Brentuximab Vedotin in Early Stage Hodgkin Lymphoma

Eligibility 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
• * 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