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

Primary Purpose

Large B-cell Lymphoma

Status

Recruiting

Phase

Phase 2

Locations

Netherlands

Study Type

Interventional

Intervention

89Zr-atezolizumab PET-imaging

About this trial

This is an interventional diagnostic trial for Large B-cell Lymphoma focused on measuring PD-L1, CAR T-cell therapy, Imaging

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

University Medical Center GroningenRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PD-L1 PET-imaging

Arm Description

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.

Outcomes

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.

To correlate the pretreatment 89Zr-atezolizumab uptake to the objective response rate to CAR T-cell therapy.

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.

Secondary Outcome Measures

To correlate the pretreatment 89Zr-atezolizumab distribution to CAR T-cell peak expansion and persistence.

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)).

To correlate tumor 89Zr-atezolizumab uptake with tumor and immune cell PD-L1 expression as assessed by immunohistochemistry on a fresh contemporaneous tumor biopsy.

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.

To determine the incidence of a treatment-related inflammatory signal on 18F-FDGPET/CT scan (histiocytic/sarcoid-like reaction) after CAR T-cell therapy.

Full Information

NCT ID

NCT05404048

First Posted

May 5, 2022

Last Updated

July 15, 2022

Sponsor

University Medical Center Groningen

1. Study Identification

Unique Protocol Identification Number

NCT05404048

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Recruiting

Study Start Date

May 18, 2022 (Actual)

Primary Completion Date

May 2024 (Anticipated)

Study Completion Date

May 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Medical Center Groningen

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Large B-cell Lymphoma

Keywords

PD-L1, CAR T-cell therapy, Imaging

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

PD-L1 PET-imaging

Arm Type

Experimental

Arm Description

Intervention Type

Other

Intervention Name(s)

89Zr-atezolizumab PET-imaging

Intervention Description

89Zr-atezolizumab tracer injection + PET/CT-scan

Primary Outcome Measure Information:

Title

To evaluate the expression of PD-L1 in normal tissue and lymphoma lesions before CAR T-cell therapy by 89Zr-atezolizumab PET/CT imaging.

Time Frame

2 year

Title

To correlate the pretreatment 89Zr-atezolizumab uptake to the objective response rate to CAR T-cell therapy.

Time Frame

2 year

Title

Time Frame

2 year

Secondary Outcome Measure Information:

Title

To correlate the pretreatment 89Zr-atezolizumab distribution to CAR T-cell peak expansion and persistence.

Time Frame

2 year

Title

Time Frame

2 year

Title

To correlate tumor 89Zr-atezolizumab uptake with tumor and immune cell PD-L1 expression as assessed by immunohistochemistry on a fresh contemporaneous tumor biopsy.

Time Frame

2 year

Title

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.

Time Frame

2 year

Title

To determine the incidence of a treatment-related inflammatory signal on 18F-FDGPET/CT scan (histiocytic/sarcoid-like reaction) after CAR T-cell therapy.

Time Frame

2 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Janneke W de Boer, MD

Phone

+31625573522

j.w.de.boer@umcg.nl

First Name & Middle Initial & Last Name or Official Title & Degree

Tom van Meerten, MD,PhD

Phone

+31 50 3612770

t.van.meerten@umcg.nl

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Tom van Meerten, MD,PhD

Organizational Affiliation

UMCG

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Medical Center Groningen

City

Groningen

ZIP/Postal Code

9713GZ

Country

Netherlands

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Janneke W de Boer, MD

j.w.de.boer@umcg.nl

First Name & Middle Initial & Last Name & Degree

Tom van Meerten, MD,PhD

t.van.meerten@umcg.nl

12. IPD Sharing Statement

Plan to Share IPD

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

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