A Study Evaluating the Safety and Efficacy of GLPG5101 (19CP02) in Participants With Non-Hodgkin Lymphoma

Phase 1

Recruiting

• Conditions: Lymphomas Non-Hodgkin's B-cell; Relapsed/Refractory B-cell Non-Hodgkin Lymphoma
• 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 dose of GLPG5101 works best with the least number of side effects.

* In the second phase, all participants will get the best dose of the first phase.

Detailed Description

Phase 1 Dose escalation phase:

The dose escalation phase is designed to select the optimal dose based on efficacy and safety outcomes.

Three dose levels of GLPG5101 will be evaluated to determine the recommended phase 2 dose (RP2D).

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 aggressive Diffuse large B-cell lymphoma (DLBCL) will be enrolled.

Phase 2 Dose expansion phase:

After completion of the dose escalation phase, the dose expansion phase of the study will proceed per sponsor decision.

During this phase of the study, participants will be enrolled into separate disease cohorts as defined by their NHL subtype:

1. DLBCL

2. High-risk DLBCL

3. FL and MZL

4. MCL

5. Burkitt lymphoma (BL)

6. Primary central nervous system lymphoma (PCNSL)

Participants per disease cohort will be treated at the RP2D.

Study Timeline

• Study Start: 2022-03-09
• Status Verified: 2024-08
• Study First Submitted: 2024-08-16
• Study First Submitted QC: 2024-08-16
• Last Update Submitted: 2024-08-16
• Study First Posted: 2024-08-20
• Last Update Posted: 2024-08-20
• Primary Completion: 2029-05-31
• Study Completion: 2029-05-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 195

Inclusion Criteria

• Histologically confirmed diagnosis of one of the following NHL subtypes: Aggressive DLBCL, FL grade 1, 2 or 3A, MZL, or MCL, BL, PCNSL
• Relapsed or refractory disease
• Measurable disease according to the Lugano classification or IPCG criteria for PCNSL
• 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

Key

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Exclusion Criteria

• Richter's transformation
• 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)
• Active central nervous system (CNS) involvement (with neurological changes) by disease under study (exceptions per protocol)
• Infection with human immunodeficiency virus (HIV), active hepatitis B or active hepatitis C virus

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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 Dose-Limiting Toxicities (DLTs)	From first dose up to Day 28
Phase 1: Number of participants with adverse events (AEs) and serious adverse events (SAEs)	2 years
Phase 2: Number of participants with best objective response (OR) per the Lugano Classification or International Primary central nervous system lymphoma Collaborative Group (IPCG) criteria	2 years

Secondary Outcome Measures

Name	Time	Method
PK: Levels of anti-CD19 CAR T cells in bone marrow	2 years
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 metabolic complete response (mCR)	2 years
Duration of response (DOR)	2 years
Progression-free survival (PFS)	2 years
Overall survival (OS)	2 years
Event-free survival (EFS)	2 years
Number of participants with best OR per the Lugano Classification or IPCG criteria	2 years
Number of participants without minimal Residual Disease (MRD)	2 years
Pharmacokinetics (PK): Levels of anti-CD19 CAR T cells in blood	2 years
PK: Levels of anti-CD19 CAR T cells in cerebrospinal fluid (CSF)	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

Trial Locations

Locations (9)

Beth Israel Deaconess Medical Center Clinical Laboratories; 🇺🇸 Boston, Massachusetts, United States

Academisch Medisch Centrum; 🇳🇱 Amsterdam, Netherlands

Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States

UZ Leuven; 🇧🇪 Leuven, Belgium

CHU De Liège; 🇧🇪 Liège, Belgium

Cliniques Universitaires Saint-Luc; 🇧🇪 Woluwe-Saint-Lambert, Belgium

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC); 🇳🇱 Rotterdam, Netherlands

Antwerp University Hospital; 🇧🇪 Edegem, Belgium