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NCT04685616PHASE3Recruiting

Brentuximab Vedotin in Early Stage Hodgkin Lymphoma

University College, London

Start Date

4/14/2022

Completion Date

9/1/2032

Summary

RADAR is a multicentre, international, randomised, open-label phase III clinical trial composed of 2 trials running in parallel. Trial 1 will be led and sponsored by University College London (UCL) and conducted in Europe and Australia/New Zealand. Trial 2 will be led by the Canadian Cancer Trials Group (CCTG) and conducted in North America, with CCTG the regulatory sponsor in Canada, and University of Miami the regulatory sponsor and IND holder in the US. Datasets from Trial 1 and Trial 2 will be combined to achieve the total sample size. Data analysis will be performed by UCL and therefore UCL is responsible for the clinicaltrials.gov entry. Eligible patients will be randomised to receive either ABVD or A2VD chemotherapy. An interim PET-CT scan will be performed after 2 cycles of treatment, which will be used to adapt subsequent treatment. Patients will receive a total of 3-4 cycles of chemotherapy and may also receive involved site radiotherapy as consolidation. Patients will be followed up for a minimum of 5 years after treatment.

Detailed Description

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of their randomised chemotherapy followed by involved site radiotherapy * Patients with Deauville score 5 will be withdrawn from trial treatment.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

Age Range: 16 years to 69 years

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

Interventions

RADIATION

Involved site radiotherapy

DRUG

Doxorubicin

DRUG

Bleomycin

DRUG

Brentuximab vedotin

DRUG

Vinblastine

DRUG

Dacarbazine

DRUG

Haematopoietic growth factor

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Conditions

Hodgkin Lymphoma

Locations

Stanford University - (Stanford Cancer Institute)

Stanford, California 94305

United States

University of Miami School of Medicine

Miami, Florida 33136

United States

Memorial Sloan Kettering Cancer Center

New York, New York 10065

United States

Royal North Shore Hospital

Saint Leonards, New South Wales 2065

Australia

Townsville University Hospital

Townsville, Queensland QLD 4814

Australia

Royal Adelaide Hospital

Adelaide, 5000

Australia

Box Hill Hospital

Box Hill, VIC 3128

Australia

Royal Brisbane and Women's Hospital

Brisbane, QLD 4006

Australia

Royal Darwin Hospital

Darwin, NT 0810

Australia

Liverpool Hospital

Liverpool,

Australia

Sunshine Hospital (Western Health)

Melbourne, VIC 3021

Australia

Concord Repatriation General Hospital

Sydney, NSW 2139

Australia

St George Hospital

Sydney, NSW 2217

Australia

AZ Delta Campus Rumbeke

Roeselare, West Flanders Deltalaan 1, 8800

Belgium

Universitair Ziekenhuis Antwerpen

Antwerp,

Belgium

Ziekenhuis Netwerk Antwerpen

Antwerp,

Belgium

UZ Leuven

Leuven,

Belgium

CHU-UCL Namur

Namur,

Belgium

QEII Health Sciences Centre

Halifax, Nova Scotia B3H 3A7

Canada

Juravinski Cancer Centre

Hamilton, Ontario L8V 5C2

Canada

Ottowa Hospital Research Institute

Ottawa, K1Y 4E9

Canada

Saint John Regional Hospital

Saint John, E2L 4L2

Canada

University Health Network Princess Margaret Cancer Centre

Toronto, M5G 2M9

Canada

Vancouver Cancer Centre

Vancouver, V5Z 4E6

Canada

CancerCare Manitoba

Winnipeg, R3E 0V9

Canada

Aarhus University Hospitak Skjeby

Aarhus,

Denmark

Rigshospitalet

Copenhagen,

Denmark

St James's Hospital

Dublin,

Ireland

St. Vincent's University Hospital

Dublin,

Ireland

University Hospital Galway

Galway,

Ireland

Amsterdam UMC - location VUMC

Amsterdam, 1081 HV

Netherlands

Reinier de Graafweg 3-11 - Postbus 5011 - 2625 AD Delft

Delft,

Netherlands

Universitair Medisch Centrum Groningen

Groningen,

Netherlands

Radboud University Medical Center Nijmegen

Nijmegen,

Netherlands

NL 331 - Haaglanden Medisch Centrum (HMC) - Haaglanden MC

The Hague,

Netherlands

Auckland City Hospital

Auckland, 1023

New Zealand

Instituto Portugues de Oncologia de Lisboa Francisco Gentil

Lisbon,

Portugal

Narodny Onkologicky Ustav

Bratislava,

Slovakia

Hospital Del Mar

Barcelona, ES 08003

Spain

Institut Catala d'Oncologia

Barcelona, ES 08908

Spain

Complejo Hospitalario de Navarra

Pamplona,

Spain

Hampshire Hospitals NHS Foundation Trust

Basingstoke, Hampshire RG24 9NA

United Kingdom

Blackpool Victoria Hospital

Blackpool, Lancashire FY3 8NR

United Kingdom

Freeman Hospital, Newcastle

Newcastle upon Tyne, Newcastle NE7 7DN

United Kingdom

Lanarkshire

Glasgow, Scotland G71 8BB

United Kingdom

St George's Hospital

London, Tooting SW17 0QT

United Kingdom

Aberdeen Royal Infirmary

Aberdeen, AB25 2ZN

United Kingdom

University Hospitals Birmingham

Birmingham, B15 2GW

United Kingdom

Glan Clwyd Hospital

Bodelwyddan, LL18 5UJ

United Kingdom

Bristol Haematology and Oncology Centre

Bristol,

United Kingdom

University Hospital of Wales, Cardiff & Vale University Local Health Board

Cardiff, CF14 4XW

United Kingdom

Colchester Hospital, ESNEFT

Colchester, CO4 5JL

United Kingdom

University Hospital Coventry

Coventry, CV2 2DX

United Kingdom

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN

United Kingdom

Castle Hill Hospital

Hull, HU16 5JQ

United Kingdom

St James University Hospital

Leeds, LS9 7TF

United Kingdom

University Hospitals of Leicester NHS Trust

Leicester, LE1 5WW

United Kingdom

The Clatterbridge Cancer Centre NHSFT, 65 Pembroke Place

Liverpool, L7 8YA

United Kingdom

St Bartholomew's Hospital

London, EC1A 7BE

United Kingdom

University College London Hospitals NHS Foundation Trust (UCLH)

London, NW1 2BU

United Kingdom

Royal Marsden Hospital Chelsea

London, SW3 6JZ

United Kingdom

Christie Hospital

Manchester, M20 4BX

United Kingdom

Norfolk & Norwich University Hospital

Norwich, NR4 7UY

United Kingdom

Nottingham University Hospitals NHST

Nottingham, NG51PB

United Kingdom

Churchill Hospital

Oxford, OX3 7LE

United Kingdom

Derriford Hospital

Plymouth, PL6 8DH

United Kingdom

Royal Hallamshire Hospital

Sheffield, S10 2JF

United Kingdom

Southampton General Hospital

Southampton, SO16 6YD

United Kingdom

Sunderland Royal Hospital

Sunderland, SR4 7TP

United Kingdom

Royal Marsden Hospital

Sutton, SM2 5PT

United Kingdom

Torbay Hospital

Torquay, TQ2 7AA

United Kingdom

Royal Cornwall Hospital

Truro, TR1 3LJ

United Kingdom