The goal of this clinical trial is to evaluate whether the drug Loncastuximab Tesirine can treat patients with relapsed or refractory Diffuse Large B-Cell Lymphoma (DLBCL) or High-Grade B-Cell Lymphoma (HGBCL) who have not responded to or have had a relapse after CAR-T therapy. The main question it aims to answer is:
* Can Loncastuximab Tesirine improve the overall response rate (ORR) in patients who have failed CAR-T therapy? * What are the safety and potential side effects of Loncastuximab Tesirine in this patient group?
This is a single-arm clinical trial, meaning all participants will receive the same treatment and there will be no comparison group. Researchers will focus on evaluating the effectiveness of the drug in helping patients achieve a response to treatment, and they will also assess the safety of the treatment.
Participants will:
* Be treated with Loncastuximab Tesirine through an intravenous (IV) infusion every 3 weeks for up to 8 cycles. * Undergo regular assessments to monitor the response to treatment, including PET-CT scans and blood tests to check for markers of the disease. * Be asked to provide informed consent before beginning the study and agree to follow the study procedures, including having biopsies performed to analyze biomarkers before starting treatment. * Be followed for up to 2 years after completing the treatment to track their progress and response.
This study aims to help doctors understand if Loncastuximab Tesirine can offer a new treatment option for patients who have not responded to CAR-T therapy and have limited options for further treatment. The trial will also provide more information on how to manage the safety of this treatment for these patients.
Male or female patients aged ≥18 years.
Ability to provide written informed consent.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
Diffuse large B-cell lymphoma (DLBCL), non-Hodgkin lymphoma, or high grade B-cell lymphoma (HGBCL), including double/triple-hit lymphomas with MYC, BCL2, and/or BCL6 rearrangements.
Known hypersensitivity to Loncastuximab Tesirina or any component of the drug.
Pregnant or breastfeeding women.
Active second primary malignancy, except for skin cancer, non-metastatic prostate cancer, cervical carcinoma in situ, ductal or lobular carcinoma in situ of the breast, or other malignancies that are considered not to interfere with the study by the investigator.
Active central nervous system (CNS) involvement, including leptomeningeal disease.
Single group
Loncastuximab Tesirine (Anti-CD19 Antibody-Drug Conjugate)
DrugLoncastuximab Tesirine is an antibody-drug conjugate specifically targeting CD19, a protein found on the surface of B-cells. It is designed to deliver a cytotoxic pyrrolobenzodiazepine dimer directly to CD19-expressing malignant B-cells. Unlike traditional chemotherapies, Loncastuximab Tesirine combines the precision of an anti-CD19 monoclonal antibody with a potent chemotherapy agent, offering targeted therapy for relapsed or refractory Diffuse Large B-Cell Lymphoma (DLBCL) and High-Grade B-Cell Lymphoma (HGBCL) after failure of CAR-T therapy. It is administered intravenously every 3 weeks, with an initial higher dose of 150 μg/kg followed by a reduced dose of 75 μg/kg for up to 8 cycles, distinguishing it from other treatments by its specific targeting mechanism and dosage regimen tailored to this patient population.
Overall Response Rate (ORR) in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) or High-Grade B-Cell Lymphoma (HGBCL) Following Failure of CAR-T Therapy After Treatment with Loncastuximab Tesirine
The primary outcome measure, Overall Response Rate (ORR), is defined as the proportion of patients who achieve either a Complete Response (CR) or Partial Response (PR) to treatment with Loncastuximab Tesirine, as assessed by independent central review using the 2014 Lugano Classification criteria. CR is defined as the complete disappearance of all measurable disease, while PR indicates a significant reduction in tumor size. ORR is evaluated at several time points: 6 weeks after Cycle 1 Day 1 (each cycle is 28 days), before Cycle 3 Day 1 (C3D1), and until study treatment completion, an average of 6 months.
Efficacy of Loncastuximab Tesirina in Relapsed/Refractory DLBCL or HGBCL Patients Post-CAR-T: Secondary Outcome Measure of Progression-Free Survival (PFS)
Progression-Free Survival (PFS): PFS is defined as the time from the first administration of the study drug to the first documented progression of disease (based on central review) or death from any cause. It is used to evaluate the duration of time patients remain free from disease progression while receiving treatment with loncastuximab tesirina. The metric is essential for assessing the long-term efficacy of the treatment and provides insight into the ability of loncastuximab tesirina to control disease progression after the failure of CAR-T therapy.
Exploratory Endpoints: Evaluation of Serum Disease and Inflammation Markers, and Correlation Between Clinical Activity and ctDNA Changes in Relapsed/Refractory DLBCL or HGBCL Patients Post-CAR-T Treatment with Loncastuximab Tesirina. CRP Levels
The study will assess changes in serum CRP levels to explore their relationship with clinical activity, as measured by ORR. The correlation between CRP levels and clinical activity will be explored.
Exploratory Endpoints: Evaluation of Serum Disease and Inflammation Markers, and Correlation Between Clinical Activity and ctDNA Changes in Relapsed/Refractory DLBCL or HGBCL Patients Post-CAR-T Treatment with Loncastuximab Tesirina. LDH Levels.
The study will assess changes in serum LDH levels to explore their relationship with clinical activity, as measured by Objective Response Rate (ORR). The correlation between LDH levels and clinical activity will be explored.
Exploratory Endpoints: Evaluation of Serum Disease and Inflammation Markers, and Correlation Between Clinical Activity and ctDNA Changes in Relapsed/Refractory DLBCL or HGBCL Patients Post-CAR-T Treatment with Loncastuximab Tesirina. Ferritin Levels.
The study will assess changes in serum ferritin levels to explore their relationship with clinical activity, as measured by ORR. The correlation between ferritin levels and clinical activity will be explored.
Exploratory Endpoints: Evaluation of Serum Disease and Inflammation Markers, and Correlation Between Clinical Activity and ctDNA Changes in Relapsed/Refractory DLBCL or HGBCL Patients Post-CAR-T Treatment with Loncastuximab Tesirina. ctDNA Levels
The study will assess changes in ctDNA levels to explore their relationship with clinical activity, as measured by ORR. The correlation between ctDNA levels and clinical activity will be explored. Units of Measure: ng/mL or copies per mL (depending on the assay used).
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