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

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

This study is testing if a new treatment called Loncastuximab Tesirine can help people with lymphoma who didn't get better after CAR-T therapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years to 99 Years
• Sex: All
• Sponsor: Istituto Clinico Humanitas (Academic / other)
• Drugs / interventions: Loncastuximab, CAR-T, chemotherapy, radiation
• Locations: 7 sites (Alessandria, ALESSANDRIA and 6 other locations)
• Trial ID: NCT06918912 on ClinicalTrials.gov

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.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with relapsed or refractory DLBCL or HGBCL following CAR-T therapy.

Not a fit: Patients who have not been diagnosed with DLBCL or HGBCL or those who have not undergone CAR-T therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with aggressive lymphomas who have exhausted other treatment avenues.

How similar studies have performed: While this approach is novel for this specific patient population, similar antibody-drug conjugates have shown promise in other studies.

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.

Where this trial is running

Alessandria, ALESSANDRIA and 6 other locations

• 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)
• AOU Policlinico Umberto I — Roma, Ro, Italy (Recruiting)

Study contacts

• Study coordinator: Carmelo Carlo-Stella

Conditions Diffuse Large B-Cell Lymphoma; High-grade B-cell Lymphoma; B-Cell Lymphoma Treatment; Relapsed or Refractory Lymphoma; Antibody-Drug Conjugates; Loncastuximab Tesirine