Brentuximab Vedotin in Early Stage Hodgkin Lymphoma

Hodgkin Lymphoma Clinical Trial

— RADAR  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04685616
• Other study ID #: RADAR
• Secondary ID: 2020-005160-65II
• Status: Recruiting
• Phase: Phase 3
• Start date: April 14, 2022
• Est. completion date: September 2032

Study information

• Verified date: May 2024
• Source: University College, London
• Contact: RADAR Trial Coordinator
• Phone: +44(0)207 679 9860
• Email: ctc.radar[@]ucl.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1042
• Est. completion date: September 2032
• Est. primary completion date: September 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 69 Years

Eligibility

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

Related Conditions & MeSH terms

• Hodgkin Disease
• Hodgkin Lymphoma
• Lymphoma

Intervention

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

Drug:
• Doxorubicin
See arm description
• Bleomycin
See arm description
• Brentuximab vedotin
See arm description
• Vinblastine
See arm description
• Dacarbazine
See arm description
• Haematopoietic growth factor
See arm description

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide
Australia	Box Hill Hospital	Box Hill
Australia	Royal Brisbane and Women's Hospital	Brisbane
Australia	Royal Darwin Hospital	Darwin
Australia	Sunshine Hospital (Western Health)	Melbourne
Australia	Royal North Shore Hospital	Saint Leonards	New South Wales
Australia	Concord Repatriation General Hospital	Sydney
Australia	St George Hospital	Sydney
Australia	Townsville University Hospital	Townsville	Queensland
Belgium	AZ Delta Campus Rumbeke	Roeselare	West Flanders
New Zealand	Auckland City Hospital	Auckland
Spain	Hospital Del Mar	Barcelona	Passeig Maritim 25-29
United Kingdom	Aberdeen Royal Infirmary	Aberdeen
United Kingdom	Blackpool Victoria Hospital	Blackpool	Lancashire
United Kingdom	Glan Clwyd Hospital	Bodelwyddan
United Kingdom	Bristol Haematology and Oncology Centre	Bristol
United Kingdom	University Hospital of Wales, Cardiff & Vale University Local Health Board	Cardiff
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Lanarkshire	Glasgow	Scotland
United Kingdom	Castle Hill Hospital	Hull
United Kingdom	University Hospitals of Leicester NHS Trust	Leicester
United Kingdom	St Bartholomew's Hospital	London
United Kingdom	St George's Hospital	London	Tooting
United Kingdom	University College London Hospitals NHS Foundation Trust (UCLH)	London
United Kingdom	Christie Hospital	Manchester
United Kingdom	Freeman Hospital, Newcastle	Newcastle Upon Tyne	Newcastle
United Kingdom	Norfolk & Norwich University Hospital	Norwich
United Kingdom	Nottingham University Hospitals NHST	Nottingham
United Kingdom	Churchill Hospital	Oxford
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	Sunderland Royal Hospital	Sunderland
United Kingdom	Royal Marsden Hospital	Sutton
United Kingdom	Torbay Hospital	Torquay
United Kingdom	Royal Cornwall Hospital	Truro
United States	University of Miami School of Medicine	Miami	Florida

Sponsors (7)

Lead Sponsor	Collaborator
University College, London	Australasian Leukaemia and Lymphoma Group, Canadian Cancer Trials Group, European Organisation for Research and Treatment of Cancer - EORTC, Seagen Inc., Takeda, University of Miami

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  New Zealand,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Prognostic power of PET after 1 and 2 cycles of ABVD/A2VD	7A Associations between PET1 Deauville score (DS) and PET2 DS; 7B Associations between PET1 DS and EFS; 7C Associations between PET1 DS and OS; 7D Associations between PET1 DS and PFS; 7E Associations between PET2 DS and EFS; 7F Associations between PET2 DS and OS; 7G Associations between PET2 DS and PFS; 7H Associations between EORTC baseline stratification and PET1 DS; 7I Associations between EORTC baseline stratification and PET2 DS; 7J Associations between EORTC baseline stratification and EFS; 7K Associations between EORTC baseline stratification and OS; 7L Associations between EORTC baseline stratification and EFS; 7M Associations between GHSG baseline stratification and PET1 DS; 7N Associations between GHSG baseline stratification and PET2 DS; 7O Associations between GHSG baseline stratification and EFS; 7P Associations between GHSG baseline stratification and OS; 7Q Associations between GHSG baseline stratification and EFS	Up to 5 years after end of treatment
Other	Prognostic and predictive power of baseline PET features	The association of baseline quantitative PET parameters such as total lesion glycolysis (TLG) and PFS/EFS/OS will be assessed. The ability to predict PET score (PET1 and PET2) and Hodgkin lymphoma events within 3 years will be compared: 8A Associations between baseline quantitative PET parameters such as total lesion glycolysis (TLG) and PFS; 8B Associations between baseline quantitative PET parameters such as total lesion glycolysis (TLG) and OS; 8C Associations between baseline quantitative PET parameters such as total lesion glycolysis (TLG) and EFS; 8D Associations between baseline quantitative PET parameters such as total lesion glycolysis (TLG) and PET1 DS; 8E Associations between baseline quantitative PET parameters such as total lesion glycolysis (TLG) and PET2 DS	Up to 3 years after end of treatment
Other	Change in pulmonary function tests at end of treatment, 1 and 2 years	Change from baseline pulmonary function test (DLCO/TLCO percentage of normal) will be compared	3 months & 1 year after end of treatment
Other	Correlation between maximum tumour dimension at baseline and end of treatment with PFS	The relationship between maximum tumour dimension at baseline and at end of treatment and PFS will be examined. This may also be analysed within the groups that achieve/do not achieve CMR after 2 cycles and may also be adjusted for the use of consolidation radiotherapy	Up to 5 years after end of treatment
Primary	Progression free survival (PFS)	Time from randomisation to first date of progression or death	3 years from end of treatment
Secondary	PET-CMR (complete metabolic response) rate	Proportion of patients who have Deauville score 1-3 on PET-CT scan	At the end of cycle 2 (each cycle is 28 days)
Secondary	Event-free survival (EFS)	Time from randomisation to first date of progression, death or a positive PET2 scan (whichever occurs first)	5 years from end of treatment
Secondary	Overall survival (OS)	Time from randomisation to death	5 years from end of treatment
Secondary	Incidence of second cancers and cardiovascular disease	Proportion in each arm who develop a second cancer or cardiovascular disease	5 years from end of treatment
Secondary	Safety and toxicity of ABVD and A2VD as described by CTCAE v5.0	Numbers of patients experiencing a grade 3+ adverse event of each type will be presented and compared between the arms. Only patients who start treatment will be included	From start of treatment to 30 days post treatment