- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05453396
Loncastuximab Tesirine for the Treatment of Relapsed or Refractory B-Cell Malignancies
April 17, 2024 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
- Recurrent Mantle Cell Lymphoma
- Refractory B-Cell Non-Hodgkin Lymphoma
- Recurrent B-Cell Non-Hodgkin Lymphoma
- Recurrent Diffuse Large B-Cell Lymphoma
- Refractory Diffuse Large B-Cell Lymphoma
- Post-Transplant Lymphoproliferative Disorder
- Refractory Mantle Cell Lymphoma
- Recurrent Follicular Lymphoma
- Refractory Follicular Lymphoma
- Recurrent Neoplastic Post-Transplant Lymphoproliferative Disorder
- Refractory Neoplastic Post-Transplant Lymphoproliferative Disorder
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.
After completion of study treatment, patients are followed up for 5 years.
Study Type
Interventional
Enrollment (Estimated)
40
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
- Name: Stephen D. Smith
- Phone Number: 206-606-6546
- Email: ssmith50@fredhutch.org
Study Locations
-
-
Washington
-
Seattle, Washington, United States, 98109
- Recruiting
- Fred Hutch/University of Washington Cancer Consortium
-
Principal Investigator:
- Stephen D. Smith
-
Contact:
- Stephen D. Smith
- Phone Number: 206-606-6546
- Email: ssmith50@fredhutch.org
-
-
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 1: CD19+ relapsed/refractory post-transplant lymphoproliferative disorder (PTLD),
- 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)
- Group 4: Relapsed/refractory, CD19-negative B-NHL by both immunohistochemistry and flow cytometry (minimal to absent expression). Patients (Pts) must have had at least 1 prior therapy, and no alternative with a more favorable benefit/risk ratio in the judgment of the treating investigator
- 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.
|
Given IV
Other Names:
|
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
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, 2025
Study Completion (Estimated)
July 6, 2026
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)
April 19, 2024
Last Update Submitted That Met QC Criteria
April 17, 2024
Last Verified
April 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphatic Diseases
- Immunoproliferative Disorders
- Disease Attributes
- Lymphoma
- Lymphoma, Follicular
- Lymphoma, B-Cell
- Lymphoma, Large B-Cell, Diffuse
- Recurrence
- Lymphoma, Non-Hodgkin
- Lymphoma, Mantle-Cell
- Lymphoproliferative Disorders
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Loncastuximab tesirine
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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