A Phase I/II, Multicenter Study Evaluating the Feasibility, Safety, and Efficacy of Point-of-care Manufactured GLPG5101 (19CP02) in Subjects With Relapsed/Refractory B-cell Non-Hodgkin Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 130
- 试验地点
- 18
- 主要终点
- Phase 1: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
研究概览
简要总结
This study is evaluating whether an experimental treatment called GLPG5101 helps to treat non-Hodgkin lymphoma (NHL) and if it is safe to use.
This study will be carried out in 2 phases:
- The first phase is to see which doses of GLPG5101 work best with the least number of side effects.
- In the second phase, participants will receive the selected dose(s) based on the results in the first phase.
详细描述
Phase 1 Dose escalation phase:
The dose escalation phase is designed to select the doses for dose expansion based on efficacy and safety outcomes.
Three dose levels of GLPG5101 will be evaluated to determine the recommended phase 2 doses (RP2Ds).
Participants with aggressive or indolent forms of Relapsed/Refractory B-cell Non-Hodgkin Lymphoma (r/r NHL) including follicular lymphoma (FL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), and Diffuse large B-cell lymphoma (DLBCL) will be enrolled. In case any safety or efficacy differences based on histological subtype of the disease are observed, it may be decided to make decisions regarding dose escalation for a specific subtype(s) independently, upon recommendation by the Safety Review Committee (SRC). Hence the RP2Ds may be different for different subtypes.
Phase 2 Dose expansion phase:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Histologically confirmed diagnosis of one of the following NHL subtypes: DLBCL, FL grade 1, 2 or 3A, MZL, MCL, BL, PCNSL, DLBCL-RT, High Grade B-cell Lymphoma (HGBL), CLL/SLL
- •Relapsed or refractory disease
- •Presence of at least one measurable lesion according to the Lugano classification (except for PCNSL subjects ineligible for ASCT after induction therapy, Cohort 6b; and except for CLL/SLL subjects without a measurable lesion or a PET positive lesion will be eligible if they have splenomegaly (spleen size >13 cm) and bone marrow infiltration with lymphoma)
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (Participants with ECOG 2 must have serum albumin ≥ 3.4 gram/deciliter)
- •Adequate bone marrow function
- •Adequate renal, hepatic and pulmonary function
- •Women of childbearing potential must have a negative serum pregnancy test at screening and prior to the first dose of conditioning chemotherapy
- •Women of childbearing potential and all male subjects must agree to use highly effective methods of contraception and agree to remain on a highly effective method of contraception from the time of signing the informed consent form until at least 12 months after GLPG5101 infusion. Subjects must agree to not donate eggs or sperm during this period.
排除标准
- •Selected prior treatments as defined in the protocol
- •History of another primary malignancy that requires intervention beyond surveillance or that has not been in remission for at least 3 years. (exceptions per protocol)
- •Toxicity from previous anticancer therapy that has not resolved to baseline levels or to ≤ Grade 2
- •Active central nervous system (CNS) involvement (lesion on contrast-enhanced CT/MRI brain, malignant B cells in CSF) by disease under study (exceptions per protocol)
- •Clinically significant cardiac disease
- •Primary immunodeficiency
- •Stroke or seizure within 6 months of screening
- •History of autoimmune disease requiring systemic immunosuppression or disease modifying treatment within 28 days before screening
- •Infection with human immunodeficiency virus (HIV), active hepatitis B or active hepatitis C virus
- •Systemic fungal, bacterial, viral, or other infection that is not controlled
研究组 & 干预措施
Phase 2 (Dose expansion phase): Cohort 6b: PCNSL first-line consolidation
Participants in this cohort will receive a single dose of GLPG5101 IV cell suspension for infusion at the selected RP2D level for this disease subtype on Day 0
干预措施: GLPG5101 (Genetic)
Phase 1 (Dose escalation phase): Dose level 3
Participants will receive a single dose of GLPG5101 IV cell suspension for infusion at dose level 3 on Day 0.
干预措施: GLPG5101 (Genetic)
Phase 1 (Dose escalation phase): Dose level 1
Participants will receive a single dose of GLPG5101 intravenous (IV) cell suspension for infusion at dose level 1 on Day 0.
干预措施: GLPG5101 (Genetic)
Phase 2 (Dose expansion phase): Cohort 7: DLBCL-RT 2L+
Participants in this cohort will receive a single dose of GLPG5101 IV cell suspension for infusion at the selected RP2D level for this disease subtype on Day 0
干预措施: GLPG5101 (Genetic)
Phase 1 (Dose escalation phase): Dose level 2
Participants will receive a single dose of GLPG5101 IV cell suspension for infusion at dose level 2 on Day 0.
干预措施: GLPG5101 (Genetic)
Phase 2 (Dose expansion phase): Cohort 5: BL 2L+
Participants in this cohort will receive a single dose of GLPG5101 IV cell suspension for infusion at the selected RP2D level for this disease subtype on Day 0
干预措施: GLPG5101 (Genetic)
Experimental: Phase 2 (Dose expansion phase): Cohort 8 CLL/SLL (r/r)
Participants in this cohort will receive a single dose of GLPG5101 IV cell suspension for infusion at the selected RP2D level for this disease subtype on Day 0
干预措施: GLPG5101 (Genetic)
Phase 2 (Dose expansion phase): Cohort 6a: PCNSL 2L+
Participants in this cohort will receive a single dose of GLPG5101 IV cell suspension for infusion at the selected RP2D level for this disease subtype on Day 0
干预措施: GLPG5101 (Genetic)
Phase 2 (Dose expansion phase): Cohort 3: Indolent B-cell NHL (FL and MZL 3L+)
Participants in this cohort will receive a single dose of GLPG5101 IV cell suspension for infusion at the selected RP2D level for this disease subtype on Day 0
干预措施: GLPG5101 (Genetic)
Phase 2 (Dose expansion phase): Cohort 4: MCL 2L+
Participants in this cohort will receive a single dose of GLPG5101 IV cell suspension for infusion at the selected RP2D level for this disease subtype on Day 0
干预措施: GLPG5101 (Genetic)
Phase 2 (Dose expansion phase): Cohort 1b: DLBCL 2L+ SCNSL
Participants in this cohort will receive a single dose of GLPG5101 IV cell suspension for infusion at the selected RP2D level for this disease subtype on Day 0
干预措施: GLPG5101 (Genetic)
Phase 2 (Dose expansion phase): Cohort 1a: DLBCL 2L+
Participants in this cohort will receive a single dose of GLPG5101 IV cell suspension for infusion at the selected RP2D level for this disease subtype on Day 0
干预措施: GLPG5101 (Genetic)
Phase 2 (Dose expansion phase): Cohort 2: High-risk first-line DLBCL
Participants in this cohort will receive a single dose of GLPG5101 IV cell suspension for infusion at the selected RP2D level for this disease subtype on Day 0
干预措施: GLPG5101 (Genetic)
结局指标
主要结局
Phase 1: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
时间窗: 2 years
Phase 1: Number of participants with Dose-Limiting Toxicities (DLTs)
时间窗: From first dose up to Day 28
Phase 2: Number of participants with objective response (OR) per the Lugano Classification or International Primary central nervous system lymphoma Collaborative Group (IPCG) criteria for PCNSL or per iwCLL (CLL [Cohort 8] and DLBCL-RT [Cohort 7] only)
时间窗: 2 years
For all cohorts
Phase 1: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
时间窗: 2 years
Phase 1: Number of participants with Dose-Limiting Toxicities (DLTs)
时间窗: From first dose up to Day 28
次要结局
- Phase 2: Number of participants with AEs and SAEs(2 years)
- Number of participants with OR per International workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria (DLBCL-RT [cohort 7] only(2 years)
- Number of participants with complete response (CR) per Lugano Classification or IPCG criteria for PCNSL or per iwCLL (CLL [Cohort 8] and DLBCL-RT [Cohort 7] only)(2 years)
- Duration of response (DOR)(2 years)
- Duration of complete response (DOCR)(2 years)
- Overall survival (OS)(2 years)
- Pharmacokinetics (PK): Levels of anti-CD19 CAR T cells in blood at peak and over time(2 years)
- Number of participants with AEs of special interests(2 years)
- Number of participants with OR per the Lugano Classification or IPCG criteria(2 years)
- Progression-free survival (PFS)(2 years)
- Number of participants without minimal Residual Disease (MRD) at CR (DLBCL, MCL, DLBCL-RT, and CLL/SLL)(2 years)
- Pharmacodynamics (PD): Levels of chemokines in serum over time(Day 7 before infusion, Day 0, Day 1, Day 4, Day 7, Day 10, Day 14, Day 21, Day 28)
- PD: Levels of cytokines in serum over time(Day 7 before infusion, Day 0, Day 1, Day 4, Day 7, Day 10, Day 14, Day 21, Day 28)
- Percentage of successfully manufactured GLPG5101 products within the predefined release specifications(From leukapheresis to infusion)
- Phase 2: Change from baseline in measurement of HRQoL using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and its CLL-specific module QLQ-CLL-17 (DLBCL-RT and CLL only), and EuroQol EQ-5D-5L(2 years)
- PD: Levels of cytokines in serum over time(Day 7 before infusion, Day 0, Day 1, Day 4, Day 7, Day 10, Day 14, Day 21, Day 28)
- Percentage of successfully manufactured GLPG5101 products within the predefined release specifications(From leukapheresis to infusion)
- Overall survival (OS)(2 years)
- Pharmacodynamics (PD): Levels of chemokines in serum over time(Day 7 before infusion, Day 0, Day 1, Day 4, Day 7, Day 10, Day 14, Day 21, Day 28)
- Phase 2: Number of participants with AEs and SAEs(2 years)
- Number of participants with AEs of special interests(2 years)
- Number of participants with OR per the Lugano Classification or IPCG criteria(2 years)
- Number of participants with OR per International workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria (DLBCL-RT [cohort 7] only(2 years)
- Duration of response (DOR)(2 years)
- Duration of complete response (DOCR)(2 years)
- Progression-free survival (PFS)(2 years)
- Pharmacokinetics (PK): Levels of anti-CD19 CAR T cells in blood at peak and over time(2 years)