Molecular Imaging Using Radiolabeled Atezolizumab to Assess Atezolizumab Biodistribution in Lymphoma Patients

NCT03850028 | Withdrawn

• 3 other identifiers: 2017005992017-003511-20NL63047.042.18
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

Molecular imaging can be used for the noninvasive assessment of biodistribution of monoclonal antibodies. Atezolizumab has previously successfully been labeled with the radionucleotide Zirconium-89 (89Zr) and studied in solid malignancies (NCT02453984). The results of atezolizumab biodistribution can help to get a better understanding of the response mechanisms, the relation with minimal residual disease, the relation with the status of the T-cell and natural killer (NK)-cell repertoire and toxicity of programmed death ligand 1 (PDL1) checkpoint inhibition. Possibly in the future this will facilitate optimal patient selection. Sequential 89Zr-atezolizumab positron emission tomography (PET) scans can provide information on the dynamics of atezolizumab biodistribution over time. In combination with repeated characterization of tumor tissue and blood samples, these results can give inside in primary and acquired resistance. In this parallel study of the HOVON 151 trial, 89Zr-atezolizumab-PET-scans will be used to evaluate 20 high risk DLBCL patients before and after induction (R-CHOP) therapy, and at suspected relapse during or after atezolizumab consolidation (HOVON 151).

Conditions

Diffuse Large B-Cell Lymphoma, Not Otherwise Specified

Keywords

high risk DLBCL; molecular imaging; 89Zr-atezolizumab-PET; PDL1 imaging

Outcome Measures

Primary Outcomes (1)

• Biodistribution of 89Zr-atezolizumab

  The biodistribution of the tracer 89Zr-atezolizumab as assessed with 89Zr-atezolizumab PET scans.

  From 2 weeks before R-CHOP until 52 weeks after R-CHOP

Secondary Outcomes (4)

• PDL1 and human leukocyte antigen (HLA) expression using immunohistochemistry (IHC)

  IHC for PDL1 and HLA expression on archival tumor tissue will be performed after initial biopsy at time of diagnosis.

• Soluble programmed death ligand 1 (sPDL1) measurement using an enzyme-linked immunosorbent assay (ELISA).

  From 2 weeks before R-CHOP until 52 weeks after R-CHOP

• Gene expression profiling (GEP) via Nanostring

  From 2 weeks before R-CHOP until 52 weeks after R-CHOP

• Next generation sequencing (NGS) data

  From 2 weeks before R-CHOP until 52 weeks after R-CHOP

Other Outcomes (2)

• T- and NK-cell dynamics in response to R-CHOP therapy

  From 2 weeks before R-CHOP until 52 weeks after R-CHOP

• Gut microbiome dynamics in response to R-CHOP therapy

  From 2 weeks before R-CHOP until 52 weeks after R-CHOP

Study Arms (1)

Imaging cohort

OTHER

All study participants will be allocated to this arm (single-arm study). Study participants will undergo a maximum of 3 89Zr-atezolizumab PET scans.

Other: 89Zr-atezolizumab PET scans

Interventions

89Zr-atezolizumab PET scans OTHER

The anti-PDL1 antibody atezolizumab, labeled with Zirconium-89 (89Zr) will be used as a molecular imaging tracer for PET scanning. These 89Zr-atezolizumab PET scans will be performed before and after induction therapy (R-CHOP) and at suspected relapse during or after consolidation treatment with atezolizumab (treatment trial HOVON 151).

Imaging cohort

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 (inclusive) years
• Patients with a confirmed histologic diagnosis of diffuse large B-cell lymphoma not otherwise specified (DLBCL-NOS) based upon a representative histology specimen according to the World Health Organization (WHO) classification, revision 2016 (see appendix A)
• Ann Arbor stages II-IV (see appendix B)
• WHO performance status 0 - 1 (see appendix E)
• international prognostic index (IPI) ≥ 3 at diagnosis (see appendix C)
• Negative pregnancy test at study entry
• Patient is willing and able use adequate contraception during and until 5 months after the last protocol treatment.
• Written informed consent
• Patient is capable of giving a written informed consent

You may not qualify if:

• Diagnosis
• All histopathological diagnoses other than DLBCL-NOS according to the WHO classification, revision 2016 (see appendix A), including:
• High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 translocations
• Testicular large B-cell lymphoma
• Primary mediastinal B cell lymphoma
• Transformed indolent lymphoma
• Post-transplant lymphoproliferative disorder
• Organ dysfunction
• Clinical signs of severe pulmonary dysfunction
• Clinical signs of heart failure (NYHA classification II-IV)
• Symptomatic coronary artery disease or cardiac arrhythmias not well controlled with medication.
• Myocardial infarction during the last 6 months
• Significant renal dysfunction (serum creatinine ≥ 150 umol/l or clearance ≤ 30ml/min
• Creatinine clearance (CrCl) may be calculated by Cockcroft -Gault formula:
• CrCl = (140 - age \[in years\]) x weight \[kg\] (x 0.85 for females) / (0.815 x serum creatinine \[μmol/L\])

Sponsors & Collaborators

• University Medical Center Groningen: lead
• Amsterdam UMC, location VUmc: collaborator
• Stichting Hemato-Oncologie voor Volwassenen Nederland: collaborator
• Hoffmann-La Roche: collaborator

Study Sites (2)

VU University Medical Center

Amsterdam, North Holland, 1081HV, Netherlands

Location

University Medical Center Groningen

Groningen, 9100 RB, Netherlands

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Marcel Nijland, MD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: hematologist and priniciple investigator

Study Record Dates

• First Submitted: February 15, 2019
• First Posted: February 21, 2019
• Study Start: May 22, 2019
• Primary Completion: May 1, 2022
• Study Completion: May 1, 2022
• Last Updated: May 15, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

NL (2)