Diffuse Large B-cell-lymphomaPhase 3NCT06186986
CD30 Imaging in Diffuse Large B-cell Lymphoma
A Phase 3 study testing Brentuximab vedotin in people with Diffuse Large B-cell-lymphoma, run by University Medical Center Groningen.
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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Diffuse Large B-cell-lymphoma
- What is being tested?
- Brentuximab vedotin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- No sites listed yet
- Study dates
- Jan 2024to Jan 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Trial locations and contacts
No sites are listed yet.
About this study
Official title: 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
- Conditions
- Diffuse Large B-cell-lymphoma
- Being tested
- Brentuximab vedotin
- Medical subject headings
- Dendritic Cell Sarcoma, Interdigitating
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Brentuximab vedotinDrug
Also called 89ZR-Brentuximab
5 Participants will receive unlabeled brentuximab and 20 participants will receive 89ZR-Brentuximab.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Brentuximab vedotin |
| 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). Receives: Drug: Brentuximab vedotin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 2 years
Safety profile of the 89Zr-brentuximab tracer
AE related to imaging protocol with the 89Zr-brentuximab tracer
Measured: 2 years
Relation 89Zr-brentuximab biodistribution and CD30 expression
Relation between 89Zr-brentuximab tracer uptake and CD30 protein expression
Measured: 2 years
Secondary outcomes (1)
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).
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jan 2024
- Study startJan 2024 (estimated)
- Primary completionJan 2025 (estimated)
- Study completionJan 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Large B-cell-lymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Collaborators
- Takeda
- Responsible party
- Principal investigator, Marcel Nijland, University Medical Center Groningen
- Investigators
- Marcel Nijland, MD, Principal investigator, UMCGoningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06186986
- Sponsor's protocol ID
- NL202100762
- Status last verified
- Dec 2023
- First submitted
- 5 Oct 2023
- Last updated
- 2 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: all IPD that underlie results in a publication
Study at a glance
From the registry record, last updated by the sponsor on 2 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Molecular Imaging of Zirconium-89-labeled Brentuximab as a Tool to Investigate Brentuximab Biodistribution in CD30-positive Lymphoma
- ClinicalTrials.gov ID
- NCT06186986
- Acronym / sponsor ID
- NL202100762
- Conditions
- Diffuse Large B-cell-lymphoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Collaborators
- Takeda
- Study start
- Jan 2024 (estimated)
- Primary completion
- Jan 2025 (estimated)
- Study completion
- Jan 2026 (estimated)
- First posted
- 2 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part 1 | Experimental | Drug: Brentuximab vedotinIn 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. |
| Part 2 | Experimental | Drug: Brentuximab vedotinIn 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). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- All patients with histologically proven CD30-positive (i.e. > 1% cells) lymphomas who will be treated with BV, including:
- 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
Key exclusion criteria (7 listed)
- Prior allergic reaction or known hypersensitivity to immunoglobulins, recombinant proteins, murine proteins, or to any excipient contained in the dug formulation of BV.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Brentuximab vedotinAlso: 89ZR-Brentuximab5 Participants will receive unlabeled brentuximab and 20 participants will receive 89ZR-Brentuximab. | Drug | Part 1, Part 2 |
Primary outcome
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
Safety profile of the 89Zr-brentuximab tracer
Time frame: 2 years
AE related to imaging protocol with the 89Zr-brentuximab tracer
Relation 89Zr-brentuximab biodistribution and CD30 expression
Time frame: 2 years
Relation between 89Zr-brentuximab tracer uptake and CD30 protein expression
1 secondary outcome
Relation between 89Zr-brentuximab uptake and response to therapy
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2024.
- Individual participant dataSharing planned: No. all IPD that underlie results in a publication
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marcel Nijland, MD principal investigator
UMCGoningen
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Brentuximab vedotin in people with Diffuse Large B-cell-lymphoma, run by University Medical Center Groningen.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Marijn de Vries (0610013023, m.l.de.vries@umcg.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
An optimized 89Zr-brentuximab imaging protocol for visualisation of CD30 distribution by PET-scan (time frame: 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jan 2024.