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

NCT06918912 | Recruiting Phase 2

• 3 other identifiers: ONC-2021-0012024-516929-31-002022-001147-24
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Diffuse Large B-Cell Lymphoma; High-grade B-cell Lymphoma (HGBCL); B-Cell Lymphoma Treatment; Relapsed or Refractory Lymphoma

Keywords

Antibody-Drug Conjugates; Loncastuximab Tesirine

Outcome Measures

Primary Outcomes (1)

• 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.

  The Overall Response Rate will be assessed at three key time points: 6 weeks after C1D1 (each cycle is 28 days), before C3D1, and at the end of treatment an average of 6 months. These assessments will evaluate the best OR to Loncastuximab Tesirine.

Secondary Outcomes (1)

• 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) will be assessed at 6 weeks after C1D1, before C3D1, and at study treatment completion (an average of 6 months)), with subsequent follow-up every 3 months for 2 years to monitor disease progression or death.

Other Outcomes (4)

• 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

  CRP (mg/L) will be assessed at baseline, after C1D1, before C3D1, and at the EOT (after about six months), with follow-up evaluations every 3 months during the 2-year monitoring period.

• 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.

  LDH (U/L ) will be assessed at baseline, after C1D1, before Cycle C3D1, and at the EOT( after about six months), with follow-up evaluations every 3 months during the 2-year monitoring period.

• 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.

  Ferritin (ng/mL) will be assessed at baseline, after C1D1, before C3D1, and at the EOT (after about six months), with follow-up evaluations every 3 months during the 2-year monitoring period.

Study Arms (1)

Treatment with Loncastuximab Tesirine in Relapsed/Refractory DLBCL or HGBCL after CAR-T Failure

EXPERIMENTAL

This arm of the study involves the administration of Loncastuximab Tesirine to patients with relapsed or refractory Diffuse Large B-Cell Lymphoma (DLBCL) or High-Grade B-Cell Lymphoma (HGBCL) who have failed prior treatment with CAR-T therapy. Participants will receive an intravenous infusion of Loncastuximab Tesirine at a dose of 150 μg/kg for the first two cycles, followed by 75 μg/kg for up to 6 additional cycles, totaling 8 cycles of treatment. The drug will be administered every 3 weeks. The primary goal is to evaluate the treatment's efficacy, as well as its safety, by monitoring response rates, progression-free survival, and overall survival, along with potential adverse events. Participants will be followed for 24 months after the end of treatment.

Drug: Loncastuximab Tesirine (Anti-CD19 Antibody-Drug Conjugate)

Interventions

Loncastuximab Tesirine (Anti-CD19 Antibody-Drug Conjugate) DRUG

Loncastuximab 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.

Treatment with Loncastuximab Tesirine in Relapsed/Refractory DLBCL or HGBCL after CAR-T Failure

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Tumor mass with a diameter \>10 cm.
• Positive for HIV, hepatitis B (HBV), or hepatitis C (HCV) requiring antiviral treatment.
• Clinically significant third-space fluid accumulation (e.g., ascites or pleural effusion requiring drainage or associated with respiratory distress).
• 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.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Istituto Clinico Humanitas: lead

Study Sites (7)

Azienda Ospedaliera Nazionale Santi Antonio e Biagio e Cesare Arrigo

Alessandria, ALESSANDRIA, 15121, Italy

RECRUITING

Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola

Bologna, BO, 40138, Italy

RECRUITING

Azienda Sanitaria Ospedaliera Santa Croce e Carle di Cuneo

Cuneo, Cuneo, 12100, Italy

RECRUITING

Ospedale San Raffaele

Milan, MILANO, 20132, Italy

RECRUITING

Istituto Nazionale dei Tumori

Milan, MILANO, 20133, Italy

RECRUITING

Irccs Istituto Clinico Humanitas

Rozzano, MILANO, 20089, Italy

RECRUITING

AOU Policlinico Umberto I

Roma, RO, 00161, Italy

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Recurrence; Lymphoma

Interventions

loncastuximab tesirine

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Carmelo Carlo-Stella

CONTACT

+39 02 8224 4577; carmelo.carlostella@hunimed.eu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2025
• First Posted: April 9, 2025
• Study Start: June 16, 2023
• Primary Completion: March 4, 2025
• Study Completion (Estimated): June 1, 2027
• Last Updated: April 9, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (7)