Treatment for relapsed or refractory B-cell cancers using loncastuximab tesirine

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

This study is testing a new treatment called loncastuximab tesirine to see if it can help shrink tumors in people with relapsed or refractory B-cell cancers.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Washington (Academic / other)
• Drugs / interventions: loncastuximab, CAR T, chimeric antigen receptor, chemotherapy
• Locations: 1 site (Seattle, Washington)
• Trial ID: NCT05453396 on ClinicalTrials.gov

What this trial studies

This phase II trial evaluates the effectiveness of loncastuximab tesirine in shrinking tumors in patients with relapsed or refractory B-cell malignancies. The treatment involves administering loncastuximab tesirine intravenously over 30 minutes on the first day of each 21-day cycle for a total of six cycles, unless disease progression or unacceptable toxicity occurs. Loncastuximab is a targeted therapy that binds to CD19 receptors on cancer cells, delivering the chemotherapy drug tesirine directly to kill the cancer cells. Patients will be monitored for five years after treatment completion to assess long-term outcomes.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with specific types of relapsed or refractory B-cell malignancies, particularly those expressing CD19.

Not a fit: Patients with B-cell malignancies that do not express CD19 or those who have not received prior therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new option for patients with difficult-to-treat B-cell malignancies.

How similar studies have performed: Other studies have shown promise with targeted therapies for B-cell malignancies, suggesting potential success for this approach.

Eligibility criteria

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

Where this trial is running

Seattle, Washington

• Fred Hutch/University of Washington Cancer Consortium — Seattle, Washington, United States (Recruiting)

Study contacts

• Principal investigator: Stephen D. Smith — Fred Hutch/University of Washington Cancer Consortium
• Study coordinator: Stephen D. Smith

Conditions Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Mantle Cell Lymphoma