Brentuximab Vedotin as Consolidation Treatment in Patients With Stage I/II HL and PET Positivity After 2 Cycles of ABVD

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

• Patients must have histologically confirmed cluster of differentiation antigen 30+ (CD30+) classical Hodgkin lymphoma
• Patients must have provided voluntary written informed consent
• Supradiaphragmatic Ann Arbor clinical stage I or II
• Mandatory PET scan performed at diagnosis
• Patients treated with first-line ABVD and PET scan positive after 2 cycles (Deauville score 4 & 5)
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Life expectancy > 6 months
• Patients must be 18-65 years of age
• Patients must be available for periodic blood sampling, study-related assessments and management of toxicity at the treating institution
• 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
• 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
• 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
• Patient affiliated to social security system

Exclusion criteria

• Patients with dementia or altered mental status that would preclude compliance with drug delivery
• Women who are pregnant or breastfeeding
• Patients with symptomatic pulmonary disease
• 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%
• 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
• 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
• 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
• Known Human Immunodeficiency Virus (HIV), known or suspected hepatitis C Virus (HCV) or human T-cell lymphotrophic virus (HTLV) serology positivity
• Patients who have been treated previously with any anti-CD30 antibody
• Known hypersensitivity to any excipients contained in the brentuximab vedotin formulation
• Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of Progressive Multifocal Leukoencephalopathy (PML)
• Any sensory or motor peripheral neuropathy greater than or equal to Grade 2
• 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