Long-term Safety Evaluation of BCN-CP01, 19CP02, and BCMACP03 in Patients with Relapsed/Refractory CLL, SLL, B-Cell NHL, or Multiple Myeloma

The primary objective of this study is to evaluate the long-term **safety** of GLPG CAR T-cell products for up to 15 years following CAR T-cell product infusion. This is clinically relevant as it aims to ensure the sustained safety of these advanced therapies in patients with relapsed or refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL), relapsed/refractory B-Cell non-Hodgkin lymphoma, and relapsed/refractory multiple myeloma. Monitoring long-term safety is crucial for understanding potential late-onset adverse effects and ensuring patient well-being over an extended period.

Secondary objectives include evaluating the long-term efficacy of GLPG CAR T-cell products for up to 15 years post-infusion. This assessment is important to determine the sustained therapeutic benefits and potential for long-term remission in patients receiving these treatments.

The clinical trial involves participants diagnosed with **relapsed or refractory Chronic Lymphocytic Leukemia (CLL)**, Small Lymphocytic Lymphoma (SLL), relapsed/refractory B-Cell non-Hodgkin lymphoma, or relapsed/refractory multiple myeloma. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. The trial population was selected based on their previous treatment with GLPG CAR T-cell therapy in a clinical trial or Managed Access Program. Participants are required to be able and willing to comply with the clinical study protocol requirements and must have signed and dated the informed consent form as approved by the Independent Ethics Committee or Institutional Review Board. The sponsor has not provided the total number of participants. The study includes a vulnerable population, indicating that special considerations are in place to ensure their safety and ethical treatment throughout the trial. Lifestyle factors such as diet, physical activity, and habits are not specified in the available data.

The clinical trial is designed to evaluate the long-term safety of **CAR T-cell therapies** in patients with relapsed or refractory **Chronic Lymphocytic Leukemia (CLL)**, Small Lymphocytic Lymphoma (SLL), B-Cell non-Hodgkin lymphoma, and multiple myeloma. This is a Phase III, randomized, double-blind, controlled study with an estimated duration extending up to 15 years post-infusion of the CAR T-cell product. The trial will commence with a screening visit to confirm eligibility based on the inclusion criteria, which require participants to have been previously treated with a GLPG CAR T-cell therapy in a clinical trial or Managed Access Program. Participants must also provide informed consent prior to any study-related procedures.

Following the screening, participants will undergo a series of study visits, including regular follow-up visits to monitor the incidence of adverse events, serious adverse events, and the presence of CAR transgene levels in peripheral blood. The primary endpoints focus on the type and incidence of targeted adverse events, serious adverse events related to the therapy, and the detection of replication-competent lentivirus. Secondary endpoints include disease progression status, time to subsequent anticancer therapy, and overall survival. The end-of-study visit will conclude the participant's involvement, assessing the long-term safety outcomes and any late-onset adverse effects.

Participant involvement is expected to last for the entire duration of the study, up to 15 years, unless early termination is warranted. Conditions for early termination include withdrawal of consent, non-compliance with the study protocol, or the occurrence of significant adverse events that necessitate discontinuation. The trial aims to provide comprehensive safety data on the long-term effects of CAR T-cell therapies, contributing valuable insights into their use in treating these hematological malignancies.

The clinical trial involves the administration of three experimental medications, each formulated as a **dispersion for infusion**. The first medication, BCN-CP01, is a cell therapy product developed by CELLPOINT B.V. It is administered via **intravenous use** with a maximum daily dose of 300 Miu iu (1,000,000s) and a total dose not exceeding 300 Miu iu over a treatment period of one day. BCN-CP01 is a genetically modified organism (GMO) product, specifically targeting the CD19 gene, and is derived from T cells using a lentivirus vector. Participant compliance with the dosing schedule is monitored throughout the trial.

The second experimental medication, 19CP02, also developed by CELLPOINT B.V., is administered as a **dispersion for infusion** through **intravenous use**. The maximum daily and total dose for 19CP02 is 250 Munit million units, with the treatment period limited to one day. This cell therapy product is a GMO, utilizing an anti-CD19 CAR gene of interest, and is similarly derived from T cells using a lentivirus vector. Compliance with the dosing regimen is closely monitored to ensure adherence to the protocol.

The third medication, BCMACP03, is another cell therapy product from CELLPOINT B.V., provided as a **dispersion for infusion** and administered via **intravenous infusion**. The dosing schedule allows for a maximum daily and total dose of 300 Miu iu (1,000,000s) over a one-day treatment period. BCMACP03 is a GMO product, derived from T cells and utilizing a lentivirus vector. Participant adherence to the dosing schedule is systematically monitored to maintain protocol compliance.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are utilized in this study. The trial focuses solely on the evaluation of the experimental medications mentioned above.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints include the type and incidence of targeted adverse events (AEs), the type and incidence of serious AEs (SAEs) related to the GLPG CAR T-cell therapy, the incidence of detectable CAR transgene levels in peripheral blood, the pattern of vector integration sites if at least 1% of T-cells in the blood sample or new malignancies are positive for vector sequences, the incidence of detectable replication-competent lentivirus (RCL) in peripheral blood, and the cause of death. These parameters will be measured to evaluate the long-term safety of the GLPG CAR T-cell products.

Secondary endpoints will focus on disease progression status, time to subsequent anticancer therapy, and overall survival. These efficacy parameters will be collected and analyzed over the course of the study, which is designed to follow patients for up to 15 years post-CAR T-cell product infusion. The study will utilize various tools and methods to ensure accurate and reliable data collection, although specific instruments are not detailed in the provided information. The trial is categorized as a Phase III study, indicating a focus on confirming efficacy and monitoring adverse reactions in a larger patient population.