Brentuximab Vedotin in Early Stage Hodgkin Lymphoma

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 (definedas greater than a third of the transthoracic diameter at any level of thoracicvertebra as determined by CT) or B symptoms. Bulky disease at other sites isacceptable. Extranodal disease (single extranodal site (stage I) or contiguous nodalextension (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 ofischaemic heart disease or hypertension should have a left ventricular ejectionfraction of ≥50%)

• Creatinine clearance (measured or calculated >40ml/min

• Total bilirubin <1.5 x upper limit of normal, unless attributable to disease orknown 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, includingcontraceptive advice, where applicable

• Written informed consent

Exclusion Criteria:

• Previous treatment for Hodgkin lymphoma, excluding short courses of oralcorticosteroids 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 excisedcarcinoma in situ of any type and basal or squamous cell carcinoma of the skin arenot excluded

• Recurrent or persistent other cancer within last 5 years irrespective of date ofinitial diagnosis

• Pre-existing grade ≥1 sensory or motor neuropathy from any cause

• History of or current progressive multi-focal leukoencephalopathy or other chroniccondition of the brain

• Symptomatic neurologic disease compromising normal activities of daily living orrequiring medications

• Infection with HIV, hepatitis C or active hepatitis B infection (surface antigen orDNA positive)

• Any active systemic viral, bacterial or fungal infection requiring systemicantibiotics, antivirals or antifungals within 2 weeks prior to first trial drug dose

• Receiving or recently treated with any other investigational agent (within 4 weeksof trial entry)

• Pregnant or breastfeeding women

• Known hypersensitivity to recombinant proteins, murine proteins, or to any excipientcontained in the drug formulation of brentuximab vedotin or any component of ABVD

• Known history of any cardiovascular or respiratory conditions that would precludeanthracycline or bleomycin administration

• Other significant medical or psychiatric comorbidity that in the opinion of theinvestigator would make administration of ABVD or A2VD hazardous