brentuximab vedotin associated with chemotherapy in untreated patients with hodgkin lymphoma.

Conditions: Hodgkin Lymphoma

Summary: this study aims to evaluate the efficacy of brentuximab vedotin + avd combination (doxorubicine, vinblastine, dacarbazine) in patients with hodgkin lymphoma stage i / ii with an unfavorable diagnosis, assessed by the negativity of pet (positron emission tomography ) after two cycles of chemotherapy.

patients will receive either abvd chemotherapy (standard treatment = doxorubicin, bleomycin, vinblastine, dacarbazine) or the brentuximab vedotin in combination with chemotherapy avd (study treatment), depending on randomization. radiotherapy is planned after chemotherapy or immunochemotherapy. pet scans will be performed before inclusion, after 2 cycles of chemotherapy and after 4 cycles of chemotherapy (if pet after two cycles was positive), at the end of treatment and during follow-up period.

Eligibility criteria:
inclusion criteria: * histologically confirmed cd30+ classical hodgkin lymphoma * supradiaphragmatic ann arbor clinical stage i or ii * previously untreated * pet scan without iv contrast at diagnosis available for central review with at least one hypermetabolic lesion * unfavourable (u) characteristics according to the classic eortc/lysa clinical prognostic factors, including patients with at least one of the following factors: * csii ≥ 4 nodal areas * age ≥ 50 yrs * m/t ratio ≥ 0.35 * esr ≥ 50 (without b-symptoms) or esr ≥ 30 with b-symptoms * ecog performance status 0-2 * life expectancy \> 6 months * age 18 to 60 years * availability 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, through 6 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse * male patients, even if surgically sterilized (ie, status postvasectomy), who: o 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. * written informed consent. * required baseline laboratory data: * absolute neutrophil count ≥ 1,500/µl * platelet count ≥ 75,000/ µl * hemoglobin ≥ 8g/dl * serum total bilirubin ≤ 1.5 x uln unless the elevation is known to be due to gilbert syndrome. * serum creatinine ≤ 2.0 mg/dl and/or calculated creatinine clearance \> 40 ml/minute (cockcroft-gault formula or mdrd) * alanine aminotransferase (alt) and aspartate aminotransferase (ast) ≤ 3 x uln exclusion criteria: * histological diagnosis different from classical hodgkin lymphoma. nodular lymphocyte predominant subtypes (nodular paragranuloma or poppema paragranuloma) are excluded. * known cerebral or meningeal disease of any etiology, including signs or symptoms of pml * any sensory or motor peripheral neuropathy ≥ grade 2 * known history of any of the following cardiovascular conditions * myocardial infarction within 2 years of randomization * new york heart association (nyha) class iii or iv heart failure (see appendix 14) * 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 30 days before first dose of study drug) of a left-ventricular ejection fraction \<50% * unstable diabetes mellitus (to avoid uninterpretable fdg-pet scan). * known hiv positive * hcv positive * hbv positive. this means: * hbsag positive * hbsag negative, anti-hbs positive and/or anti-hbc positive and detectable viral dna (hbsag negative patients and viral dna negative and patients seropositive due to a history of hepatitis b vaccine are eligible). * any history of cancer during the last 5 years, with the exception of non-melanoma skin tumors. carcinoma in situ of any type not excluded if complete resection. * dementia or altered mental status * pregnancy or breastfeeding. * previous treatment with any anti-cd30 antibody. * known hypersensitivity to any excipients contained in the bv formulation or known contra-indication to any drug contained in the chemotherapy regimens * treatment with corticosteroids before baseline pet scan * known active viral, bacterial, or fungal infection requiring treatment with antimicrobial therapy or with untreated known active grade 3 viral, bacterial, or fungal infection, within 2 weeks prior to the first dose of bv * treatment with any investigational drug within 30 days before first cycle of treatment

Keywords: hl