A Study Evaluating the Safety and Efficacy of GLPG5101 (19CP02) in Participants With Non-Hodgkin Lymphoma
- Conditions
- Relapsed/Refractory B-cell Non-Hodgkin LymphomaLymphomas Non-Hodgkin's B-Cell
- Interventions
- Genetic: GLPG5101
- Registration Number
- NCT06561425
- Lead Sponsor
- Galapagos NV
- Brief Summary
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.
- Detailed Description
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+
Participants per disease cohort will be treated at the selected RP2Ds for that disease subtype.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 250
- 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)
- 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)
- 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.
Key
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1 (Dose escalation phase): Dose level 1 GLPG5101 Participants will receive a single dose of GLPG5101 intravenous (IV) cell suspension for infusion at dose level 1 on Day 0. Phase 2 (Dose expansion phase): Indolent B-cell NHL GLPG5101 Participants with indolent B-cell NHL (FL and MZ) will receive a single dose of GLPG5101 IV cell suspension for infusion at RP2D level on Day 0. Phase 2 (Dose expansion phase): BL GLPG5101 Participants with BL will receive a single dose of GLPG5101 IV cell suspension for infusion at RP2D level on Day 0. Phase 2 (Dose expansion phase): PCNSL GLPG5101 Participants with PCNSL will receive a single dose of GLPG5101 IV cell suspension for infusion at RP2D level on Day 0. Phase 1 (Dose escalation phase): Dose level 3 GLPG5101 Participants will receive a single dose of GLPG5101 IV cell suspension for infusion at dose level 3 on Day 0. Phase 1 (Dose escalation phase): Dose level 2 GLPG5101 Participants will receive a single dose of GLPG5101 IV cell suspension for infusion at dose level 2 on Day 0. Phase 2 (Dose expansion phase): DLBCL GLPG5101 Participants with DLBCL will receive a single dose of GLPG5101 IV cell suspension for infusion at RP2D level on Day 0. Phase 2 (Dose expansion phase): High-risk DLBCL GLPG5101 Participants with High-risk DLBCL will receive a single dose of GLPG5101 IV cell suspension for infusion at RP2D level on Day 0. Phase 2 (Dose expansion phase): MCL GLPG5101 Participants with MCL will receive a single dose of GLPG5101 IV cell suspension for infusion at RP2D level on Day 0.
- Primary Outcome Measures
Name Time Method Phase 1: Number of participants with adverse events (AEs) and serious adverse events (SAEs) 2 years Phase 1: Number of participants with Dose-Limiting Toxicities (DLTs) 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 2 years For all cohorts except cohort 6b
Phase 2: Progression-free survival (PFS) 2 years For cohort 6b only
- Secondary Outcome Measures
Name Time Method Number of participants without minimal Residual Disease (MRD) at CR (DLBCL, MCL and DLBCL-RT) 2 years Pharmacokinetics (PK): Levels of anti-CD19 CAR T cells in blood at peak and over time 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: 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 For phase 1 and cohort 6b only
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 2 years Duration of response (DOR) 2 years Duration of complete response (DOCR) 2 years Event-free survival (EFS) 2 years Progression-free survival (PFS) 2 years Overall survival (OS) 2 years Phase 2: Change from baseline in measurement of health-related Quality of Life (HRQoL) using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and its CLL-specific module QLQ-CLL-17 (DLBCL-RT only), and EuroQol EQ-5D-5L 2 years
Trial Locations
- Locations (9)
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
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