PRIMARY OBJECTIVE:

      I. To assess the event free survival (EFS) of a novel regimen incorporating brentuximab
      vedotin (Bv; Adcetris) in the chemotherapy backbone of doxorubicin hydrochloride
      (doxorubicin) (Adriamycin), vincristine sulfate (vincristine), etoposide, prednisone and
      cyclophosphamide (Bv-AVEPC) in newly diagnosed high-risk classical Hodgkin lymphoma (cHL)
      compared to those treated with Adriamycin, bleomycin sulfate, vincristine sulfate, etoposide,
      prednisone, and cyclophosphamide (ABVE-PC).

      SECONDARY OBJECTIVES:

      I. To determine whether children/young adults with high-risk cHL treated with Bv-AVEPC have a
      higher rate of early response (determined by fludeoxyglucose F 18 [FDG]-positron emission
      tomography [PET]) and a reduction in protocol directed radiation therapy (RT) compared to
      those treated with ABVE-PC.

      II. To compare the rate of neuropathy (>= grade 3) among patients treated on the Bv-AVEPC
      (experimental arm) to patients treated on the ABVE-PC (standard arm).

      EXPLORATORY OBJECTIVES:

      I. To validate and compare the Childhood Hodgkin International Prognostic Score (CHIPS) to
      conventional Ann Arbor stage (stages II B with bulk, III B, IV A or B) in predicting outcome
      in high-risk childhood cHL.

      II. To determine the incidence of preferentially expressed antigen in melanoma (PRAME) and
      testis-specific antigens in Epstein-Barr virus (EBV)- cHL tumors and the incidence of EBV
      antigens (Epstein-Barr nuclear antigen 1 [EBNA1], Epstein-Barr virus latent membrane protein
      1 [LMP1], large multifunctional peptidase 2 [LMP2]) in EBV+ cHL tumors, with the goal of
      developing strategies to integrate cellular therapy into treatment for newly diagnosed
      high-risk cHL. (Biology) III. To incorporate qualitative visual FDG-PET into
      response-directed treatment algorithms and explore quantitative FDG-PET and computed
      tomography (CT) definitions of tumor burden and response for incorporation into next
      generation pediatric cHL risk-stratification schemes, exploring the extension of these
      algorithms to young adults. (Imaging) IV. To evaluate the reduction in normal tissue
      irradiation associated with the current treatment approach compared to the volume of historic
      involved field radiation therapy (IFRT) fields. (Radiation Therapy) V. To evaluate EFS and
      patterns of relapse following protocol-specified RT utilization and treatment volumes.
      (Radiation Therapy) VI. To characterize the extent of chemotherapy induced peripheral
      neuropathy (CIPN), as reported by patients and parent proxies, through serial administration
      of the Functional Assessment of Cancer Therapy-Gynecologic Oncology Group-Neurotoxicity
      (FACT-GOG-NTX). (Patient Reported Outcomes [PRO] of Peripheral Neuropathy and Health-Related
      Quality of Life) VII. To describe the Health-Related Quality of Life (HRQL) consequences of
      peripheral neuropathy over time by correlating total neuropathy scale scores with the
      individual items with the Child Health Ratings Inventories (CHRIs)-Global scale (e.g.,
      physical health, pain, emotional functioning). (PRO of Peripheral Neuropathy and
      Health-Related Quality of Life) VIII. To perform a cross validation of the FACT-GOG-NTX with
      the Total Neuropathy Score-Pediatric Vincristine (TNS-PV) to determine the performance of
      both measures with the use of brentuximab vedotin in a limited institutional approach in
      children and adolescents with cHL. (PRO of Peripheral Neuropathy and Health-Related Quality
      of Life) IX. To assess the resource use and cost implications of Bv in combination with
      chemotherapy and radiotherapy (RT) for newly diagnosed high-risk cHL in children and young
      adults. (Economic) X. To estimate the risk of relapse among rapidly responding lesions (RRL)
      subjects that have at least one lesion that is Deauville 3 at PET 2. (Follow-up of Deauville
      score 3 lesions on FDG-PET imaging [confirmed by central imaging review]) XI. To characterize
      the pharmacokinetics of brentuximab vedotin in children < 13 years of age.

      OUTLINE: Patients are randomized to 1 of 2 treatment arms.

      ARM I (ABVE-PC): Patients receive doxorubicin hydrochloride intravenously (IV) over 1-15
      minutes on days 1-2, bleomycin sulfate IV over 10 minutes or subcutaneously (SC) on days 1
      and 8, vincristine sulfate IV over 1 minute on days 1 and 8, etoposide IV over 60-120 minutes
      on days 1-3, prednisone orally (PO) twice daily (BID) or methylprednisolone IV on days 1-7,
      and cyclophosphamide IV over 30-60 minutes on days 1 and 2.

      ARM II (Bv-AVEPC): Patients receive brentuximab vedotin IV over 30 minutes on day 1. Patients
      also receive doxorubicin hydrochloride, etoposide, prednisone or methylprednisolone, and
      cyclophosphamide as in Arm I and vincristine sulfate IV over 1 minute on day 8.

      In both arms, treatment repeats every 21 days for 5 cycles in the absence of disease
      progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 3, 6, 9, 12, 18, 24, 30, 36,
      and 48 months.