CD30 Imaging in Diffuse Large B-cell Lymphoma

Diffuse Large B-cell-lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06186986
• Other study ID #: NL202100762
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: January 2024
• Est. completion date: January 2026

Study information

• Verified date: December 2023
• Source: University Medical Center Groningen
• Contact: Marijn de Vries
• Phone: 0610013023
• Email: m.l.de.vries[@]umcg.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: January 2026
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Diffuse Large B-cell-lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Brentuximab vedotin
5 Participants will receive unlabeled brentuximab and 20 participants will receive 89ZR-Brentuximab.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University Medical Center Groningen	Takeda

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	An optimized 89Zr-brentuximab imaging protocol for visualisation of CD30 distribution by PET-scan	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
Primary	Safety profile of the 89Zr-brentuximab tracer	AE related to imaging protocol with the 89Zr-brentuximab tracer	2 years
Primary	Relation 89Zr-brentuximab biodistribution and CD30 expression	Relation between 89Zr-brentuximab tracer uptake and CD30 protein expression	2 years
Secondary	Relation between 89Zr-brentuximab uptake and response to therapy	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