Avelumab in the Frontline Treatment of Advanced Classical Hodgkin Lymphoma - a Window Study

Inclusion Criteria:

* Previously untreated classical Hodgkin lymphoma
* High risk stage II (defined as stage IIB, presence of bulky disease, 3 or more sites of disease), stage III or IV as assessed by FDG-PET/CT
* ECOG performance status 0-1
* Adequate bone marrow function (Hb \>80g/l, Platelets \>75 x 10\^9/l, neutrophils \>1.0 x 10\^9/l)
* Adequate liver function tests (ALT/AST \<2.5 x ULN, total serum bilirubin level \<1.5 x ULN)
* Creatinine clearance \>50ml/min calculated by Cockroft-Gault formula
* Written informed consent
* Willing to comply with the contraceptive requirements of the trial
* Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

Exclusion Criteria:

* Nodular lymphocyte predominant Hodgkin lymphoma
* Compressive symptoms due to disease (which may or may not be bulky). If there is evidence of compression of vital structures radiologically but the patient is asymptomatic, the case must be discussed with the TMG.
* Requirement for urgent treatment due to life-threatening complications of the disease
* Women who are pregnant or breastfeeding
* History of colitis, inflammatory bowel disease or pneumonitis
* Patients with autoimmune disorders excluding patients with vitiligo, diabetes mellitus type 1, hypo- and hyperthyroidism, coeliac disease not requiring immunosuppressive therapy
* Immunosuppressive therapy within the last 2 months, apart from inhaled, intranasal, topical corticosteroids or systemic corticosteroids at low doses (≤10mg prednisolone per day or equivalent - see steroid exception below)
* Prior history of solid organ or allogeneic haematopoietic stem cell transplant
* Positive serology for hepatitis B or C (unless due to vaccination), or hepatitis C RNA negative if hepatitis C antibody positive
* Known HIV infection
* Administration of a live vaccine within 30 days prior to study entry
* History of allergy to monoclonal antibodies, anaphylaxis or uncontrolled allergy
* Chemo- or radiotherapy within 15 days prior to registration. Corticosteroids permitted for disease control but must be weaned down to ≤10mg prednisolone per day or equivalent at least 7 days prior to starting avelumab - steroids may only be started for disease control after the baseline PET-CT
* Persisting toxicity (of \>grade 1) related to prior therapy, however, alopecia, sensory neuropathy Grade \<2, or other grade \<2 not constituting a safety risk based on investigator's judgement are acceptable
* Major surgery within 4 weeks prior to registration
* Active infection requiring systemic therapy
* Myocardial infarction, unstable angina, coronary artery bypass graft, cerebrovascular accident or transient ischaemic attack within the past 6 months
* Non-haematological malignancy within the past 3 years (some exceptions apply)
* Previously treated haematological malignancy
* Any uncontrolled medical condition which can impair delivery of planned immunochemotherapy
* Patient not deemed suitable for ABVD/AVD/escalated-BEACOPP/BEACOPP-14