Loncastuximab Tesirine for the Treatment of Relapsed or Refractory B-Cell Malignancies

May 7, 2026 updated by: University of Washington

A Pilot Study of Loncastuximab Tesirine in Specific Populations of Relapsed/Refractory B-Cell Malignancies

This phase II trial tests whether loncastuximab tesirine works to shrink tumors in patients with B-cell malignancies that have come back (relapsed) or does not respond to treatment (refractory). Loncastuximab tesirine is a monoclonal antibody, called loncastuximab, linked to a chemotherapy drug, called tesirine. Loncastuximab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD19 receptors, and delivers tesirine to kill them.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

OUTLINE:

Patients receive loncastuximab tesirine intravenously (IV) over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone marrow biopsy and aspiration throughout the study.

After completion of study treatment, patients are followed up for 5 years.

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Fred Hutch/University of Washington Cancer Consortium
        • Principal Investigator:
          • Stephen D. Smith
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Male or female patient aged 18 years or older

  • Disease-specific criteria:

    • Group 2: Relapsed/refractory. CD19+ B-cell non-Hodgkin lymphoma (B-NHL) excluding Waldenstrom's macroglobulinemia and marginal zone lymphoma, (at least 1 prior therapy, and no alternative with a more favorable benefit/risk ratio in the judgment of the treating investigator.
    • Group 3: CD19+ diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), or mantle cell lymphoma (MCL) relapsing after chimeric antigen receptor (CAR) T-cell therapy or allogeneic transplant (at least 30 days from CAR T/transplant)
  • Have measurable nodal or extranodal disease, including at least 1 disease site measuring 1.5 cm in longest dimension; or splenomegaly; or histologic marrow involvement for marrow-only presentations
  • Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) performance scale (PS)
  • Absolute neutrophil count (ANC) >= 1.0 x 10^3/uL (off growth factors at least 72 hours), unless due to marrow involvement by lymphoma in which case ANC must be >= 0.5 x 10^3/uL
  • Platelet count >= 75 x 10^3/uL without transfusion in the prior 7 days, unless due to disease including splenomegaly in which case platelet count must be >= 50 x 10^3/uL
  • Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) =< 3 x the upper limit of normal (ULN)
  • Total bilirubin =< 1.5 x ULN (patients with known Gilbert's syndrome may have a total bilirubin up to =< 3 x ULN)
  • Blood creatinine =< 2.0 x ULN or calculated creatinine clearance >= 50 mL/min by the Cockcroft and Gault equation
  • Negative beta-human chorionic gonadotropin (beta-HCG) pregnancy test within 7 days prior to start of study drug (cycle 1 day 1 [C1D1]) for women of childbearing potential
  • Women of childbearing potential must agree to use a highly effective method of contraception from the time of giving informed consent until at least 10 months after the last dose of loncastuximab tesirine
  • Men with female partners who are of childbearing potential must agree that they will use a condom from the time of giving informed consent until at least 7 months after the patient receives his last dose of loncastuximab tesirine

Exclusion Criteria:

  • Previous treatment with loncastuximab tesirine
  • Known history of hypersensitivity to loncastuximab tesirine
  • Active second primary malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy
  • Uncontrolled graft-versus-host disease
  • Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive or hepatitis B virus [HBV] deoxyribonucleic acid [DNA] detectable) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
  • Is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 9 months after the last dose of trial treatment
  • Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath)
  • Lymphoma with active central nervous system (CNS) involvement at the time of screening, including active leptomeningeal disease. A history of treated CNS disease permitted
  • Significant medical comorbidities, including but not limited to unstable angina, congestive heart failure (New York Heart Association class III or greater), uncontrolled atrial or ventricular cardiac arrhythmia, that would, in the Investigator's judgment, make the patient inappropriate for study participation or put the patient at risk
  • Major surgery, radiotherapy, chemotherapy or other anti-neoplastic therapy within 14 days prior to start of study drug (C1D1)
  • Use of any other experimental medication within 14 days prior to start of study drug (C1D1)
  • Planned live vaccine administration after starting study drug (C1D1)
  • 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
  • Is currently participating in a study and receiving an investigational agent or is using an investigational device within 4 weeks of the first dose of treatment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (loncastuximab tesirine)
Patients receive loncastuximab tesirine IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo bone marrow biopsy and aspiration throughout the study.
Biological: Loncastuximab Tesirine
Given IV
Other Names:
  • Zynlonta
  • ADCT-402
  • ADC ADCT-402
  • Anti-CD19 PBD-conjugate ADCT-402
  • Loncastuximab Tesirine-lpyl
  • MT 2111
  • MT-2111
  • MT2111
Procedure: Bone Marrow Biopsy
Undergo bone marrow biopsy and aspiration
Procedure: Bone Marrow Aspiration
Undergo bone marrow biopsy and aspiration

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response rate (ORR)
Time Frame: Up to 5 years
According to the 2014 Lugano classification Cheson 20146 as determined by local review; ORR is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR).
Up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rates of grade 3-5 adverse event
Time Frame: Up until 30 days after the last dose of the last study drug
Up until 30 days after the last dose of the last study drug
Rate of discontinuation due to adverse events
Time Frame: Up until 30 days after the last dose of the last study drug
Up until 30 days after the last dose of the last study drug
Clinical benefit rate
Time Frame: Up to 5 years
Defined as stable disease + partial or complete response.
Up to 5 years
Duration or response
Time Frame: Time from the first documentation of tumor response to disease progression or death, assessed up to 5 years
Time from the first documentation of tumor response to disease progression or death, assessed up to 5 years
Progression free survival
Time Frame: Time between start of treatment and the first documentation of recurrence, progression, or death, assessed up to 5 years
Time between start of treatment and the first documentation of recurrence, progression, or death, assessed up to 5 years
Overall survival
Time Frame: Time between the start of treatment and death from any cause, assessed up to 5 years
Time between the start of treatment and death from any cause, assessed up to 5 years
Incidence of grade 3-5 drug-related toxicity
Time Frame: Up until 30 days after the last dose of the last study drug
Up until 30 days after the last dose of the last study drug

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Washington

Investigators

  • Principal Investigator: Stephen D. Smith, Fred Hutch/University of Washington Cancer Consortium

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 7, 2023

Primary Completion (Estimated)

December 15, 2027

Study Completion (Estimated)

July 6, 2028

Study Registration Dates

First Submitted

July 6, 2022

First Submitted That Met QC Criteria

July 6, 2022

First Posted (Actual)

July 12, 2022

Study Record Updates

Last Update Posted (Actual)

May 11, 2026

Last Update Submitted That Met QC Criteria

May 7, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RG1122400
  • NCI-2022-05221 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • 10980 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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