Brentuximab Vedotin in Early Stage Hodgkin Lymphoma

Официальное название

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

Обзор

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.

Подробное описание

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of their randomised chemotherapy followed by involved site radiotherapy * Patients with Deauville score 5 will be withdrawn from trial treatment.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

Вмешательства

• Лучевая терапия Involved site radiotherapy
  Involved site radiotherapy as per International Lymphoma Radiation Oncology Group (ILROG) guidelines. Recommended dose 30Gy
• Препарат Doxorubicin
  See arm description
• Препарат Bleomycin
  See arm description
• Препарат Brentuximab vedotin
  See arm description
• Препарат Vinblastine
  See arm description
• Препарат Dacarbazine
  See arm description
• Препарат Haematopoietic growth factor
  See arm description

Первичные конечные точки

• Progression free survival (PFS) [Срок оценки: 3 years from end of treatment]

Вторичные конечные точки (5)

• PET-CMR (complete metabolic response) rate [Срок оценки: At the end of cycle 2 (each cycle is 28 days)]
• Event-free survival (EFS) [Срок оценки: 5 years from end of treatment]
• Overall survival (OS) [Срок оценки: 5 years from end of treatment]
• Incidence of second cancers and cardiovascular disease [Срок оценки: 5 years from end of treatment]
• Safety and toxicity of ABVD and A2VD as described by CTCAE v5.0 [Срок оценки: From start of treatment to 30 days post treatment]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Великобритания · 31 центр

• Hampshire Hospitals NHS Foundation Trust — Basingstoke
• Blackpool Victoria Hospital — Blackpool
• Freeman Hospital, Newcastle — Newcastle upon Tyne
• Lanarkshire — Glasgow
• St George's Hospital — London
• Aberdeen Royal Infirmary — Aberdeen
• University Hospitals Birmingham — Birmingham
• Glan Clwyd Hospital — Bodelwyddan
• … и ещё 23 центра

Австралия · 10 центров

• Royal North Shore Hospital — Saint Leonards
• Townsville University Hospital — Townsville
• Royal Adelaide Hospital — Adelaide
• Box Hill Hospital — Box Hill
• Royal Brisbane and Women's Hospital — Brisbane
• Royal Darwin Hospital — Darwin
• Liverpool Hospital — Liverpool
• Sunshine Hospital (Western Health) — Melbourne
• … и ещё 2 центра

Канада · 7 центров

• QEII Health Sciences Centre — Halifax
• Juravinski Cancer Centre — Hamilton
• Ottowa Hospital Research Institute — Ottawa
• Saint John Regional Hospital — Saint John
• University Health Network Princess Margaret Cancer Centre — Toronto
• Vancouver Cancer Centre — Vancouver
• CancerCare Manitoba — Winnipeg

Бельгия · 5 центров

• AZ Delta Campus Rumbeke — Roeselare
• Universitair Ziekenhuis Antwerpen — Antwerp
• Ziekenhuis Netwerk Antwerpen — Antwerp
• UZ Leuven — Leuven
• CHU-UCL Namur — Namur

Нидерланды · 5 центров

• Amsterdam UMC - location VUMC — Amsterdam
• Reinier de Graafweg 3-11 - Postbus 5011 - 2625 AD Delft — Delft
• Universitair Medisch Centrum Groningen — Groningen
• Radboud University Medical Center Nijmegen — Nijmegen
• NL 331 - Haaglanden Medisch Centrum (HMC) - Haaglanden MC — The Hague

США · 3 центра

• Stanford University - (Stanford Cancer Institute) — Stanford
• University of Miami School of Medicine — Miami
• Memorial Sloan Kettering Cancer Center — New York

Ирландия · 3 центра

• St James's Hospital — Dublin
• St. Vincent's University Hospital — Dublin
• University Hospital Galway — Galway

Испания · 3 центра

• Hospital Del Mar — Barcelona
• Institut Catala d'Oncologia — Barcelona
• Complejo Hospitalario de Navarra — Pamplona

Дания · 2 центра

• Aarhus University Hospitak Skjeby — Aarhus
• Rigshospitalet — Copenhagen

Новая Зеландия · 1 центр

• Auckland City Hospital — Auckland

Португалия · 1 центр

• Instituto Portugues de Oncologia de Lisboa Francisco Gentil — Lisbon

Словакия · 1 центр

• Narodny Onkologicky Ustav — Bratislava

Публикации

• 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

Идентификаторы

NCT: NCT04685616 · RADAR · 2020-005160-65 · IISR X25041 · UCL/15/0105 · CCTG HD.12 · IRB number 20230081

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗