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

Launched by ISTITUTO CLINICO HUMANITAS · Apr 2, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called Loncastuximab Tesirine for patients with Diffuse Large B-Cell Lymphoma (DLBCL) or High-Grade B-Cell Lymphoma (HGBCL) who have not responded to a previous treatment called CAR-T therapy. The main goal is to see if this new drug can help improve the patients' condition and how safe it is for them. Participants in the trial will receive the drug through an IV infusion every three weeks for up to eight cycles. They will also have regular check-ups, including scans and blood tests, to monitor their progress.

To be eligible for this trial, patients need to be at least 18 years old and have a confirmed diagnosis of DLBCL or HGBCL that has not improved after CAR-T therapy. They must also be able to give consent and have certain health conditions under control. Participants will be closely monitored for up to two years after their treatment to track how well the drug works and any side effects they may experience. This trial is important because it could provide new hope for patients with limited treatment options after CAR-T therapy.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Male or female patients aged ≥18 years.
• • 2. Ability to provide written informed consent.
• • 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• 4. 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.
• • 5. Measurable disease as defined by the Lugano 2014 Classification and confirmed by PET-CT, CT, or MRI scans, as appropriate.
• • 6. 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.
• • 7. Negative pregnancy test (β-HCG) for women of childbearing potential, performed within 7 days before the first dose of study drug (C1D1).
• • 8. 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.
• 9. 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.
• 10. Adequate hematologic function:
• • Absolute neutrophil count ≥1.0 × 10⁹/L. Hemoglobin ≥9.0 g/dL. Platelets ≥50 × 10⁹/L.
• Exclusion Criteria:
• • 1. Known hypersensitivity to Loncastuximab Tesirina or any component of the drug.
• • 2. Pregnant or breastfeeding women.
• • 3. 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.
• • 4. Active central nervous system (CNS) involvement, including leptomeningeal disease.
• • 5. Tumor mass with a diameter \>10 cm.
• • 6. Positive for HIV, hepatitis B (HBV), or hepatitis C (HCV) requiring antiviral treatment.
• • 7. Clinically significant third-space fluid accumulation (e.g., ascites or pleural effusion requiring drainage or associated with respiratory distress).
• • 8. 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.
• • 9. Active autoimmune disease, motor neuropathy of autoimmune origin, or other autoimmune diseases affecting the central nervous system (CNS).
• • 10. History of Stevens-Johnson syndrome or toxic epidermal necrolysis.
• • 11. Recent chemotherapy, radiotherapy, or other anticancer treatments (within 14 days prior to study drug administration, except if approved by the Sponsor).
• • 12. Planned administration of a live vaccine after the first dose of study drug (C1D1).
• • 13. Use of any experimental drug or therapy within 14 days before the first dose of study drug (C1D1).
• • 14. Failure to recover from prior chemotherapy or radiation-related toxicities to ≤Grade 1 (CTCAE v5.0) before screening.
• • 15. 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.