A Phase 1/2 Open-label, Multicenter Study Evaluating the Safety and Efficacy of KITE-363 or KITE-753, Autologous Anti-CD19/CD20 CAR T-cell Therapies, in Subjects With Relapsed and/or Refractory B-cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 247
- 试验地点
- 33
- 主要终点
- Phase 1a: Percentage of Participants Experiencing Adverse Events Defined as Dose-limiting Toxicities (DLTs) After the Infusion of KITE-363 or KITE-753
研究概览
简要总结
The goal of this clinical study is to learn more about the safety and effectiveness of the study drugs, KITE-363 and KITE-753, in participants with relapsed and/or refractory B-cell lymphoma.
详细描述
Eligible study participants who have received IP administration with either KITE-363 or KITE-753 will transition to a separate Long-term Follow-up study (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
- Na
- 干预模型
- Sequential
- 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
- •for Phase 1a/b and Phase 2
- •Relapsed and/or refractory B-cell lymphoma (R/R BCL).
- •At least 1 measurable lesion.
- •Adequate organ and bone marrow (BM) function.
排除标准
- •for Phase 1a/b and Phase 2
- •- History of chimeric antigen receptor (CAR) therapy or other genetically modified T cell therapy.
- •History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg, cervix, bladder, or breast) unless disease free and without anticancer therapy (with the exception of hormonal therapy in the case of breast cancer) for at least 3 years.
- •History of allogeneic stem cell transplant (allo-SCT).
- •Auto-SCT within 6 weeks before the planned KITE-363 or KITE-753 infusion.
- •Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requires intravenous (IV) antimicrobials for management.
- •Known history of human immunodeficiency virus (HIV) infection, hepatitis B virus (HBV) (hepatitis B surface [HBs] antigen [HBsAg] positive) infection, or hepatitis C (anti-hepatitis C virus [HCV] positive) infection. History of a hepatitis B or C infection is permitted if the viral load is undetectable per quantitative polymerase chain reaction (qPCR) or nucleic acid testing.
- •Individuals with suspicion and/or evidence of primary or secondary CNS lymphoma.
- •History or presence of a CNS disorder.
- •History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, active arrhythmia, New York Heart Association Class II or greater congestive heart failure or other clinically significant cardiac disease within the 6 months before enrollment.
- •Primary immunodeficiency.
- •History of autoimmune disease resulting in or requiring systemic immunosuppression and/or systemic disease-modifying agents within the last 90 days.
- •Individuals with full thickness lymphoma involvement of the gastric or intestinal lining and/or transmural gastrointestinal (GI) tract involvement, or with concern for gastric or intestinal perforation or known contained gastric or intestinal perforation.
- •Females of childbearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. Females who have undergone surgical sterilization or have been postmenopausal for at least 2 years are not considered to be of childbearing potential.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Phase 1 a/b: KITE-363
Phase 1a (Dose escalation): Participants with r/r large B-cell lymphoma will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single target starting dose of KITE-363 chimeric antigen receptor (CAR) transduced autologous T cells. Based on dose limiting toxicities (DLTs) observed in the first cohort, additional participants will be enrolled and administered escalating dose of KITE-363.
Phase 1b (Dose expansion): After completion of dose escalation, additional participants with r/r B-cell lymphoma across different disease indications will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single dose of KITE-363 at 1 or more dose-level deemed to be tolerable.
[Recruitment completed for this arm]
干预措施: KITE-363 (Biological)
Phase 1 a/b: KITE-753
Phase 1a (Dose escalation): Participants with r/r large B-cell lymphoma will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single target starting dose of KITE-753 chimeric antigen receptor (CAR) transduced autologous T cells. Based on dose limiting toxicities (DLTs) observed in the first cohort, additional participants will be enrolled and administered escalating dose of KITE-753.
Phase 1b (Dose expansion): After completion of dose escalation, additional participants with r/r B-cell lymphoma across different disease indications will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single dose of KITE-753 at 1 or more dose-level deemed to be tolerable.
[Recruitment open for frontline LBCL and r/r MCL for this arm]
干预措施: Cyclophosphamide (Drug)
Phase 1 a/b: KITE-753
Phase 1a (Dose escalation): Participants with r/r large B-cell lymphoma will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single target starting dose of KITE-753 chimeric antigen receptor (CAR) transduced autologous T cells. Based on dose limiting toxicities (DLTs) observed in the first cohort, additional participants will be enrolled and administered escalating dose of KITE-753.
Phase 1b (Dose expansion): After completion of dose escalation, additional participants with r/r B-cell lymphoma across different disease indications will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single dose of KITE-753 at 1 or more dose-level deemed to be tolerable.
[Recruitment open for frontline LBCL and r/r MCL for this arm]
干预措施: Fludarabine (Drug)
Phase 1 a/b: KITE-753
Phase 1a (Dose escalation): Participants with r/r large B-cell lymphoma will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single target starting dose of KITE-753 chimeric antigen receptor (CAR) transduced autologous T cells. Based on dose limiting toxicities (DLTs) observed in the first cohort, additional participants will be enrolled and administered escalating dose of KITE-753.
Phase 1b (Dose expansion): After completion of dose escalation, additional participants with r/r B-cell lymphoma across different disease indications will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single dose of KITE-753 at 1 or more dose-level deemed to be tolerable.
[Recruitment open for frontline LBCL and r/r MCL for this arm]
干预措施: KITE-753 (Biological)
Phase 2: KITE-753
Participants with r/r large B-cell lymphoma who have received at least 2 prior lines of systemic therapy will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single target starting dose of KITE-753 chimeric antigen receptor (CAR) transduced autologous T cells /kg intravenously (IV).
干预措施: Fludarabine (Drug)
Phase 2: KITE-753
Participants with r/r large B-cell lymphoma who have received at least 2 prior lines of systemic therapy will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single target starting dose of KITE-753 chimeric antigen receptor (CAR) transduced autologous T cells /kg intravenously (IV).
干预措施: KITE-753 (Biological)
Phase 2: KITE-753
Participants with r/r large B-cell lymphoma who have received at least 2 prior lines of systemic therapy will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single target starting dose of KITE-753 chimeric antigen receptor (CAR) transduced autologous T cells /kg intravenously (IV).
干预措施: Cyclophosphamide (Drug)
Phase 1 a/b: KITE-363
Phase 1a (Dose escalation): Participants with r/r large B-cell lymphoma will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single target starting dose of KITE-363 chimeric antigen receptor (CAR) transduced autologous T cells. Based on dose limiting toxicities (DLTs) observed in the first cohort, additional participants will be enrolled and administered escalating dose of KITE-363.
Phase 1b (Dose expansion): After completion of dose escalation, additional participants with r/r B-cell lymphoma across different disease indications will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single dose of KITE-363 at 1 or more dose-level deemed to be tolerable.
[Recruitment completed for this arm]
干预措施: Cyclophosphamide (Drug)
Phase 1 a/b: KITE-363
Phase 1a (Dose escalation): Participants with r/r large B-cell lymphoma will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single target starting dose of KITE-363 chimeric antigen receptor (CAR) transduced autologous T cells. Based on dose limiting toxicities (DLTs) observed in the first cohort, additional participants will be enrolled and administered escalating dose of KITE-363.
Phase 1b (Dose expansion): After completion of dose escalation, additional participants with r/r B-cell lymphoma across different disease indications will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single dose of KITE-363 at 1 or more dose-level deemed to be tolerable.
[Recruitment completed for this arm]
干预措施: Fludarabine (Drug)
结局指标
主要结局
Phase 1a: Percentage of Participants Experiencing Adverse Events Defined as Dose-limiting Toxicities (DLTs) After the Infusion of KITE-363 or KITE-753
时间窗: Up to 28 days
DLTs are defined as the KITE-363-related or KITE-753-related events with onset within the first 28 days after the infusion of KITE-363 or KITE-753 respectively.
Phase 1b: Objective Response Rate (ORR) for KITE-363 and KITE-753 as per investigator's assessment.
时间窗: Up to 15 years
ORR is defined as the percentage of participants with a complete response (CR) or a partial response (PR) by the International Working Group (IWG) Lugano Response Criteria for Malignant Lymphoma (Cheson 2014) as determined by investigator assessment.
Phase 1a: Percentage of Participants Experiencing Adverse Events Defined as Dose-limiting Toxicities (DLTs) After the Infusion of KITE-363 or KITE-753
时间窗: Up to 28 days
DLTs are defined as the KITE-363-related or KITE-753-related events with onset within the first 28 days after the infusion of KITE-363 or KITE-753 respectively.
Phase 2: ORR as per central assessment for KITE-753
时间窗: Up to 15 years
次要结局
- Phase 1a/b: Percentage of Participants Experiencing Adverse Events (AEs) After the Infusion of KITE-363 and KITE-753(Up to 15 years)
- Phase 1a/b: Percentage of Participants Experiencing Serious AEs (SAEs) After the Infusion of KITE-363 and KITE-753(Up to 15 years)
- Phase 1a/b: Peak Serum Levels of Key Analytes Correlates of Acute Phase Response: Ferritin(Up to 3 months)
- Phase 1a/b: Time To Next Treatment (TTNT) for KITE-363 and KITE-753(Up to 15 years)
- Phase 1a/b: Complete Response (CR) Rate for KITE-363 and KITE-753(Up to 15 years)
- Phase 1a/b: Duration of Response (DOR) for KITE-363 and KITE-753(Up to 15 years)
- Phase 1a/b: Progression-Free Survival (PFS) for KITE-363 and KITE-753(Up to 15 years)
- Phase 1a/b: Overall Survival (OS) for KITE-363 and KITE-753(Up to 15 years)
- Phase 1a/b: Percentage of Participants who Develop Antibodies to KITE-363 and KITE-753 Chimeric Antigen Receptor (CAR) T Cells(Enrollment; up to 12 months)
- Phase 1a/b: Levels of KITE-363 and KITE-753 CAR T Cells(Up to 15 years)
- Phase 1a/b: Peak Serum Levels of Key Analytes Homeostatic/Proliferative Cytokines: Interleukin (IL)-2, IL-7, and IL-15(Up to 3 months)
- Phase 1a/b: Peak Serum Levels of Key Analytes Inflammatory/Immune Modulating Cytokines: IFN-γ, IL-6, IL-10, IL-17, IL-1RA, Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF), and Tumor Necrosis Factor-Alpha (TNF-α)(Up to 3 months)
- Phase 1a/b: Peak Serum Levels of Key Analytes Correlates of Acute Phase Response: C-Reactive Protein (CRP)(Up to 3 months)
- Phase 1a/b: Peak Serum Levels of Key Analytes Correlates of Acute Phase Response: Soluble IL-2 Receptor Alpha (Sil-2Rα)(Up to 3 months)
- Phase 1a/b: Peak Serum Levels of Key Analytes Chemokines: IL-8, C-X-C Motif Chemokine Ligand-10 (CXCL-10), and Monocyte Chemotactic Protein-1 (MCP-1)(Up to 3 months)
- Phase 1a/b: Peak Serum Levels of Key Analytes Immune-Effector Molecules: Perforin, Granzyme A, and Granzyme B(Up to 3 months)
- Phase 2: CR rate for KITE-753(Up to 15 years)
- Phase 2: DOR for KITE-753(Up to 15 years)
- Phase 2: PFS for KITE-753(Up to 15 years)
- Phase 2: OS for KITE-753(Up to 15 years)
- Phase 2: Percentage of Participants Experiencing Adverse Events (AEs) After the Infusion of KITE-753(Up to 15 years)
- Phase 2: Percentage of Participants Experiencing Serious AEs (SAEs) After the Infusion of KITE-753(Up to 15 years)
- Phase 2: ctDNA MRD-Negative CR Rate of KITE-753(Up to 15 years)
- Phase 2: Overall ctDNA MRD Negativity of KITE-753(Up to 15 years)