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| Name | Class |
|---|---|
| Takeda | INDUSTRY |
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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1 | Experimental | 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. |
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| Part 2 | Experimental | 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). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Brentuximab vedotin | Drug | 5 Participants will receive unlabeled brentuximab and 20 participants will receive 89ZR-Brentuximab. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Safety profile of the 89Zr-brentuximab tracer | AE related to imaging protocol with the 89Zr-brentuximab tracer | 2 years |
| Relation 89Zr-brentuximab biodistribution and CD30 expression | Relation between 89Zr-brentuximab tracer uptake and CD30 protein expression | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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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
Creatinine Clearance (CrCL) = (140-age [in years] x weight [kg] (x 0.85 for females) (0.815 x serum creatinine [μmol/L])
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.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Marijn de Vries | Contact | 0610013023 | m.l.de.vries@umcg.nl | |
| Imke Kraai-Nomden | Contact | 050-3613385 | i.h.kraai@umcg.nl |
| Name | Affiliation | Role |
|---|---|---|
| Marcel Nijland, MD | UMCGoningen | Principal Investigator |
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all IPD that underlie results in a publication
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| ID | Term |
|---|---|
| D054739 | Dendritic Cell Sarcoma, Interdigitating |
| ID | Term |
|---|---|
| D015620 | Histiocytic Disorders, Malignant |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D015614 | Histiocytosis |
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| ID | Term |
|---|---|
| D000079963 | Brentuximab Vedotin |
| ID | Term |
|---|---|
| D009842 | Oligopeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D061067 | Antibodies, Monoclonal, Humanized |
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| D008206 |
| Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |