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Advanced Hodgkin LymphomaPhase 2COBRANCT03517137

Very Early PET-response Adapted Targeted Therapy for Advanced Hodgkin Lymphoma: a Single -Arm Phase II Study

A Phase 2 study testing Brentuximab Vedotin, Adriamycin and Vinblastine in people with Advanced Hodgkin Lymphoma, run by European Organisation for Research and Treatment of Cancer - EORTC at 16 sites in 7 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The main objective of this trial is to assess whether treatment adaptation based on a very early FDG-PET/CT results in improved efficacy while minimizing treatment toxicity in advanced stage Hodgkin Lymphoma (HL) patients treated with brentuximab vedotin (BV)-containing regimens. Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
Advanced Hodgkin Lymphoma
What is being tested?
Brentuximab Vedotin, Adriamycin and Vinblastine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
150 participants
Where
16 sitesin 7 countries
Study dates
1 Aug 2019to 16 Nov 2026
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Previously untreated, histologically proven classical Hodgkin lymphoma;
  • Staged by PET with diagnostic-quality CT (i.v. contrast).
  • Clinical stages according to Lugano 2014 and based on FDG/PET CT:
  • Stage IIB with large mediastinal mass > 1/3 max transverse diameter thorax and/or extranodal lesion(s)
  • Stage III - IV
  • Consent to participation in translational research:
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  • Archival tumor tissue available (15 blank formalin fixed paraffin embedded tissue samples mounted on APES slides or a tissue block).
  • Women of child bearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours prior to the first dose of study treatment.
  • Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 6 months after the last dose of treatment. A highly effective method of birth control is defined as a method which results in a low failure rate (i.e. less than 1 percent per year) when used consistently and correctly.
  • Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 6 months after the last study treatment.
  • Absence of any medical, psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
  • Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations.

Who cannot join

  • Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of Progressive Multifocal Leukoencenphalopathy
  • Symptomatic neurologic disease compromising normal activities of daily living or requiring medications
  • Sensory or motor peripheral neuropathy greater than or equal to grade 2 according to CTCAE version 4.0
  • Any of the following cardiovascular conditions or values:
  • within 6 months before registration:
  • A left-ventricular ejection fraction <50 percent (at registration)
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  • New York Heart Association (NYHA) Class III or IV heart failure.
  • Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  • symptomatic coronary heart disease (stable angina pectoris is allowed)
  • severe uncontrolled hypertension within 2 years before registration
  • Myocardial infarction
  • Patients with poorly controlled diabetes mellitus (HbA1c > 7.5 percent or a fasting blood sugar > 200 mg/dL).
  • Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks prior to registration.
  • Known HIV infection, chronic active hepatitis C, HBV positivity (HBsAg + patients; HBsAg -/HBcAb+/HBV DNA+ patients).
  • Note: HBsAg-/HBV DNA - patients are eligible; patients who are seropositive due to vaccination are eligible
  • Concomitant or previous malignancies within the past 5 years with the exception of adequately treated carcinoma in situ of the cervix , nonmelanoma skin cancer.
  • Previous treatment with anti CD30 antibodies
  • Known hypersensitivity to any excipient contained in Brentuximab Vedotin formulation and other study drugs. Refer to Summary Product Characteristics for list of excipients.
  • Concurrent anti-cancer treatment or use of any investigational agent(s)

Trial locations and contacts

16 sites in 7 countries.

16 sites in 7 countries

Netherlands7 sites

  • Amsterdam UMC - Locatie AMC

    Amsterdam, 1105

  • Deventer Ziekenhuis

    Deventer, 7400

  • University Medical Center Groningen

    Groningen, 9713

  • Medisch Centrum Leeuwarden-Zuid

    Leeuwarden, 8934

  • Haaglanden Medisch Centrum (HMC) - Haaglanden MC - locatie Antoniushove

    Leidschendam, 2262

  • Radboudumc - Radboud University Medical Center Nijmegen

    Nijmegen, 6525

  • Erasmus MC

    Rotterdam, 3015

Other trials in Netherlands

Belgium3 sites

  • ZNA Stuivenberg

    Antwerp, 2060

  • Universitair Ziekenhuis Antwerpen

    Edegem, 2650

  • U.Z. Leuven - Campus Gasthuisberg

    Leuven, 3000

Other trials in Belgium

Spain2 sites

  • Hospital Duran i Reynals (Institut Catala D'Oncologia)

    L'Hospitalet de Llobregat, 08908

  • Complejo Hospitalario de Navarra

    Pamplona, 31008

Other trials in Spain

Denmark1 site

  • University Hospitals Copenhagen - Rigshospitalet

    Copenhagen, 2100

Other trials in Denmark

Poland1 site

  • Maria Sklodowska Curie National Institute of Oncology - National Research Institute

    Warsaw, 02781

Other trials in Poland

Portugal1 site

  • Instituto Portugues De Oncologia - Francisco Gentil - Centro De Lisboa

    Lisbon, 1099

Other trials in Portugal

Slovakia1 site

  • National Cancer Institute

    Bratislava, 833

Other trials in Slovakia

About this study

The main objective of this trial is to assess whether treatment adaptation based on a very early FDG-PET/CT results in improved efficacy while minimizing treatment toxicity in advanced stage Hodgkin Lymphoma (HL) patients treated with brentuximab vedotin (BV)-containing regimens.

Read the detailed description

This single-arm phase II study investigates the value of early FDG-PET-response adapted BV-based therapy for advanced HL. All patients will receive one cycle of BrAVD followed by an FDG-PET/CT. Patients with a negative early FDG-PET(Deauville score 1-3) will continue with five more BrAVD cycles (total six cycles) while patients with a positive FDG-PET should shift to six cycles of BrECADD.

The hypothesis is that the efficacy will be comparable to the efficacy of BEACOPPesc and BrECADD, while using the intensive chemotherapy regimen only for those patients who do not achieve a negative FDG-PET after one cycle.

The choice to assess the treatment sensitivity by PET after a single cycle of BrAVD is based on results from a recent international multicenter study comparing FDG-PET/CT after one and two cycles of ABVD chemotherapy in HL. There is no reason to suspect that FDG-PET1 should be less prognostic after BrAVD than after ABVD.

With this trial, the investigators believe they can add important information about the optimal treatment of BV-containing first-line treatment for advanced HL, and thus answer important therapeutic questions that are likely to otherwise remain unanswered even after the Echelon-1 and HD21 trials reach mature results. This relatively large single-arm phase II trial of 150 patients will allow a meaningful comparison with the BrAVD and BrECADD regimens based on modified progression-free survival (primary endpoint) and progression-free survival (secondary endpoint) respectively.

Being tested
Brentuximab Vedotin, Adriamycin, Vinblastine, Dacarbazine, Etoposide
Keywords
advanced Hodgkin lymphoma, brentuximab vedotin, phase 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Brentuximab VedotinDrug

    For PET positive (score of 4-5 following Deauville Criteria) patients: Brentuximab vedotin is administered as an IV infusion over a period of 30 minutes at 1.8 mg/kg on day 1, every 3 weeks (6 cycles); For PET negative (score of 1-3 following Deauville Criteria) patients: Brentuximab vedotin is administered as an IV infusion over a period of 30 minutes at 1.2 mg/kg on day 1 and 15, every 4 weeks (5 cycles)

  • AdriamycinDrug

    For PET positive (score of 4-5 following Deauville Criteria) patients: Adriamycin is administered as an IV infusion over a period of 15 minutes at 40 mg/m² on day 2, every 3 weeks (6 cycles); For PET negative (score of 1-3 following Deauville Criteria) patients: Adriamycin is administered as an IV infusion over a period of 15 minutes at 25 mg/m² on day 1 and 15, every 4 weeks (5 cycles)

  • VinblastineDrug

    For PET negative (score of 1-3 following Deauville Criteria) patients: Vinblastine is administered as an IV infusion over a period of 15 minutes at 6mg/m² on day 1 and 15, every 4 weeks (5 cycles)

  • DacarbazineDrug

    For PET positive (score of 4-5 following Deauville Criteria) patients: Dacarbazine is administered as an IV infusion over a period of 60 minutes at 250 mg/m² on day 3 and 4, every 3 weeks (6 cycles); For PET negative (score of 1-3 following Deauville Criteria) patients: Dacarbazine is administered as an IV infusion over a period of 60 minutes at 375 mg/m² on day 1 and 15, every 4 weeks (5 cycles)

  • EtoposideDrug

    For PET positive (score of 4-5 following Deauville Criteria) patients: Etoposide is administered as an IV infusion over a period of 60 minutes at 150 mg/m² on day 2,3 and 4, every 3 weeks (6 cycles)

  • CyclophosphamideDrug

    For PET positive (score of 4-5 following Deauville Criteria) patients: Cyclophosphamide is administered as an IV infusion over a period of 30 minutes at 1250 mg/m² on day 2, every 3 weeks (6 cycles)

  • Radiation TherapyRadiation

    Patients with residual lymphoma mass(es) showing metabolic activity of Deauville score 4 or 5 after completion of chemotherapy will be offered consolidation radiotherapy.

Study groups in NCT03517137
Study groupRoleWhat they receive
TreatmentExperimentalNot described
Receives: Drug: Brentuximab Vedotin; Drug: Adriamycin; Drug: Vinblastine; Drug: Dacarbazine; Drug: Etoposide; Drug: Cyclophosphamide; Radiation: Radiation Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Modified Progression-free Survival (mPFS) Rate at 2 Years

    Modified PFS (mPFS) is defined as the time interval between the date of treatment start and the date of the first of:

    • Progressive disease (PD)
    • Start of new treatment for Classical Hodgkin Lymphoma (cHL) when not in Complete Response at the end of protocol treatment; in this case, the date of mPFS is the date of the FDG-PET/CT scan at the end of protocol treatment. Switching therapy prior to end of protocol treatment for reasons other than Progressive Disease is not considered an event for mPFS. "End of protocol treatment" refers to completion of the planned protocol treatment with no more than 1 missed cycle, including radiotherapy on PET positive lesions if administered
    • Death due to any cause

    Measured: 2 years from the date of treatment start

Secondary outcomes (3)

  1. Proportion of Patients With a Negative FDG-PET

    It will be assessed how many patients have a negative FDG-PET image when taken at the end of their first cycle of BrAVD. The BrAVD cycle lasts 4 weeks.

    Measured: At day 22 to 23 from start of treatment (day 1 = date of start of treatment)

  2. Progression-free Survival (PFS) Rate at 2 Years

    Progression-free survival

    Measured: 2 years from the date of treatment start

  3. Overall Survival Rate at 2 Years

    Overall survival

    Measured: 2 years from the date of treatment start

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 May 2018
  2. Study start1 Aug 2019
  3. Primary completion28 Aug 2023
  4. Study completion16 Nov 2026 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
150 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03517137
Sponsor's protocol ID
EORTC-1537-LYMG
Acronym
COBRA
Status last verified
Sep 2026
First submitted
5 Apr 2018
Last updated
11 Sep 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Hutchings M, Diepstra A, Sureda Balari A, Carvalho S, Vranovsky A, Noordzij W, Loft A, Arens A, Teesink S, Visser L, Stevens W, Aleman BMP, Woei-A-Jin FJSH, Viguria M, Saevels K, Te Boome L, Tonino S, Meijnders P, Domingo Domenech E, Hasselbalch Riley C, Musekera L, Nuyens S, Mallien C, Sents W, Buhrer E, Fortpied C, Plattel WJ. Very early [18F]FDG-PET-guided targeted therapy in untreated advanced-stage classic Hodgkin lymphoma (EORTC-1537-COBRA): primary results of a single-arm, multicentre, phase 2 trial. Lancet Haematol. 2026 May;13(5):e274-e283. doi: 10.1016/S2352-3026(26)00068-2.

    PubMed 42069408

  • Kreuzberger N, Goldkuhle M, von Tresckow B, Kobe C, Sickinger MT, Monsef I, Skoetz N. Positron emission tomography-adapted therapy for first-line treatment in adults with Hodgkin lymphoma. Cochrane Database Syst Rev. 2025 Mar 26;3(3):CD010533. doi: 10.1002/14651858.CD010533.pub3.

    PubMed 40135712

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Brentuximab Vedotin, Adriamycin and Vinblastine in people with Advanced Hodgkin Lymphoma, run by European Organisation for Research and Treatment of Cancer - EORTC at 16 sites in 7 countries.

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 12 inclusion and 19 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: under way, not looking for participants, as of the sponsor's last update on 11 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in Netherlands, Belgium, Spain, Denmark, Poland and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Modified Progression-free Survival (mPFS) Rate at 2 Years (time frame: 2 years from the date of treatment start). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03517137, which also lists 2 linked publications.

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 11 Sep 2026.

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