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.
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: After determination of the RP2Ds, the study continues with the dose expansion phase. Different doses deemed safe by the SRC within the same indication may be explored in the dose-expansion phase to help select the optimal dose for further development. During this phase, participants will be enrolled into separate disease cohorts as defined by their NHL subtype: * Cohort 1a: DLBCL second line or greater (2L+) * Cohort 1b: DLBCL 2L+ with secondary central nervous system lymphoma (SCNSL) * Cohort 2: High-risk first-line DLBCL * Cohort 3: Indolent B-cell NHL (FL and MZL third-line or greater \[3L+\]) * Cohort 4: MCL 2L+ * Cohort 5: BL 2L+ * Cohort 6a: PCNSL 2L+ * Cohort 6b: PCNSL first-line consolidation * Cohort 7: DLBCL-RT 2L+ * Cohort 8: CLL/SLL (r/r) Participants per disease cohort will be treated at the selected RP2Ds for that disease subtype.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
Autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy
Tufts Medical Center
Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Phase 1: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Time frame: 2 years
Phase 1: Number of participants with Dose-Limiting Toxicities (DLTs)
Time frame: 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)
For all cohorts
Time frame: 2 years
Phase 2: Number of participants with AEs and SAEs
Time frame: 2 years
Number of participants with AEs of special interests
Time frame: 2 years
Number of participants with OR per the Lugano Classification or IPCG criteria
For phase 1 and cohort 6b only
Time frame: 2 years
Number of participants with OR per International workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria (DLBCL-RT [cohort 7] only
Time frame: 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)
Time frame: 2 years
Duration of response (DOR)
Time frame: 2 years
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NONE
Enrollment
274
Antwerp University Hospital
Edegem, Belgium
UZ Leuven
Leuven, Belgium
CHU De Liège
Liège, Belgium
Cliniques Universitaires Saint-Luc
Woluwe-Saint-Lambert, Belgium
Academisch Medisch Centrum
Amsterdam, Netherlands
Leiden University Medical Center
Leiden, Netherlands
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Rotterdam, Netherlands
Duration of complete response (DOCR)
Time frame: 2 years
Progression-free survival (PFS)
Time frame: 2 years
Overall survival (OS)
Time frame: 2 years
Number of participants without minimal Residual Disease (MRD) at CR (DLBCL, MCL, DLBCL-RT, and CLL/SLL)
Time frame: 2 years
Pharmacokinetics (PK): Levels of anti-CD19 CAR T cells in blood at peak and over time
Time frame: 2 years
Pharmacodynamics (PD): Levels of chemokines in serum over time
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 2 years