Diffuse Large B-Cell LymphomaPhase 2LORELYNCT06918912
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
A Phase 2 study testing Loncastuximab Tesirine (Anti-CD19 Antibody-Drug Conjugate) in people with Diffuse Large B-Cell Lymphoma and High-grade B-cell Lymphoma (HGBCL), run by Istituto Clinico Humanitas at 7 sites in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Diffuse Large B-Cell Lymphoma, High-grade B-cell Lymphoma (HGBCL), B-Cell Lymphoma Treatment
- What is being tested?
- Loncastuximab Tesirine (Anti-CD19 Antibody-Drug Conjugate)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 7 sitesItaly
- Study dates
- 16 Jun 2023to Jun 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
7 sites in 1 country. Contact the study team or a site near you to ask about taking part.
7 sites in 1 country
Italy7 sites, 7 recruiting
- Recruiting
Azienda Ospedaliera Nazionale Santi Antonio e Biagio e Cesare Arrigo
Alessandria, ALESSANDRIA, 15121
MARCO LADETTO, marco.ladetto@ospedale.al.it
- Recruiting
Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola
Bologna, BO, 40138
Pier Luigi Zinzani, pierluigi.zinzani@unibo.it
- Recruiting
Azienda Sanitaria Ospedaliera Santa Croce e Carle di Cuneo
Cuneo, Cuneo, 12100
Alessia Castellino, castellino.ale@ospedale.cuneo
- Recruiting
Ospedale San Raffaele
Milan, MILANO, 20132
Ferreri Andrés José Maria, ferreri.andres@hsr.it
- Recruiting
Istituto Nazionale dei Tumori
Milan, MILANO, 20133
Paolo Corradini, +39 02 23903408, paolo.corradini@istitutotumori.mi.it
- Recruiting
AOU Policlinico Umberto I
Roma, RO, 00161
Alice Di Rocco, dirocco@bce.uniroma1.it
- Recruiting
Irccs Istituto Clinico Humanitas
Rozzano, MILANO, 20089
Carmelo Carlo-Stella, +39 02 8224 4577, carmelo.carlostella@hunimed.eu
About this study
Official title: 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?
Read more
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.
Read the detailed description
The goal of this clinical trial is to evaluate the feasibility, safety, and efficacy 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 or have had a relapse following treatment with CAR-T therapy. This trial aims to assess whether Loncastuximab Tesirine can provide a viable therapeutic option for this patient population, particularly considering the urgent unmet medical need for new treatment options in cases where CAR-T therapy has failed.
Study Design: This study is a Phase II, multicenter, single-arm, prospective clinical trial. It will enroll a total of 50 patients diagnosed with DLBCL or HGBCL, who have experienced relapse or refractoriness after CAR-T therapy. The trial will focus on assessing the overall response rate (ORR), as well as the safety profile of the drug in this population.
Treatment Protocol: Loncastuximab Tesirine (also known as an antibody-drug conjugate or ADC) will be administered intravenously (IV) every three weeks for a total of up to 8 cycles, following the following dosing schedule:
150 μg/kg for the first two cycles (C1D1 and C2D1), 75 μg/kg starting from cycle 3 (C3D1) until the completion of the treatment. The drug will be infused over a 30-minute period. Patients will be closely monitored for adverse events during each infusion, and the dosage will be adjusted as needed based on safety and tolerability.
Study Objectives: The primary objective of this clinical trial is to evaluate the efficacy of Loncastuximab Tesirine in patients with relapsed or refractory DLBCL or HGBCL who have not responded to CAR-T therapy, as measured by the overall response rate (ORR). The secondary objectives of the study are to assess progression-free survival (PFS), overall survival (OS), and duration of response (DOR). Additionally, the trial will focus on the safety and tolerability of the drug, as well as exploring the relationship between biomarkers and clinical outcomes.
The primary hypotheses to be tested in this trial are:
The ORR for patients treated with Loncastuximab Tesirine is greater than 30%, with a goal of reaching 45%.
The treatment will be well-tolerated, with manageable side effects in this patient population.
The study will also investigate exploratory objectives, including the assessment of changes in disease markers (e.g., LDH, CRP, ferritin) and their correlation with clinical outcomes, as well as exploring changes in circulating tumor DNA (ctDNA) as a potential biomarker of treatment response.
Eligibility and Enrollment: Eligible participants will be adults aged 18 years or older who have been diagnosed with relapsed or refractory DLBCL or HGBCL, and who have not responded to or have relapsed after CAR-T therapy. Detailed criteria for inclusion and exclusion are outlined in the study's protocol, which focuses on ensuring that participants are in an appropriate health condition to receive the treatment and can be closely monitored for the duration of the study.
Informed Consent and Screening: Before beginning the treatment, all participants must provide written informed consent. Screening will involve a series of assessments, including a review of the patient's medical history, laboratory tests, imaging studies (such as PET-CT or CT scans), and biomarker analysis to ensure they meet the eligibility criteria.
In particular, a biopsy of the tumor tissue will be required before enrollment for biomarker analysis, and tests such as a negative pregnancy test will be mandatory for women of childbearing age. Participants will also need to have adequate organ function and a performance status (ECOG) between 0 and 2.
Study Procedures:
Initial Assessment (Screening): Participants will undergo a screening period during which baseline assessments are conducted. This includes a full medical history review, laboratory tests (such as blood counts, liver and kidney function tests), imaging studies (such as PET-CT scans), and the collection of tumor tissue samples for biomarker analysis.
Treatment Cycle: The treatment will involve administration of Loncastuximab Tesirine via intravenous infusion every 21 days (three-week intervals) for up to 8 cycles. Each infusion will be monitored for potential allergic reactions and adverse effects. Patients will be closely observed for 30 minutes following the infusion, and any adverse reactions will be managed as appropriate. Patients will also have regular clinical evaluations, including blood work, to monitor for treatment-related toxicities.
Response Evaluation: The effectiveness of the treatment will be evaluated based on changes in the size of the tumor as determined by imaging studies (PET-CT or CT scans). This will be performed at various timepoints: after Cycle 1 Day 1 (C1D1), before Cycle 3 Day 1 (C3D1), and at the end of treatment (EOT). Tumor response will be categorized as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) according to the Lugano Classification (2014).
Post-Treatment Follow-Up: After completing the treatment cycles, patients will be followed up for 2 years. Follow-up visits will include imaging (PET-CT or CT scans) and laboratory tests to monitor disease progression, as well as assessment of any long-term treatment-related side effects.
Safety Monitoring: The safety of the treatment will be closely monitored throughout the study. Vital signs, physical exams, and performance status (ECOG PS) will be assessed regularly. Blood tests will be conducted to monitor organ function (liver, kidney) and the hematologic profile (complete blood count, liver enzymes, renal function markers). The occurrence of adverse events (AE) and serious adverse events (SAE) will be recorded, and the severity of AEs will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0).
Statistical Analysis: The study is designed to assess the efficacy of Loncastuximab Tesirine in this specific population. The sample size of 50 patients was chosen to provide sufficient statistical power to detect a significant response rate. The primary endpoint, the overall response rate (ORR), will be calculated as the proportion of patients who achieve a complete or partial response. A target ORR of 45% is considered clinically relevant, while an ORR below 30% would suggest that the treatment is not effective.
The secondary endpoints, including progression-free survival (PFS), overall survival (OS), and duration of response (DOR), will be analyzed using the Kaplan-Meier method. Differences between subgroups will be assessed using the log-rank test, and Cox regression analysis will be performed to estimate hazard ratios for survival outcomes.
The safety data will be summarized descriptively, including the frequency and severity of adverse events. The frequency of adverse events will be compared between different subgroups to identify potential risk factors for toxicity.
Exploratory Analyses: The exploratory objectives of the study include evaluating biomarkers that may help predict treatment response, such as changes in serum markers (LDH, CRP, ferritin) and the analysis of circulating tumor DNA (ctDNA). These exploratory analyses will help establish potential biomarkers for monitoring treatment response and could guide future studies on the mechanism of action of Loncastuximab Tesirine in patients with relapsed/refractory DLBCL or HGBCL.
Expected Outcomes: The study is expected to provide valuable information on the efficacy and safety of Loncastuximab Tesirine in patients with relapsed or refractory DLBCL or HGBCL who have failed CAR-T therapy. If the treatment demonstrates a significant response rate and manageable safety profile, it could potentially become a new therapeutic option for this challenging patient population.
Furthermore, the exploratory analyses of biomarkers and ctDNA will offer insights into the molecular mechanisms behind treatment response and resistance, which could be crucial for the development of personalized treatment strategies in the future.
Study Timeline:
Study Initiation: Approximately 1 month after approval by the Ethics Committee. Enrollment Period: Expected to last for 18 months, with the first patient expected to begin treatment shortly after Ethics Committee approval.
Follow-Up Period: Patients will be followed for up to 2 years after the completion of the last treatment cycle.
Data Analysis: Data analysis is expected to be completed within 3 months following the last patient's final visit, and the final study report will be available within 10-12 months.
- Conditions
- Diffuse Large B-Cell Lymphoma, High-grade B-cell Lymphoma (HGBCL), B-Cell Lymphoma Treatment, Relapsed or Refractory Lymphoma
- Being tested
- Loncastuximab Tesirine (Anti-CD19 Antibody-Drug Conjugate)
- Keywords
- Antibody-Drug Conjugates, Loncastuximab Tesirine
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Recurrence, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Loncastuximab Tesirine (Anti-CD19 Antibody-Drug Conjugate) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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): PFS is defined as the time from the first administration of the study drug to the first documented progression of disease (based on central review) or death from any cause. It is used to evaluate the duration of time patients remain free from disease progression while receiving treatment with loncastuximab tesirina. The metric is essential for assessing the long-term efficacy of the treatment and provides insight into the ability of loncastuximab tesirina to control disease progression after the failure of CAR-T therapy.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2025
- Study start16 Jun 2023
- Primary completion4 Mar 2025
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Large B-Cell LymphomaStudies of the same condition, open and under way.
- More trials run by Istituto Clinico HumanitasThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Istituto Clinico Humanitas
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06918912
- Sponsor's protocol ID
- ONC-2021-001
- Other IDs
- 2024-516929-31-00, 2022-001147-24
- Acronym
- LORELY
- Status last verified
- Apr 2025
- First submitted
- 17 Mar 2025
- Last updated
- 9 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06918912
- Acronym / sponsor ID
- LORELY / ONC-2021-001
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Istituto Clinico HumanitasUniversity, hospital or other
- Study start
- 16 Jun 2023 (actual)
- Primary completion
- 4 Mar 2025 (actual)
- Study completion
- Jun 2027 (estimated)
- First posted
- 9 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The goal of this clinical trial is to evaluate the feasibility, safety, and efficacy 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 or have had a relapse following treatment with CAR-T therapy. This trial aims to assess whether Loncastuximab Tesirine can provide a viable therapeutic option for this patient population, particularly considering the urgent unmet medical need for new treatment options in cases where CAR-T therapy has failed.
Study Design: This study is a Phase II, multicenter, single-arm, prospective clinical trial. It will enroll a total of 50 patients diagnosed with DLBCL or HGBCL, who have experienced relapse or refractoriness after CAR-T therapy. The trial will focus on assessing the overall response rate (ORR), as well as the safety profile of the drug in this population.
Treatment Protocol: Loncastuximab Tesirine (also known as an antibody-drug conjugate or ADC) will be administered intravenously (IV) every three weeks for a total of up to 8 cycles, following the following dosing schedule:
150 μg/kg for the first two cycles (C1D1 and C2D1), 75 μg/kg starting from cycle 3 (C3D1) until the completion of the treatment. The drug will be infused over a 30-minute period. Patients will be closely monitored for adverse events during each infusion, and the dosage will be adjusted as needed based on safety and tolerability.
Study Objectives: The primary objective of this clinical trial is to evaluate the efficacy of Loncastuximab Tesirine in patients with relapsed or refractory DLBCL or HGBCL who have not responded to CAR-T therapy, as measured by the overall response rate (ORR). The secondary objectives of the study are to assess progression-free survival (PFS), overall survival (OS), and duration of response (DOR). Additionally, the trial will focus on the safety and tolerability of the drug, as well as exploring the relationship between biomarkers and clinical outcomes.
The primary hypotheses to be tested in this trial are:
The ORR for patients treated with Loncastuximab Tesirine is greater than 30%, with a goal of reaching 45%.
The treatment will be well-tolerated, with manageable side effects in this patient population.
The study will also investigate exploratory objectives, including the assessment of changes in disease markers (e.g., LDH, CRP, ferritin) and their correlation with clinical outcomes, as well as exploring changes in circulating tumor DNA (ctDNA) as a potential biomarker of treatment response.
Eligibility and Enrollment: Eligible participants will be adults aged 18 years or older who have been diagnosed with relapsed or refractory DLBCL or HGBCL, and who have not responded to or have relapsed after CAR-T therapy. Detailed criteria for inclusion and exclusion are outlined in the study's protocol, which focuses on ensuring that participants are in an appropriate health condition to receive the treatment and can be closely monitored for the duration of the study.
Informed Consent and Screening: Before beginning the treatment, all participants must provide written informed consent. Screening will involve a series of assessments, including a review of the patient's medical history, laboratory tests, imaging studies (such as PET-CT or CT scans), and biomarker analysis to ensure they meet the eligibility criteria.
In particular, a biopsy of the tumor tissue will be required before enrollment for biomarker analysis, and tests such as a negative pregnancy test will be mandatory for women of childbearing age. Participants will also need to have adequate organ function and a performance status (ECOG) between 0 and 2.
Study Procedures:
Initial Assessment (Screening): Participants will undergo a screening period during which baseline assessments are conducted. This includes a full medical history review, laboratory tests (such as blood counts, liver and kidney function tests), imaging studies (such as PET-CT scans), and the collection of tumor tissue samples for biomarker analysis.
Treatment Cycle: The treatment will involve administration of Loncastuximab Tesirine via intravenous infusion every 21 days (three-week intervals) for up to 8 cycles. Each infusion will be monitored for potential allergic reactions and adverse effects. Patients will be closely observed for 30 minutes following the infusion, and any adverse reactions will be managed as appropriate. Patients will also have regular clinical evaluations, including blood work, to monitor for treatment-related toxicities.
Response Evaluation: The effectiveness of the treatment will be evaluated based on changes in the size of the tumor as determined by imaging studies (PET-CT or CT scans). This will be performed at various timepoints: after Cycle 1 Day 1 (C1D1), before Cycle 3 Day 1 (C3D1), and at the end of treatment (EOT). Tumor response will be categorized as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) according to the Lugano Classification (2014).
Post-Treatment Follow-Up: After completing the treatment cycles, patients will be followed up for 2 years. Follow-up visits will include imaging (PET-CT or CT scans) and laboratory tests to monitor disease progression, as well as assessment of any long-term treatment-related side effects.
Safety Monitoring: The safety of the treatment will be closely monitored throughout the study. Vital signs, physical exams, and performance status (ECOG PS) will be assessed regularly. Blood tests will be conducted to monitor organ function (liver, kidney) and the hematologic profile (complete blood count, liver enzymes, renal function markers). The occurrence of adverse events (AE) and serious adverse events (SAE) will be recorded, and the severity of AEs will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0).
Statistical Analysis: The study is designed to assess the efficacy of Loncastuximab Tesirine in this specific population. The sample size of 50 patients was chosen to provide sufficient statistical power to detect a significant response rate. The primary endpoint, the overall response rate (ORR), will be calculated as the proportion of patients who achieve a complete or partial response. A target ORR of 45% is considered clinically relevant, while an ORR below 30% would suggest that the treatment is not effective.
The secondary endpoints, including progression-free survival (PFS), overall survival (OS), and duration of response (DOR), will be analyzed using the Kaplan-Meier method. Differences between subgroups will be assessed using the log-rank test, and Cox regression analysis will be performed to estimate hazard ratios for survival outcomes.
The safety data will be summarized descriptively, including the frequency and severity of adverse events. The frequency of adverse events will be compared between different subgroups to identify potential risk factors for toxicity.
Exploratory Analyses: The exploratory objectives of the study include evaluating biomarkers that may help predict treatment response, such as changes in serum markers (LDH, CRP, ferritin) and the analysis of circulating tumor DNA (ctDNA). These exploratory analyses will help establish potential biomarkers for monitoring treatment response and could guide future studies on the mechanism of action of Loncastuximab Tesirine in patients with relapsed/refractory DLBCL or HGBCL.
Expected Outcomes: The study is expected to provide valuable information on the efficacy and safety of Loncastuximab Tesirine in patients with relapsed or refractory DLBCL or HGBCL who have failed CAR-T therapy. If the treatment demonstrates a significant response rate and manageable safety profile, it could potentially become a new therapeutic option for this challenging patient population.
Furthermore, the exploratory analyses of biomarkers and ctDNA will offer insights into the molecular mechanisms behind treatment response and resistance, which could be crucial for the development of personalized treatment strategies in the future.
Study Timeline:
Study Initiation: Approximately 1 month after approval by the Ethics Committee. Enrollment Period: Expected to last for 18 months, with the first patient expected to begin treatment shortly after Ethics Committee approval.
Follow-Up Period: Patients will be followed for up to 2 years after the completion of the last treatment cycle.
Data Analysis: Data analysis is expected to be completed within 3 months following the last patient's final visit, and the final study report will be available within 10-12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment with Loncastuximab Tesirine in Relapsed/Refractory DLBCL or HGBCL after CAR-T Failure | Experimental | Drug: Loncastuximab Tesirine (Anti-CD19 Antibody-Drug Conjugate)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. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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:
- Progressive disease (PD) at any time following CAR-T infusion. Partial response (PR) or stable disease (SD) at 3 months post-CAR-T infusion.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Loncastuximab Tesirine (Anti-CD19 Antibody-Drug Conjugate)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. | Drug | Treatment with Loncastuximab Tesirine in Relapsed/Refractory DLBCL or HGBCL after CAR-T Failure |
Primary outcome
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
Time frame: 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.
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.
1 secondary outcome
Efficacy of Loncastuximab Tesirina in Relapsed/Refractory DLBCL or HGBCL Patients Post-CAR-T: Secondary Outcome Measure of Progression-Free Survival (PFS)
Time frame: 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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Loncastuximab Tesirine (Anti-CD19 Antibody-Drug Conjugate) in people with Diffuse Large B-Cell Lymphoma and High-grade B-cell Lymphoma (HGBCL), run by Istituto Clinico Humanitas at 7 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Carmelo Carlo-Stella (+39 02 8224 4577, carmelo.carlostella@hunimed.eu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2025.