Very Early PET-response Adapted Targeted Therapy for Advanced Hodgkin Lymphoma: a Single -Arm Phase II Study

Inclusion Criteria:

* Previously untreated, histologically proven classical Hodgkin lymphoma;
* Staged by PET with diagnostic-quality CT (i.v. contrast).
* Clinical stages according to Lugano 2014 and based on FDG/PET CT:

  * Stage IIB with large mediastinal mass \> 1/3 max transverse diameter thorax and/or extranodal lesion(s)
  * Stage III - IV
* Consent to participation in translational research:
* Archival tumor tissue available (15 blank formalin fixed paraffin embedded tissue samples mounted on APES slides or a tissue block).
* Women of child bearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours prior to the first dose of study treatment.
* Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 6 months after the last dose of treatment. A highly effective method of birth control is defined as a method which results in a low failure rate (i.e. less than 1 percent per year) when used consistently and correctly.
* Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 6 months after the last study treatment.
* Absence of any medical, psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
* Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations.

Exclusion Criteria:

* Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of Progressive Multifocal Leukoencenphalopathy
* Symptomatic neurologic disease compromising normal activities of daily living or requiring medications
* Sensory or motor peripheral neuropathy greater than or equal to grade 2 according to CTCAE version 4.0
* Any of the following cardiovascular conditions or values:

within 6 months before registration:

* A left-ventricular ejection fraction \<50 percent (at registration)
* New York Heart Association (NYHA) Class III or IV heart failure.
* Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
* symptomatic coronary heart disease (stable angina pectoris is allowed)
* severe uncontrolled hypertension within 2 years before registration
* Myocardial infarction
* Patients with poorly controlled diabetes mellitus (HbA1c \> 7.5 percent or a fasting blood sugar \> 200 mg/dL).
* Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks prior to registration.
* Known HIV infection, chronic active hepatitis C, HBV positivity (HBsAg + patients; HBsAg -/HBcAb+/HBV DNA+ patients).

Note: HBsAg-/HBV DNA - patients are eligible; patients who are seropositive due to vaccination are eligible

* Concomitant or previous malignancies within the past 5 years with the exception of adequately treated carcinoma in situ of the cervix , nonmelanoma skin cancer.
* Previous treatment with anti CD30 antibodies
* Known hypersensitivity to any excipient contained in Brentuximab Vedotin formulation and other study drugs. Refer to Summary Product Characteristics for list of excipients.
* Concurrent anti-cancer treatment or use of any investigational agent(s)