PD-L1 PET-imaging During CAR T-cell Therapy

Sponsor

University Medical Center Groningen (Other)

Overall Status

Recruiting

CT.gov ID

NCT05404048

Collaborator

(none)

Enrollment

Location

Arm

35.4

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Large B-cell Lymphoma	Other: 89Zr-atezolizumab PET-imaging	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

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

Actual Study Start Date :

May 18, 2022

Anticipated Primary Completion Date :

May 1, 2024

Anticipated Study Completion Date :

May 1, 2025

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.