Evaluating PD-L1 expression in Large B-cell Lymphoma during CAR T-cell therapy

Programmed Death Ligand 1 (PD-L1)-PET Imaging in Patients With (Diffuse) Large B-cell Lymphoma Who Are Treated With CD19-directed CAR T-cell Therapy: a Pilot Study

This study is trying to see if measuring a specific protein in patients with Large B-cell lymphoma can help understand why some people don’t respond to CAR T-cell therapy.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Medical Center Groningen (other)
• Drugs / interventions: atezolizumab, blinatumomab, CAR T, chimeric antigen receptor
• Locations: 1 site (Groningen)
• Trial ID: NCT05404048 on ClinicalTrials.gov

What this trial studies

This pilot trial aims to assess the expression of PD-L1 in patients with Large B-cell lymphoma (LBCL) and its potential link to non-responsiveness to CAR T-cell therapy. The study utilizes 89Zr-atezolizumab PET/CT imaging to non-invasively distinguish between active lymphoma and treatment-related inflammatory responses in patients showing positive FDG PET/CT signals at the end of treatment. It is a single-center, single-arm Phase 2 trial focusing on improving patient outcomes through better imaging techniques.

Who should consider this trial

Good fit: Ideal candidates include adults over 18 with histologically confirmed LBCL and measurable disease who can safely undergo biopsy.

Not a fit: Patients with significant comorbidities or those unable to comply with the study protocol may not benefit from this trial.

Why it matters

Potential benefit: If successful, this study could enhance the understanding of treatment responses in LBCL patients and improve the management of CAR T-cell therapy.

How similar studies have performed: While the use of imaging in CAR T-cell therapy is being explored, this specific approach using PD-L1 PET imaging is relatively novel.

Eligibility criteria

Inclusion Criteria:

* Histologically confirmed LBCL and associated subtypes, defined by WHO 2016 classification
* Tumor lesion(s) of which a histological biopsy can safely be obtained according to Standard clinical care procedures.
* Measurable disease, as defined by Lugano criteria.
* If has history of central nervous system (CNS) disease, then must have no signs or symptoms of CNS disease, no active disease on magnetic resonance imaging (MRI) and absence of large cell lymphoma in cerebral spinal fluid (CSF) on cytospin preparation and flow cytometry, regardless of the number of white blood cells.
* If has history of cerebral vascular accident (CVA), the CVA event must be 12 months prior to apheresis and any neurological deficits must be stable.
* Signed informed consent.
* Age \>18 at the time of signing informed consent.
* Life expectancy \>12 weeks.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Ability to comply with the protocol.

Exclusion Criteria:

* Signs or symptoms of active infection within 2 weeks prior to 89Zr-atezolizumab injection, unless treated to resolution.
* Prior CD19-directed CAR T-cell therapy or other bi-specific antibodies targeting CD19 receptor (e.g.blinatumomab).
* History of severe allergy, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
* Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of 89Zr-atezolizumab, or that may affect the interpretation of the results or render the patient at high risk for complications.

Where this trial is running

Groningen

• University Medical Center Groningen — Groningen, Netherlands (RECRUITING)

Study contacts

• Principal investigator: Tom van Meerten, MD,PhD — UMCG
• Study coordinator: Janneke W de Boer, MD

Conditions: Large B-cell Lymphoma, PD-L1, CAR T-cell therapy, Imaging