CD30 Imaging in Diffuse Large B-cell Lymphoma

December 15, 2023 updated by: Marcel Nijland, University Medical Center Groningen

Molecular Imaging of Zirconium-89-labeled Brentuximab as a Tool to Investigate Brentuximab Biodistribution in CD30-positive Lymphoma

The antibody drug conjugate (ADC) brentuximab vedotin (BV), targeting CD30, is currently registered for the treatment of previously untreated stage III-IV Hodgkin lymphoma (HL), relapsed Hodgkin lymphoma, relapsed systemic anaplastic large T-cell lymphoma (sALCL) and relapsed CD30 expressing cutaneous T-cell lymphoma, type mycosis fungoides (CTCL, MF) with overall response rates (ORR) up to 70%. BV has shown promising results in other CD30 expressing non-hodgkin lymphoma (NHL), including relapsed angio-immunoblastic T-cell lymphoma (AITL), peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), post-transplant lymphoproliferative diseases (PTLD) and diffuse large B-cell lymphoma (DLBCL) with ORR rates of 50%, 40% and 45%, respectively. Despite expression of CD30 on tumor cells, no objective responses were observed in relapsed primary mediastinal B-cell lymphoma (PMBCL). Strikingly, thus far correlative studies have not found predictive markers in tissue or blood that are predictive for response to treatment. Since CD30 expression in tumor tissue is unrelated to treatment outcome, this suggests involvement of phenomena like tumor heterogeneity, drug uptake in the tumor micro-environment or very low CD30 expression below the immunohistochemistry (IHC) threshold. In this imaging study the biodistribution of brentuximab will be investigated by using Zirconium-89 (89Zr)-labeled brentuximab. 89Zr-brentuximab imaging will help to assess tumor uptake and pharmacokinetic (PK) and -dynamic properties of brentuximab in patients who are intended to be treated with BV, either in one of the registered indications (HL, CTCL and sALCL) or as part of the HOVON 136 trial for patients with DLBCL. The hypothesize is that the results of this imaging study might be used to facilitate the identification of patients that would benefit most from BV treatment

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • All patients with histologically proven CD30-positive (i.e. > 1% cells) lymphomas who will be treated with BV, including:

    • HL
    • T-NHL
    • CTCL

    • DLBCL

      • Age ≥18 years
      • Signed written informed consent form (approved by the Institutional Review Board [IRB]/ Independent Ethics Committee [IEC]) obtained prior to any study specific screening procedures
      • Measurable disease: on CT scan at least 1 lesion/node with a long axis of > 1.5 cm and at least one positive lesion on 18F-FDG PET scan
      • World Health Organization (WHO) performance status 0-2 (see appendix A)
      • Adequate hepatic function: total bilirubin ≤ 1.5 times upper limit of normal (ULN) (unless due to lymphoma involvement of the liver or a known history of Gilbert's syndrome as defined by > 80% unconjugated bilirubin) and Alanine Aminotransferase (ALAT) / Aspartate Aminotransferase (ASAT) ≤ 3 times ULN (unless due to lymphoma involvement of the liver; in that case ALAT/ASAT may be elevated up to 5 times ULN)
      • Adequate renal function: GFR > 50 milliliter/ minute (ml/min) as estimated by the cockcroft & gault formula at rehydration:

Creatinine Clearance (CrCL) = (140-age [in years] x weight [kg] (x 0.85 for females) (0.815 x serum creatinine [μmol/L])

  • Adequate bone marrow function: Absolute neutrophil count (ANC) ≥ 1.5 x 109/liter (L) and platelet count ≥100 x 109/L, unless caused by diffuse bone marrow infiltration by lymphoma
  • Hemoglobin must be ≥ 8 g/dL (5.0 mmol/L), transfusion is allowed
  • Life expectancy of >3 months with treatment
  • Negative pregnancy test at study entry, if applicable

Exclusion Criteria:

  • Prior allergic reaction or known hypersensitivity to immunoglobulins, recombinant proteins, murine proteins, or to any excipient contained in the dug formulation of BV.

    • Peripheral sensory or motor neuropathy grade ≥ 2
    • Patients with a serious psychiatric disorder that could, in the investigator's opinion, potentially interfere with the completion of treatment according to protocol
    • Patients who have any severe and/or uncontrolled medical condition or other conditions that could affect their participation in the study
    • Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
    • Claustrophobia to the extent that PET-CT is impossible
    • Pregnant or lactating women. Documentation of a negative pregnancy test must be available for pre-menopausal women with intact reproductive organs and for women less than two years after menopause

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part 1
In Part 1 of this side study a minimum of 5 eligible patients will undergo 89Zr-brentuximab-PET scans at 3 different time points (1, 4 and 7 days after tracer injection) either without (2 patients) or with preceding administration of 10 mg (3 patients) or more (n patients) of unlabeled brentuximab.
Drug: Brentuximab vedotin
5 Participants will receive unlabeled brentuximab and 20 participants will receive 89ZR-Brentuximab.
Other Names:
  • 89ZR-Brentuximab
Experimental: Part 2
In Part 2 of this side study the optimized imaging schedule from Part 1 will be used to investigate biodistribution and tumor uptake of 89Zr-brentuximab in 15 patients and correlate imaging data to baseline sCD30 serum levels, CD30 IHC and CD30 Gene Expression Profiling (GEP).
Drug: Brentuximab vedotin
5 Participants will receive unlabeled brentuximab and 20 participants will receive 89ZR-Brentuximab.
Other Names:
  • 89ZR-Brentuximab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
An optimized 89Zr-brentuximab imaging protocol for visualisation of CD30 distribution by PET-scan
Time Frame: 2 years
89Zr-brentuximab imaging protocol, including the dose of brentuximab (mg), the dose of 89Zr-brentuximab (mg) and the time (day) of PET-scanning after 89Zr-brentuximab administration
2 years
Safety profile of the 89Zr-brentuximab tracer
Time Frame: 2 years
AE related to imaging protocol with the 89Zr-brentuximab tracer
2 years
Relation 89Zr-brentuximab biodistribution and CD30 expression
Time Frame: 2 years
Relation between 89Zr-brentuximab tracer uptake and CD30 protein expression
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relation between 89Zr-brentuximab uptake and response to therapy
Time Frame: 2 years
The extent of heterogeneity in 89Zr-brentuximab uptake and the potential correlation with response to therapy (as determined via 18F-FDG PET/CT scan per the International Working Group criteria (1,2).
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Medical Center Groningen

Collaborators

Takeda

Investigators

  • Principal Investigator: Marcel Nijland, MD, UMCGoningen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 1, 2024

Primary Completion (Estimated)

January 1, 2025

Study Completion (Estimated)

January 1, 2026

Study Registration Dates

First Submitted

October 5, 2023

First Submitted That Met QC Criteria

December 15, 2023

First Posted (Estimated)

January 1, 2024

Study Record Updates

Last Update Posted (Estimated)

January 1, 2024

Last Update Submitted That Met QC Criteria

December 15, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL202100762

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

all IPD that underlie results in a publication

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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