Clinical trial NCT06561425: A Study Evaluating the Safety and Efficacy of GLPG5101 (19CP02) in Participants With Non-Hodgkin Lymphoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Relapsed/Refractory B-cell Non-Hodgkin Lymphoma
Lymphomas Non-Hodgkin&#39;s B-Cell
Keywords: non-Hodgkin lymphoma (NHL)
Follicular lymphoma (FL)
Marginal zone lymphoma (MZL)
Mantle cell lymphoma (MCL)
Burkitt lymphoma (BL)
Primary central nervous system lymphoma (PCNSL)
Diffuse large B-cell lymphoma (DLBCL)
CAR T-cell therapy
Diffuse large B-cell lymphoma - Richter Transformation (DLBCL-RT)
Lead sponsor: Galapagos NV
Sponsor class: INDUSTRY
First posted: 2024-08-20
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: Key Inclusion Criteria:

* 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 Exclusion Criteria:

* 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

Primary outcomes:
measure: Phase 1: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
timeFrame: 2 years
measure: Phase 1: Number of participants with Dose-Limiting Toxicities (DLTs)
timeFrame: From first dose up to Day 28
measure: 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
timeFrame: 2 years
measure: Phase 2: Progression-free survival (PFS)
timeFrame: 2 years
Secondary outcomes:
measure: Phase 2: Number of participants with AEs and SAEs
timeFrame: 2 years
measure: Number of participants with AEs of special interests
timeFrame: 2 years
measure: Number of participants with OR per the Lugano Classification or IPCG criteria
timeFrame: 2 years
measure: Number of participants with OR per International workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria (DLBCL-RT [cohort 7] only
timeFrame: 2 years
measure: Number of participants with complete response (CR) per Lugano Classification or IPCG criteria for PCNSL
timeFrame: 2 years
measure: Duration of response (DOR)
timeFrame: 2 years
measure: Duration of complete response (DOCR)
timeFrame: 2 years
measure: Event-free survival (EFS)
timeFrame: 2 years
measure: Progression-free survival (PFS)
timeFrame: 2 years
measure: Overall survival (OS)
timeFrame: 2 years
measure: Number of participants without minimal Residual Disease (MRD) at CR (DLBCL, MCL and DLBCL-RT)
timeFrame: 2 years
measure: Pharmacokinetics (PK): Levels of anti-CD19 CAR T cells in blood at peak and over time
timeFrame: 2 years
measure: Pharmacodynamics (PD): Levels of chemokines in serum over time
timeFrame: Day 7 before infusion, Day 0, Day 1, Day 4, Day 7, Day 10, Day 14, Day 21, Day 28
measure: PD: Levels of cytokines in serum over time
timeFrame: Day 7 before infusion, Day 0, Day 1, Day 4, Day 7, Day 10, Day 14, Day 21, Day 28
measure: Percentage of successfully manufactured GLPG5101 products within the predefined release specifications
timeFrame: From leukapheresis to infusion
measure: 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
timeFrame: 2 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Edegem
country: Belgium
facility: Antwerp University Hospital
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liège
country: Belgium
facility: CHU De Liège
city: Woluwe-Saint-Lambert
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Study officials:
affiliation: Galapagos NV
name: Galapagos Study Director
role: STUDY_DIRECTOR
References: