Brentuximab Vedotin in Early Stage Hodgkin Lymphoma

NCT04685616 | Recruiting Phase 3 DMC FDA Drug

• 6 other identifiers: RADAR2020-005160-65IISR X25041UCL/15/0105CCTG HD.12IRB number 20230081
• Study Type: interventional
• Target: 1,042
• Locations: 12 countries
• Sites: 70

Brief 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.

Conditions

Hodgkin Lymphoma

Keywords

PET-response adapted; Stage IA/IIA Hodgkin lymphoma; Brentuximab vedotin

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  Time from randomisation to first date of progression or death

  3 years from end of treatment

Secondary Outcomes (5)

• PET-CMR (complete metabolic response) rate

  At the end of cycle 2 (each cycle is 28 days)

• Event-free survival (EFS)

  5 years from end of treatment

• Overall survival (OS)

  5 years from end of treatment

• Incidence of second cancers and cardiovascular disease

  5 years from end of treatment

• Safety and toxicity of ABVD and A2VD as described by CTCAE v5.0

  From start of treatment to 30 days post treatment

Other Outcomes (4)

• Prognostic power of PET after 1 and 2 cycles of ABVD/A2VD

  Up to 5 years after end of treatment

• Prognostic and predictive power of baseline PET features

  Up to 3 years after end of treatment

• Change in pulmonary function tests at end of treatment, 1 and 2 years

  3 months & 1 year after end of treatment

Study Arms (2)

ABVD +/- ISRT

ACTIVE COMPARATOR

2 x 28 day cycles of ABVD: Doxorubicin 25mg/m\^2 IV days 1 \& 15 Bleomycin 10000 IU/m\^2 days 1 \& 15 Vinblastine 6mg/m\^2 days 1 \& 15 Dacarbazine 375mg/m\^2 days 1 \& 15 PET-CT after 2 cycles will determine subsequent treatment: Deauville score 1-3 (PET CMR): 1 further cycle of ABVD then follow up Deauville score 4 (PET positive): 2 further cycles of ABVD followed by involved site radiotherapy (ISRT) Deauville score 5: withdraw from trial treatment; further treatment will be given at the treating clinician's discretion. Enter follow up for the trial.

Radiation: Involved site radiotherapy; Drug: Doxorubicin; Drug: Bleomycin; Drug: Vinblastine; Drug: Dacarbazine

A2VD +/- ISRT

EXPERIMENTAL

2 x 28 day cycles of A2VD: Doxorubicin 25mg/m\^2 IV days 1 \& 15 Brentuximab vedotin 1.2mg/kg (max 120mg) days 1 \& 15 Vinblastine 6mg/m\^2 days 1 \& 15 Dacarbazine 375mg/m\^2 days 1 \& 15 Filgrastim (or equivalent haematopoietic growth factor) for 5-7 days from day 2 and day 16 (or single dose of peg-filgrastim on days 2 \& 16) PET-CT after 2 cycles will determine subsequent treatment: Deauville score 1-3 (PET CMR): 1 further cycle of A2VD then follow up Deauville score 4 (PET positive): 2 further cycles of A2VD followed by involved site radiotherapy (ISRT) Deauville score 5: withdraw from trial treatment; further treatment will be given at the treating clinician's discretion. Enter follow up for the trial.

Radiation: Involved site radiotherapy; Drug: Doxorubicin; Drug: Brentuximab vedotin; Drug: Vinblastine; Drug: Dacarbazine; Drug: Haematopoietic growth factor

Interventions

Involved site radiotherapy RADIATION

Involved site radiotherapy as per International Lymphoma Radiation Oncology Group (ILROG) guidelines. Recommended dose 30Gy

A2VD +/- ISRT; ABVD +/- ISRT

Doxorubicin DRUG

See arm description

A2VD +/- ISRT; ABVD +/- ISRT

Bleomycin DRUG

See arm description

ABVD +/- ISRT

Brentuximab vedotin DRUG

See arm description

A2VD +/- ISRT

Vinblastine DRUG

See arm description

A2VD +/- ISRT; ABVD +/- ISRT

Dacarbazine DRUG

See arm description

A2VD +/- ISRT; ABVD +/- ISRT

Haematopoietic growth factor DRUG

See arm description

Also known as: Filgrastim, G-CSF, Pegfilgrastim

A2VD +/- ISRT

Eligibility Criteria

• Age: 16 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: collaborator
• University College, London: lead
• Takeda: collaborator
• University of Miami: collaborator
• Australasian Leukaemia and Lymphoma Group: collaborator
• Seagen Inc.: collaborator
• Canadian Cancer Trials Group: collaborator

Study Sites (70)

Stanford University - (Stanford Cancer Institute)

Stanford, California, 94305, United States

RECRUITING

University of Miami School of Medicine

Miami, Florida, 33136, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Royal North Shore Hospital

Saint Leonards, New South Wales, 2065, Australia

RECRUITING

Townsville University Hospital

Townsville, Queensland, QLD 4814, Australia

RECRUITING

Royal Adelaide Hospital

Adelaide, 5000, Australia

RECRUITING

Box Hill Hospital

Box Hill, VIC 3128, Australia

RECRUITING

Royal Brisbane and Women's Hospital

Brisbane, QLD 4006, Australia

RECRUITING

Royal Darwin Hospital

Darwin, NT 0810, Australia

RECRUITING

Liverpool Hospital

Liverpool, Australia

RECRUITING

Sunshine Hospital (Western Health)

Melbourne, VIC 3021, Australia

RECRUITING

Concord Repatriation General Hospital

Sydney, NSW 2139, Australia

RECRUITING

St George Hospital

Sydney, NSW 2217, Australia

RECRUITING

AZ Delta Campus Rumbeke

Roeselare, West Flanders, Deltalaan 1, 8800, Belgium

RECRUITING

Universitair Ziekenhuis Antwerpen

Antwerp, Belgium

RECRUITING

Ziekenhuis Netwerk Antwerpen

Antwerp, Belgium

RECRUITING

UZ Leuven

Leuven, Belgium

RECRUITING

CHU-UCL Namur

Namur, Belgium

RECRUITING

QEII Health Sciences Centre

Halifax, Nova Scotia, B3H 3A7, Canada

RECRUITING

Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

RECRUITING

Ottowa Hospital Research Institute

Ottawa, K1Y 4E9, Canada

RECRUITING

Saint John Regional Hospital

Saint John, E2L 4L2, Canada

RECRUITING

University Health Network Princess Margaret Cancer Centre

Toronto, M5G 2M9, Canada

RECRUITING

Vancouver Cancer Centre

Vancouver, V5Z 4E6, Canada

RECRUITING

CancerCare Manitoba

Winnipeg, R3E 0V9, Canada

RECRUITING

Aarhus University Hospitak Skjeby

Aarhus, Denmark

RECRUITING

Rigshospitalet

Copenhagen, Denmark

RECRUITING

St James's Hospital

Dublin, Ireland

RECRUITING

University Hospital Galway

Galway, Ireland

RECRUITING

Amsterdam UMC - location VUMC

Amsterdam, 1081 HV, Netherlands

RECRUITING

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

Delft, Netherlands

RECRUITING

Universitair Medisch Centrum Groningen

Groningen, Netherlands

RECRUITING

Radboud University Medical Center Nijmegen

Nijmegen, Netherlands

RECRUITING

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

The Hague, Netherlands

RECRUITING

Auckland City Hospital

Auckland, 1023, New Zealand

RECRUITING

Instituto Portugues de Oncologia de Lisboa Francisco Gentil

Lisbon, Portugal

RECRUITING

Narodny Onkologicky Ustav

Bratislava, Slovakia

RECRUITING

Hospital Del Mar

Barcelona, ES 08003, Spain

RECRUITING

Institut Catala d'Oncologia

Barcelona, ES 08908, Spain

RECRUITING

Complejo Hospitalario de Navarra

Pamplona, Spain

RECRUITING

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

Cardiff, Cardiff, CF14 4XW, United Kingdom

RECRUITING

Blackpool Victoria Hospital

Blackpool, Lancashire, FY3 8NR, United Kingdom

RECRUITING

Freeman Hospital, Newcastle

Newcastle upon Tyne, Newcastle, NE7 7DN, United Kingdom

RECRUITING

Nottingham University Hospitals NHST

Nottingham, Nottingham, NG51PB, United Kingdom

RECRUITING

Lanarkshire

Glasgow, Scotland, G71 8BB, United Kingdom

RECRUITING

St George's Hospital

London, Tooting, SW17 0QT, United Kingdom

RECRUITING

Aberdeen Royal Infirmary

Aberdeen, AB25 2ZN, United Kingdom

RECRUITING

University Hospitals Birmingham

Birmingham, B15 2GW, United Kingdom

RECRUITING

Glan Clwyd Hospital

Bodelwyddan, LL18 5UJ, United Kingdom

RECRUITING

Bristol Haematology and Oncology Centre

Bristol, United Kingdom

RECRUITING

Colchester Hospital, ESNEFT

Colchester, CO4 5JL, United Kingdom

RECRUITING

University Hospital Coventry

Coventry, CV2 2DX, United Kingdom

RECRUITING

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

RECRUITING

Castle Hill Hospital

Hull, HU16 5JQ, United Kingdom

RECRUITING

St James University Hospital

Leeds, LS9 7TF, United Kingdom

RECRUITING

University Hospitals of Leicester NHS Trust

Leicester, LE1 5WW, United Kingdom

RECRUITING

The Clatterbridge Cancer Centre NHSFT, 65 Pembroke Place

Liverpool, L7 8YA, United Kingdom

RECRUITING

St Bartholomew's Hospital

London, EC1A 7BE, United Kingdom

RECRUITING

University College London Hospitals NHS Foundation Trust (UCLH)

London, NW1 2BU, United Kingdom

RECRUITING

Royal Marsden Hospital Chelsea

London, SW3 6JZ, United Kingdom

RECRUITING

Christie Hospital

Manchester, M20 4BX, United Kingdom

RECRUITING

Norfolk & Norwich University Hospital

Norwich, NR4 7UY, United Kingdom

RECRUITING

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

RECRUITING

Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

RECRUITING

Royal Hallamshire Hospital

Sheffield, S10 2JF, United Kingdom

RECRUITING

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

RECRUITING

Sunderland Royal Hospital

Sunderland, SR4 7TP, United Kingdom

RECRUITING

Royal Marsden Hospital

Sutton, SM2 5PT, United Kingdom

RECRUITING

Torbay Hospital

Torquay, TQ2 7AA, United Kingdom

RECRUITING

Royal Cornwall Hospital

Truro, TR1 3LJ, United Kingdom

RECRUITING

Related Publications (1)

• 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.

  PMID: 40135712 DERIVED

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Doxorubicin; Bleomycin; Brentuximab Vedotin; Vinblastine; Dacarbazine; Filgrastim; Granulocyte Colony-Stimulating Factor; pegfilgrastim

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Glycopeptides; Glycoconjugates; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Colony-Stimulating Factors; Glycoproteins; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Biological Factors

Study Officials

• John Radford

  University of Manchester / Christie Hospital, Manchester

  PRINCIPAL INVESTIGATOR

Central Study Contacts

RADAR Trial Coordinator

CONTACT

+44(0)207 679 9860; ctc.radar@ucl.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2020
• First Posted: December 28, 2020
• Study Start: April 14, 2022
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): September 1, 2032
• Last Updated: March 30, 2026

Record last verified: 2026-03

Locations

IE (2); PT (1); AU (10); CA (7); DK (2); NL (5); BE (5); NZ (1); SL (1); US (3); GB (30); ES (3)