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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04685616




Registration number
NCT04685616
Ethics application status
Date submitted
27/11/2020
Date registered
28/12/2020

Titles & IDs
Public title
Brentuximab Vedotin in Early Stage Hodgkin Lymphoma
Scientific 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
Secondary ID [1] 0 0
2020-005160-65
Secondary ID [2] 0 0
RADAR
Universal Trial Number (UTN)
Trial acronym
RADAR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hodgkin Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Hodgkin's

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Involved site radiotherapy
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Bleomycin
Treatment: Drugs - Brentuximab vedotin
Treatment: Drugs - Vinblastine
Treatment: Drugs - Dacarbazine
Treatment: Drugs - Haematopoietic growth factor

Active comparator: ABVD +/- ISRT - 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.

Experimental: A2VD +/- ISRT - 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.


Treatment: Other: Involved site radiotherapy
Involved site radiotherapy as per International Lymphoma Radiation Oncology Group (ILROG) guidelines.

Recommended dose 30Gy

Treatment: Drugs: Doxorubicin
See arm description

Treatment: Drugs: Bleomycin
See arm description

Treatment: Drugs: Brentuximab vedotin
See arm description

Treatment: Drugs: Vinblastine
See arm description

Treatment: Drugs: Dacarbazine
See arm description

Treatment: Drugs: Haematopoietic growth factor
See arm description
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression free survival (PFS)
Timepoint [1] 0 0
3 years from end of treatment
Secondary outcome [1] 0 0
PET-CMR (complete metabolic response) rate
Timepoint [1] 0 0
At the end of cycle 2 (each cycle is 28 days)
Secondary outcome [2] 0 0
Event-free survival (EFS)
Timepoint [2] 0 0
5 years from end of treatment
Secondary outcome [3] 0 0
Overall survival (OS)
Timepoint [3] 0 0
5 years from end of treatment
Secondary outcome [4] 0 0
Incidence of second cancers and cardiovascular disease
Timepoint [4] 0 0
5 years from end of treatment
Secondary outcome [5] 0 0
Safety and toxicity of ABVD and A2VD as described by CTCAE v5.0
Timepoint [5] 0 0
From start of treatment to 30 days post treatment

Eligibility
Key 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
Minimum age
16 Years
Maximum age
69 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/04/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/09/2032
Actual
Sample size
Target
1042
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
Royal North Shore Hospital - Saint Leonards
Recruitment hospital [2] 0 0
Townsville University Hospital - Townsville
Recruitment hospital [3] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [5] 0 0
Royal Brisbane and Women's Hospital - Brisbane
Recruitment hospital [6] 0 0
Royal Darwin Hospital - Darwin
Recruitment hospital [7] 0 0
Sunshine Hospital (Western Health) - Melbourne
Recruitment hospital [8] 0 0
Concord Repatriation General Hospital - Sydney
Recruitment hospital [9] 0 0
St George Hospital - Sydney
Recruitment postcode(s) [1] 0 0
2065 - Saint Leonards
Recruitment postcode(s) [2] 0 0
QLD 4814 - Townsville
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
VIC 3128 - Box Hill
Recruitment postcode(s) [5] 0 0
QLD 4006 - Brisbane
Recruitment postcode(s) [6] 0 0
NT 0810 - Darwin
Recruitment postcode(s) [7] 0 0
VIC 3021 - Melbourne
Recruitment postcode(s) [8] 0 0
NSW 2139 - Sydney
Recruitment postcode(s) [9] 0 0
NSW 2217 - Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
Belgium
State/province [3] 0 0
West Flanders
Country [4] 0 0
Netherlands
State/province [4] 0 0
De Boelelaan 1117
Country [5] 0 0
New Zealand
State/province [5] 0 0
Auckland
Country [6] 0 0
Spain
State/province [6] 0 0
Passeig Maritim 25-29
Country [7] 0 0
Spain
State/province [7] 0 0
Barcelona
Country [8] 0 0
United Kingdom
State/province [8] 0 0
Lancashire
Country [9] 0 0
United Kingdom
State/province [9] 0 0
Newcastle
Country [10] 0 0
United Kingdom
State/province [10] 0 0
Scotland
Country [11] 0 0
United Kingdom
State/province [11] 0 0
Tooting
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Aberdeen
Country [13] 0 0
United Kingdom
State/province [13] 0 0
Bodelwyddan
Country [14] 0 0
United Kingdom
State/province [14] 0 0
Bristol
Country [15] 0 0
United Kingdom
State/province [15] 0 0
Cardiff
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Glasgow
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Hull
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Leicester
Country [19] 0 0
United Kingdom
State/province [19] 0 0
London
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Manchester
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Norwich
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Nottingham
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Oxford
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Plymouth
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Sunderland
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Sutton
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Torquay
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Truro

Funding & Sponsors
Primary sponsor type
Other
Name
University College, London
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Takeda
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
University of Miami
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
European Organisation for Research and Treatment of Cancer - EORTC
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Australasian Leukaemia and Lymphoma Group
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Commercial sector/industry
Name [5] 0 0
Seagen Inc.
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
Canadian Cancer Trials Group
Address [6] 0 0
Country [6] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
John Radford
Address 0 0
University of Manchester / Christie Hospital, Manchester
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
RADAR Trial Coordinator
Address 0 0
Country 0 0
Phone 0 0
+44(0)207 679 9860
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04685616