bovine and rodent) used in the manufacturing process of KTE-X19
- •ALL Cohort:
- •Diagnosis of Burkitt's leukemia/lymphoma according to World Health Organization (WHO) classification or chronic myelogenous leukemia lymphoid blast crisis
- •History of malignancy other than non-melanoma skin cancer or carcinoma in situ (eg, cervix, bladder, breast) unless disease free for at least 3 years
- •History of hypersensitivity to any of the ingredients of KTE-X19 or to any of the animal-derived ingredients (bovine and rodent) used in the manufacturing process of KTE-X19
- •Note: Other protocols defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
MCL Cohort- KTE-X19
Participants will receive cyclophosphamide 500 mg/m^2/day intravenously (IV) and fludarabine 30 mg/m^2/day IV lymphodepletion chemotherapy for 3 days followed by KTE-X19 administered intravenously at a target dose of 2 x 10^6 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) T cells/kg on Day 0.
For participants weighing ≥ 100 kg, a maximum flat dose of 2 x 10^8 anti-CD19 CAR T cells will be administered.
干预措施: Fludarabine (Drug)
MCL Cohort- KTE-X19
Participants will receive cyclophosphamide 500 mg/m^2/day intravenously (IV) and fludarabine 30 mg/m^2/day IV lymphodepletion chemotherapy for 3 days followed by KTE-X19 administered intravenously at a target dose of 2 x 10^6 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) T cells/kg on Day 0.
For participants weighing ≥ 100 kg, a maximum flat dose of 2 x 10^8 anti-CD19 CAR T cells will be administered.
干预措施: KTE-X19 (Drug)
MCL Cohort- KTE-X19
Participants will receive cyclophosphamide 500 mg/m^2/day intravenously (IV) and fludarabine 30 mg/m^2/day IV lymphodepletion chemotherapy for 3 days followed by KTE-X19 administered intravenously at a target dose of 2 x 10^6 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) T cells/kg on Day 0.
For participants weighing ≥ 100 kg, a maximum flat dose of 2 x 10^8 anti-CD19 CAR T cells will be administered.
干预措施: Cyclophosphamide (Drug)
ALL Cohort- KTE-X19
Participants will receive cyclophosphamide 900 mg/m^2/day intravenously (IV) for 1 day and fludarabine 25 mg/m^2/day IV lymphodepletion chemotherapy for 3 days followed by KTE-X19 administered intravenously at a target dose of 1 x 10^6 19 CAR T cells/kg on Day 0.
For participants weighing ≥ 100 kg, a maximum flat dose of 1 x 10^8 anti-CD19 CAR T cells will be administered.
干预措施: KTE-X19 (Drug)
ALL Cohort- KTE-X19
Participants will receive cyclophosphamide 900 mg/m^2/day intravenously (IV) for 1 day and fludarabine 25 mg/m^2/day IV lymphodepletion chemotherapy for 3 days followed by KTE-X19 administered intravenously at a target dose of 1 x 10^6 19 CAR T cells/kg on Day 0.
For participants weighing ≥ 100 kg, a maximum flat dose of 1 x 10^8 anti-CD19 CAR T cells will be administered.
干预措施: Cyclophosphamide (Drug)
ALL Cohort- KTE-X19
Participants will receive cyclophosphamide 900 mg/m^2/day intravenously (IV) for 1 day and fludarabine 25 mg/m^2/day IV lymphodepletion chemotherapy for 3 days followed by KTE-X19 administered intravenously at a target dose of 1 x 10^6 19 CAR T cells/kg on Day 0.
For participants weighing ≥ 100 kg, a maximum flat dose of 1 x 10^8 anti-CD19 CAR T cells will be administered.
干预措施: Fludarabine (Drug)
结局指标
主要结局
MCL Cohort: Objective Response Rate (ORR) Per Investigator Assessment
时间窗: Up to 24 months
ORR is defined as the incidence of a complete remission (CR) or a partial remission (PR) per the Lugano Classification.
ALL Cohort: Overall Complete Remission (OCR) Rate
时间窗: Up to 24 months
OCR rate is defined as the percentage of participants achieving CR/complete remission with incomplete hematologic recovery (CRi) per investigator assessment.
次要结局
- ALL Cohort: Allogeneic Stem Cell Transplant (alloSCT) rate(Up to 24 months)
- MCL and ALL Cohort: Levels of Anti-Cluster of Differentiation 19 (Anti-CD19) CAR T Cells in Blood(Up to 24 months)
- MCL Cohort: Levels of Cytokines in Serum(Up to Day 28)
- MCL Cohort: Duration of Response (DOR)(Up to 24 months)
- MCL Cohort: Best Objective Response (BOR)(Up to 24 months)
- MCL Cohort: Progression-Free Survival (PFS)(Up to 24 months)
- ALL Cohort: Minimal Residual Disease (MRD) Negativity Rate(Up to 24 months)
- ALL Cohort: Relapse-Free Survival (RFS)(Up to 24 months)
- MCL and ALL Cohorts: Overall Survival (OS)(Up to 24 months)
- ALL Cohorts: DOR(Up to 24 months)
- MCL and ALL Cohorts: Percentages of Participants Experiencing Treatment-emergent Adverse Event (TEAEs), Serious Adverse Event (SAEs) and Deaths(First infusion date up to 24 months)
- MCL and ALL Cohorts: Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values(First infusion date up to 24 months)