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Brentuximab Vedotin in Early Stage Hodgkin Lymphoma

NCT04685616 · University College, London
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Official title
A Randomised Phase III Trial With a PET Response Adapted Design Comparing ABVD +/- ISRT With A2VD +/- ISRT in Patients With Previously Untreated Stage IA/IIA Hodgkin Lymphoma
About this study
Eligible patients will be randomised to receive either ABVD chemotherapy (doxorubicin, bleomycin, vinblastine and dacarbazine) or A2VD chemotherapy (doxorubicin, brentuximab vedotin, vinblastine and dacarbazine, with growth factor support). If patients agree, they will have a PET-CT scan after 1 cycle (PET1). The result of this scan will be blinded and used for exploratory endpoints only. Treatment will not be influenced by the result of this scan. All patients will have a PET-CT scan after 2 cycles of treatment (PET2) which will be centrally reviewed. The Deauville score from central review will be used to risk adapt subsequent therapy as follows: * Patients with Deauville score 1-3 will have one further cycle of their randomised chemotherapy and then enter follow up. * Patients with Deauville score 4 will have two further cycles of their randomised chemotherapy followed by involved site radiotherapy * Patients with Deauville score 5 will be withdrawn from trial treatment. They will have further treatment at their treating clinician's discretion and will enter follow up for the trial. Patients with Deauville score 4 on PET2 will have a final PET-CT scan to confirm adequate treatment response. Patients will be followed up for a minimum of 5 years after completing treatment.
Eligibility criteria
Inclusion Criteria: * Males and females aged 16-69 years (inclusive) (age range is 18-69 in US and EU) * Histologically confirmed classical Hodgkin lymphoma * Stage I or II supradiaphragmatic disease with no mediastinal bulk disease (defined as greater than a third of the transthoracic diameter at any level of thoracic vertebra as determined by CT) or B symptoms. Bulky disease at other sites is acceptable. Extranodal disease (single extranodal site (stage I) or contiguous nodal extension (stage II)) is acceptable. * ECOG performance status 0-2. * No previous treatment for Hodgkin lymphoma * Fit to receive anthracycline-based chemotherapy (patients with a history of ischaemic heart disease or hypertension should have a left ventricular ejection fraction of ≥50%) * Creatinine clearance (measured or calculated \>40ml/min * Total bilirubin \<1.5 x upper limit of normal, unless attributable to disease or known Gilbert's syndrome * ALT or AST \< 2 x upper limit of normal * Adequate bone marrow function with neutrophils ≥1.0x10\^9/l and platelets ≥100x10\^9/l * Haemoglobin ≥8g/dL * Willing and able to comply with the requirements of the protocol, including contraceptive advice, where applicable * Written informed consent Exclusion Criteria: * Previous treatment for Hodgkin lymphoma, excluding short courses of oral corticosteroids at a dose of 100mg prednisolone (or equivalent) for up to 7 days * Infradiaphragmatic disease * Nodular lymphocyte predominant Hodgkin lymphoma * Absence of FDG-avid lesions on baseline PET scan * Age 70 years or over or age 15 years or under * Other cancer diagnosed with the last 5 years. Patients with completely excised carcinoma in situ of any type and basal or squamous cell carcinoma of the skin are not excluded * Recurrent or persistent other cancer within last 5 years irrespective of date of initial diagnosis * Pre-existing grade ≥1 sensory or motor neuropathy from any cause * History of or current progressive multi-focal leukoencephalopathy or other chronic condition of the brain * Symptomatic neurologic disease compromising normal activities of daily living or requiring medications * Infection with HIV, hepatitis C or active hepatitis B infection (surface antigen or DNA positive) * Any active systemic viral, bacterial or fungal infection requiring systemic antibiotics, antivirals or antifungals within 2 weeks prior to first trial drug dose * Receiving or recently treated with any other investigational agent (within 4 weeks of trial entry) * Pregnant or breastfeeding women * Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin or any component of ABVD * Known history of any cardiovascular or respiratory conditions that would preclude anthracycline or bleomycin administration * Other significant medical or psychiatric comorbidity that in the opinion of the investigator would make administration of ABVD or A2VD hazardous
Study design
Enrollment target: 1042 participants
Allocation: randomized
Masking: none
Age groups: child, adult, older_adult
Timeline
Starts: 2022-04-14
Estimated completion: 2032-09
Last updated: 2026-07-08
Interventions
Radiation: Involved site radiotherapyDrug: DoxorubicinDrug: BleomycinDrug: Brentuximab vedotinDrug: VinblastineDrug: DacarbazineDrug: Haematopoietic growth factor
Primary outcomes
  • Progression free survival (PFS) (3 years from end of treatment)
Sponsor
University College, London · other
With: Takeda, University of Miami, European Organisation for Research and Treatment of Cancer - EORTC, Australasian Leukaemia and Lymphoma Group, Seagen Inc., Canadian Cancer Trials Group
Contacts & investigators
ContactRADAR Trial Coordinator · contact · ctc.radar@ucl.ac.uk · +44(0)207 679 9860
InvestigatorJohn Radford · principal_investigator, University of Manchester / Christie Hospital, Manchester
All locations (72)
Stanford University - (Stanford Cancer Institute)Recruiting
Stanford, California, United States
University of Miami School of MedicineRecruiting
Miami, Florida, United States
Memorial Sloan Kettering Cancer CenterRecruiting
New York, New York, United States
Royal North Shore HospitalRecruiting
Saint Leonards, New South Wales, Australia
Townsville University HospitalRecruiting
Townsville, Queensland, Australia
Royal Adelaide HospitalRecruiting
Adelaide, Australia
Box Hill HospitalRecruiting
Box Hill, Australia
Royal Brisbane and Women's HospitalRecruiting
Brisbane, Australia
Royal Darwin HospitalRecruiting
Darwin, Australia
Liverpool HospitalRecruiting
Liverpool, Australia
Sunshine Hospital (Western Health)Recruiting
Melbourne, Australia
Concord Repatriation General HospitalRecruiting
Sydney, Australia
St George HospitalRecruiting
Sydney, Australia
AZ Delta Campus RumbekeRecruiting
Roeselare, West Flanders, Belgium
Universitair Ziekenhuis AntwerpenRecruiting
Antwerp, Belgium
Ziekenhuis Netwerk AntwerpenRecruiting
Antwerp, Belgium
UZ LeuvenRecruiting
Leuven, Belgium
CHU-UCL NamurRecruiting
Namur, Belgium
QEII Health Sciences CentreRecruiting
Halifax, Nova Scotia, Canada
Juravinski Cancer CentreRecruiting
Hamilton, Ontario, Canada
Ottowa Hospital Research InstituteRecruiting
Ottawa, Canada
Saint John Regional HospitalRecruiting
Saint John, Canada
University Health Network Princess Margaret Cancer CentreRecruiting
Toronto, Canada
Vancouver Cancer CentreRecruiting
Vancouver, Canada
CancerCare ManitobaRecruiting
Winnipeg, Canada
Aarhus University Hospitak SkjebyRecruiting
Aarhus, Denmark
RigshospitaletRecruiting
Copenhagen, Denmark
St James's HospitalRecruiting
Dublin, Ireland
St. Vincent's University HospitalRecruiting
Dublin, Ireland
University Hospital GalwayRecruiting
Galway, Ireland
Amsterdam UMC - location VUMCRecruiting
Amsterdam, Netherlands
Reinier de Graafweg 3-11 - Postbus 5011 - 2625 AD DelftRecruiting
Delft, Netherlands
Universitair Medisch Centrum GroningenRecruiting
Groningen, Netherlands
Radboud University Medical Center NijmegenRecruiting
Nijmegen, Netherlands
NL 331 - Haaglanden Medisch Centrum (HMC) - Haaglanden MCRecruiting
The Hague, Netherlands
Auckland City HospitalRecruiting
Auckland, New Zealand
Instituto Portugues de Oncologia de Lisboa Francisco GentilRecruiting
Lisbon, Portugal
Narodny Onkologicky UstavRecruiting
Bratislava, Slovakia
Hospital Del MarRecruiting
Barcelona, Spain
Institut Catala d'OncologiaRecruiting
Barcelona, Spain
Complejo Hospitalario de NavarraRecruiting
Pamplona, Spain
Hampshire Hospitals NHS Foundation TrustRecruiting
Basingstoke, Hampshire, United Kingdom
Blackpool Victoria HospitalRecruiting
Blackpool, Lancashire, United Kingdom
Freeman Hospital, NewcastleRecruiting
Newcastle upon Tyne, Newcastle, United Kingdom
LanarkshireRecruiting
Glasgow, Scotland, United Kingdom
St George's HospitalRecruiting
London, Tooting, United Kingdom
Aberdeen Royal InfirmaryRecruiting
Aberdeen, United Kingdom
University Hospitals BirminghamRecruiting
Birmingham, United Kingdom
Glan Clwyd HospitalRecruiting
Bodelwyddan, United Kingdom
Bristol Haematology and Oncology CentreRecruiting
Bristol, United Kingdom
University Hospital of Wales, Cardiff & Vale University Local Health BoardRecruiting
Cardiff, United Kingdom
Colchester Hospital, ESNEFTRecruiting
Colchester, United Kingdom
University Hospital CoventryRecruiting
Coventry, United Kingdom
Beatson West of Scotland Cancer CentreRecruiting
Glasgow, United Kingdom
Castle Hill HospitalRecruiting
Hull, United Kingdom
St James University HospitalRecruiting
Leeds, United Kingdom
University Hospitals of Leicester NHS TrustRecruiting
Leicester, United Kingdom
The Clatterbridge Cancer Centre NHSFT, 65 Pembroke PlaceRecruiting
Liverpool, United Kingdom
St Bartholomew's HospitalRecruiting
London, United Kingdom
University College London Hospitals NHS Foundation Trust (UCLH)Recruiting
London, United Kingdom
Royal Marsden Hospital ChelseaRecruiting
London, United Kingdom
Christie HospitalRecruiting
Manchester, United Kingdom
Norfolk & Norwich University HospitalRecruiting
Norwich, United Kingdom
Nottingham University Hospitals NHSTRecruiting
Nottingham, United Kingdom
Churchill HospitalRecruiting
Oxford, United Kingdom
Derriford HospitalRecruiting
Plymouth, United Kingdom
Royal Hallamshire HospitalRecruiting
Sheffield, United Kingdom
Southampton General HospitalRecruiting
Southampton, United Kingdom
Sunderland Royal HospitalRecruiting
Sunderland, United Kingdom
Royal Marsden HospitalRecruiting
Sutton, United Kingdom
Torbay HospitalRecruiting
Torquay, United Kingdom
Royal Cornwall HospitalRecruiting
Truro, United Kingdom