Study of Loncastuximab Tesirine in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) or High-Grade B-Cell Lymphoma (HGBCL) Following CAR-T Therapy Failure

Trial details

Who runs it

Istituto Clinico Humanitas

Trial code

NCT06918912EU 2024-516929-31-00

Record updated

2025. április 9.

Original description

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:Read full original descriptionShow less

Use of LOncastuximab Tesirine in Patients With RElapsed/Refractory Diffuse LargeB-Cell LYmphoma (DLBCL) or High Grade B-Cell Lymphoma (HGBCL) Who Have Progressive Disease After CAR T-cell Treatment

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.

Inclusion: Male or female patients aged ≥18 years; Ability to provide written informed consent; Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2; Histologically confirmed diagnosis of one of the following:; 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; Relapsed/refractory disease after prior CAR-T therapy, defined as:; Progressive disease (PD) at any time following CAR-T infusion. Partial response (PR) or stable disease (SD) at 3 months post-CAR-T infusion; Measurable disease as defined by the Lugano 2014 Classification and confirmed by PET-CT, CT, or MRI scans, as appropriate; Previous treatment with Loncastuximab Tesirina is allowed if the patient was in complete response (CR) or partial response (PR) at the time of discontinuation of the drug; Negative pregnancy test (β-HCG) for women of childbearing potential, performed within 7 days before the first dose of study drug (C1D1); Female patients of childbearing potential must agree to use highly effective contraception from the time of informed consent until at least 9 months after the last dose of Loncastuximab Tesirina. Male patients with female partners of childbearing potential must agree to use highly effective contraception from the time of informed consent until at least 6 months after the last dose of Loncastuximab Tesirina; Adequate renal, hepatic, pulmonary, and cardiac function:; Creatinine clearance ≥40 mL/min. ALT/AST ≤2.5 x ULN. Total bilirubin ≤1.5 x ULN (except for patients with Gilbert's syndrome). LVEF ≥50% (or center-specific lower limit). Oxygen saturation >92% at rest and no dyspnea >Grade 1; Adequate hematologic function:; Absolute neutrophil count ≥1.0 × 10⁹/L. Hemoglobin ≥9.0 g/dL. Platelets ≥50 × 10⁹/L.

Exclusion: Significant comorbid conditions, including uncontrolled hypertension (BP ≥160/100 mmHg), unstable angina, congestive heart failure (NYHA class III or IV), recent myocardial infarction or angioplasty within 6 months prior to screening, uncontrolled arrhythmia, poorly controlled diabetes, or severe chronic lung disease; Recent chemotherapy, radiotherapy, or other anticancer treatments (within 14 days prior to study drug administration, except if approved by the Sponsor); Planned administration of a live vaccine after the first dose of study drug (C1D1); Use of any experimental drug or therapy within 14 days before the first dose of study drug (C1D1); Failure to recover from prior chemotherapy or radiation-related toxicities to ≤Grade 1 (CTCAE v5.0) before screening; Known hypersensitivity to Loncastuximab Tesirina or any component of the drug; 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; Positive for HIV, hepatitis B (HBV), or hepatitis C (HCV) requiring antiviral treatment; Active autoimmune disease, motor neuropathy of autoimmune origin, or other autoimmune diseases affecting the central nervous system (CNS); History of Stevens-Johnson syndrome or toxic epidermal necrolysis; Any other disease, anomaly, or medical condition that, in the opinion of the investigator, would make the patient unsuitable for participation in the study or pose a risk to the patient; Pregnant or breastfeeding women; Tumor mass with a diameter >10 cm; Clinically significant third-space fluid accumulation (e.g., ascites or pleural effusion requiring drainage or associated with respiratory distress).

ClinicalTrials.gov NCT06918912 · EU CTIS 2024-516929-31-00