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Consolidation therapy with loncastuximab tesirine for relapsed or refractory mantle cell lymphoma patients

Consolidation With ADCT-402 (Loncastuximab Tesirine) After a Short Course of Immunochemotherapy: a Phase II Study in BTKi-treated (or BTKi Intolerant) Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL) Patients

Phase 2 Interventional Fondazione Italiana Linfomi - ETS · NCT05249959

This study is testing if a new treatment called loncastuximab tesirine can help patients with relapsed or hard-to-treat mantle cell lymphoma stay in remission after receiving other therapies.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment49 (estimated)
Ages18 Years to 79 Years
SexAll
SponsorFondazione Italiana Linfomi - ETS Academic / other
Drugs / interventionsloncastuximab, CAR-T, chemotherapy, immunotherapy, Rituximab, prednisone
Locations21 sites (Brescia, Italy and 20 other locations)
Trial IDNCT05249959 on ClinicalTrials.gov

What this trial studies

This phase 2, multicenter, open-label, single-arm study evaluates the efficacy and safety of loncastuximab tesirine as a consolidation therapy following salvage immunochemotherapy in patients with relapsed or refractory mantle cell lymphoma who have been treated with or are intolerant to Bruton Tyrosine Kinase inhibitors. Participants will receive two courses of Rituximab-Bendamustine-Cytarabine (R-BAC) before undergoing consolidation with loncastuximab tesirine. The study aims to assess the rate of minimal residual disease negativity and the overall safety profile of the treatment.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 to 85 with relapsed or refractory mantle cell lymphoma who have previously been treated with Bruton Tyrosine Kinase inhibitors.

Not a fit: Patients who have not been previously treated with Bruton Tyrosine Kinase inhibitors or those with other types of lymphoma may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve outcomes for patients with difficult-to-treat relapsed or refractory mantle cell lymphoma.

How similar studies have performed: Other studies have shown promising results with similar consolidation therapies in hematological malignancies, suggesting potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Histologically documented diagnosis of MCL as defined in the 2017 edition of the World Health Organization (WHO) classification
* Age ≥ 18 and \< 85 years
* Relapsed/Refractory disease after one, two, three or four lines of treatment
* Bendamustine-naive or relapsed after at least one year after the last cycle of a bendamustine-containing regimen
* Previous treatment with BTKi (Bruton Tyrosine Kinase inhibitors) monotherapy or BTKi containing regimens with R/R disease; and/or patients who discontinued BTKi monotherapy or BTKi containing regimens for adverse events and have active disease necessitating treatment.
* Previous treatment with any anti-CD19 agents is allowed (included CAR-T treatment) If previous anti-CD19 treatment has occurred, tissue CD19 expression must be assessed by histology or flow cytometry
* Venetoclax treated patients are allowed.
* Stem cell transplant eligible patients are allowed.
* Measurable nodal or extranodal disease ≥ 1.5 cm in longest diameter, and measurable in 2 perpendicular dimensions. Note: Patients with bone marrow involvement only are eligible. In case of bone marrow infiltration only, bone marrow aspiration and biopsy are mandatory for all staging evaluations
* ECOG (Eastern Cooperative Oncology Group)/WHO (World Health Organization) performance status ≤ 2 (unless MCL-related)
* The following laboratory values at screening (unless due to bone marrow involvement by lymphoma):

  * Absolute Neutrophil count (ANC) \> 1.0×109/L
  * Platelet count ≥ 75.000/mm3
  * Creatinine clearance ≥ 40 mL/min (Cockcroft-Gault formula)
  * Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN (upper limit of normal)
  * Bilirubin ≤ 1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non- hepatic origin)
* Subject understands and voluntarily signs an informed consent form approved by an Independent Ethics Committee (IEC), prior to the initiation of any screening or study-specific procedures.
* Subject must be able to adhere to the study visit schedule and other protocol requirements.
* Life expectancy ≥ 3 months.
* Women of childbearing potential (WOCBP) and men must agree to use effective contraception if sexually active.This applies for the time period between signing of the informed consent form and at least 10 months after last loncastuximab tesirine (ADCT-402) dose. Men with female partners who are of childbearing potential must agree to use effective contraception if sexually active. This applies for the time period between signing of the informed consent form and at least 7 months after last loncastuximab tesirine (ADCT-402) dose.

Exclusion Criteria:

* Subjects who have received a bendamustine containing regimen and relapsed less than one year after the end of treatment.
* Known history of hypersensitivity to human antibodies.
* Allogenic stem cell transplant within 6 months prior to start of first study drug.
* Allogenic stem cell transplant with active / uncontrolled graft-versus-host disease.
* Previous treatment with CD19 targeting agents.
* More than four lines of previous treatment (autologous stem cell transplant performed as part of consolidation to a previous line of therapy should not be considered as a line of therapy).
* Active second malignancy in the last three years other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or any other tumor that the Sponsor and Coordinating Investigator agree and document should not be considered preclusive to participate in the study.
* Major surgery or any anticancer therapy including chemotherapy, immunotherapy, radiotherapy, investigational therapy, including targeted small molecule agents within 14 days prior to start of study drug (R-BAC). A shorter interval in special settings must be approved by the Sponsor and/or Investigator.
* Cardiovascular disease (NYHA, New York Heart Association, class ≥2).
* Significant history of neurologic, psychiatric, endocrinological, metabolic, immunologic, or hepatic disease that would preclude participation in the study or compromise ability to give informed consent.
* Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:

  * Uncontrolled and/or active systemic infection (viral including COVID 19, bacterial or fungal);
  * Chronic or acute hepatitis B (HBV) or hepatitis C (HCV) requiring treatment. Note:

subjects with serologic evidence of prior vaccination to HBV (i.e., HBsAg negative, HBsAb positive and HBcAb negative) or positive HBcAb from previous infection or intravenous immunoglobulins (IVIG) may participate; inactive carriers (HBsAg positive with undetectable HBV DNA) are eligible. Patients with presence of HCV antibody are eligible only if PCR results (polimerase chain reaction) negative for HCV RNA.

* HIV seropositivity.
* Lymphoma with active CNS (central nervous system) involvement at the time of screening, including leptomeningeal disease.
* Congenital long QT syndrome or a corrected QTcF interval of \>480 msec at screening (unless secondary to pacemaker or bundle branch block).
* Any other significant medical illness, abnormality, or condition that would, in the Investigator's judgment, make the patient inappropriate for study participation or put the patient at risk.
* If female, the patient is pregnant or breast-feeding.

Where this trial is running

Brescia, Italy and 20 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Relapsed Mantle Cell LymphomaRefractory Mantle Cell LymphomaRelapsed/Refractory Mantle Cell LymphomaADCT-402BTKi - treatedBTKi intolerant
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.