Treatment with Loncastuximab Tesirine for Lymphoma After CAR-T Therapy Failure

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This clinical trial evaluates the effectiveness and safety of Loncastuximab Tesirine in patients with relapsed or refractory Diffuse Large B-Cell Lymphoma (DLBCL) or High-Grade B-Cell Lymphoma (HGBCL) who have not responded to CAR-T therapy. It is a Phase II, single-arm trial that will enroll 50 participants, all receiving the same treatment regimen of intravenous infusions every three weeks for up to eight cycles. The primary focus is to assess the overall response rate (ORR) and monitor any potential side effects associated with the drug. Regular assessments will be conducted to evaluate treatment outcomes.

Why it matters

Who can join: the full rules

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.

Where it's running

• Azienda Ospedaliera Nazionale Santi Antonio e Biagio e Cesare Arrigo
  Alessandria, Alessandria, Italy Recruiting
• Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola
  Bologna, Bo, Italy Recruiting
• Azienda Sanitaria Ospedaliera Santa Croce e Carle di Cuneo
  Cuneo, Cuneo, Italy Recruiting
• Ospedale San Raffaele
  Milan, Milano, Italy Recruiting
• Istituto Nazionale dei Tumori
  Milan, Milano, Italy Recruiting
• Irccs Istituto Clinico Humanitas
  Rozzano, Milano, Italy Recruiting

Study contacts

• Study coordinator: Carmelo Carlo-Stella
• Email: carmelo.carlostella@hunimed.eu
• Phone: +39 02 8224 4577

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.