PD-L1 PET-imaging 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 is a single-center, single-arm pilot trial designed to evaluate the expression of PD-L1 in patients with Large B-cell lymphoma (LBCL) and its role in non-responsiveness to chimeric antigen receptor (CAR) T-cell therapy in a non-invasive manner. Moreover, within this trial 89Zr-atezolizumab PET/CT imaging as a tool to distinguish lymphoma activity from a treatment-related inflammatory signal (histiocytic/sarcoid-like reaction) in patients with an end-of-treatment positive FDG PET/CT signal will be evaluated.

Study Overview

• Status: Recruiting
• Conditions: Large B-cell Lymphoma
• Intervention / Treatment: Other: 89Zr-atezolizumab PET-imaging

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Janneke W de Boer, MD; Phone Number: +31625573522; Email: j.w.de.boer@umcg.nl
• Study Contact Backup: Name: Tom van Meerten, MD,PhD; Phone Number: +31 50 3612770; Email: t.van.meerten@umcg.nl

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713GZ
    • Recruiting
    • University Medical Center Groningen
    • Contact: Janneke W de Boer, MD; Email: j.w.de.boer@umcg.nl
    • Contact: Tom van Meerten, MD,PhD; Email: t.van.meerten@umcg.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PD-L1 PET-imaging; The main intervention of this study is 89Zr-atezolizumab PET-scan combined with a low-dose CT-scan. The PET/CT scan will be performed before infusion of CAR T-cell therapy. In patients with an end-of-treatment F-FDG positive PET-signal a second 89Zr-atezolizumab PET/CT-scan will be performed.	Other: 89Zr-atezolizumab PET-imaging; 89Zr-atezolizumab tracer injection + PET/CT-scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate the expression of PD-L1 in normal tissue and lymphoma lesions before CAR T-cell therapy by 89Zr-atezolizumab PET/CT imaging.	2 year
To correlate the pretreatment 89Zr-atezolizumab uptake to the objective response rate to CAR T-cell therapy.	2 year
To evaluate the utility of the 89Zr-atezolizumab uptake to distinguish lymphoma activity from a treatment-related inflammatory reaction in patients with an end-of-treatment 18F-FDG-positive PET/CT signal.	2 year

Secondary Outcome Measures

Outcome Measure	Time Frame
To correlate the pretreatment 89Zr-atezolizumab distribution to CAR T-cell peak expansion and persistence.	2 year
To correlate the pretreatment 89Zr-atezolizumab uptake to CAR T-cell therapy related grade 1-5 adverse events (cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS)).	2 year
To correlate tumor 89Zr-atezolizumab uptake with tumor and immune cell PD-L1 expression as assessed by immunohistochemistry on a fresh contemporaneous tumor biopsy.	2 year
To compare the 89Zr-atezolizumab distribution in irradiated versus non-irradiated lymphoma lesions in patients who require radiotherapy as a bridging strategy prior to CAR T-cell infusion.	2 year
To determine the incidence of a treatment-related inflammatory signal on 18F-FDGPET/CT scan (histiocytic/sarcoid-like reaction) after CAR T-cell therapy.	2 year

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Investigators: Principal Investigator: Tom van Meerten, MD,PhD, UMCG

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2022
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: May 5, 2022
• First Submitted That Met QC Criteria: May 31, 2022
• First Posted (Actual): June 3, 2022

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Imaging; PD-L1; CAR T-cell therapy
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Atezolizumab
• Other Study ID Numbers: 202100663

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: No
• Studies a U.S. FDA-regulated device product: No