This study aims to evaluate the efficacy brentuximab vedotin as consolidation treatment in patients with stage I/II Hodgkin's lymphoma and 18-fluorodeoxyglucose (FDG) -PET positivity after 2 cycles of ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine).

This study aims to evaluate the progression free survival after treatment for patient with stage I/II supradiaphragmatic HL patient and PET positive after 2 courses of ABVD.

The treatment consist of 3 phases :

• induction treatment with 2 cycles every 3 weeks of bleomycin, etoposide, Adriamycin, cyclophosphamide, oncovin, procarbazine, and prednisone (BEACOPP) escalated
• radiotherapy 30 Gy starting 3 to 4 weeks after last day of second course of BEACOPP-escalated
• consolidation treatment with 8 cycles every 21 days of brentuximab vedotin

Inclusion Criteria:

1. Patients must have histologically confirmed cluster of differentiation antigen 30+ (CD30+) classical Hodgkin lymphoma

2. Patients must have provided voluntary written informed consent

3. Supradiaphragmatic Ann Arbor clinical stage I or II

4. Mandatory PET scan performed at diagnosis

5. Patients treated with first-line ABVD and PET scan positive after 2 cycles (Deauville score 4 & 5)

6. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

7. Life expectancy > 6 months

8. Patients must be 18-65 years of age

9. Patients must be available for periodic blood sampling, study-related assessments and management of toxicity at the treating institution

10. Female patients who:

    • Are postmenopausal for at least 1 year before the screening visit OR are surgically sterile OR
    • If they are of childbearing potential, agree to practice 2 effective methods of contraception at the same time

11. Male patients, even if surgically sterilized, who agree to practice effective barrier contraception during the entire study treatment period and through 6 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse

12. Clinical laboratory values as specified below before the first dose of study drug:

    • Absolute neutrophil count ≥ 1,500/µL
    • Platelet count ≥ 75,000/ µL
    • Total bilirubin must be < 1.5 x the upper limit of the normal (ULN) unless the elevation is known to be due to Gilbert syndrome
    • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST)must be < 3 x the upper limit of the normal range
    • Serum creatinine must be < 2.0 mg/dL and/or creatinine clearance or calculated creatinine clearance > 40 mL/minute
    • Hemoglobin must be ≥ 8g/dL

13. Patient affiliated to social security system

Exclusion Criteria:

1. Patients with dementia or altered mental status that would preclude compliance with drug delivery

2. Women who are pregnant or breastfeeding

3. Patients with symptomatic pulmonary disease

4. Patients with known history of any of the following cardiovascular conditions:

   • Myocardial infarction within 2 years of inclusion
   • 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
   • Recent evidence (within 6 months before first dose of study drug) of a left-ventricular ejection fraction <50%

5. Any history of cancer or cancer treatment during the last 3 years with the exception of non-melanoma skin cancer or stage 0 (in situ) carcinoma of any type if they have undergone complete resection

6. Uncontrolled infectious disease, including active Hepatitis B Virus (HBV) infection defined by either detection of Hepatitis B surface (HBs) Antigen or presence of Hepatitis B core (HBc) antibody without detectable anti HBs antibody

7. Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics at the time of inclusion and planned to be still on going within 2 weeks prior to first study drug dose

8. Known Human Immunodeficiency Virus (HIV), known or suspected hepatitis C Virus (HCV) or human T-cell lymphotrophic virus (HTLV) serology positivity

9. Patients who have been treated previously with any anti-CD30 antibody

10. Known hypersensitivity to any excipients contained in the brentuximab vedotin formulation

11. Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of Progressive Multifocal Leukoencephalopathy (PML)

12. Any sensory or motor peripheral neuropathy greater than or equal to Grade 2

13. Patients that have not completed any prior treatment chemotherapy and/or other investigational agents within at least 5 half-lives of last dose of that prior treatment