AHOD1331, A Randomized Phase III Study of Brentuximab Vedotin (SGN-35, IND #117117) for Newly Diagnosed High-Risk Classical Hodgkin Lymphoma (cHL) in Children and Adolescents
1.1.1 To assess the event free survival (EFS) of a novel regimen incorporating brentuximab vedotin (Bv; AdcetrisTM) in the chemotherapy backbone of doxorubicin (Adriamycin), vincristine, etoposide, prednisone and cyclophosphamide (Bv-AVEPC) in newly diagnosed high-risk cHL compared to those treated with ABVE-PC.
1.2.1 To determine whether children/adolescents with high-risk cHL treated with Bv-AVEPC have a higher rate of early response (determined by FDG-PET) and a reduction in response-directed radiation therapy (RT) compared to those treated with ABVE-PC.
1.2.2 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).
Childhood International Prognostic Score (CHIPS)
1.3.1 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.
1.3.2 To determine the incidence of preferentially expressed antigen in melanoma (PRAME) and testis-specific antigens in EBV- cHL tumors and the incidence of EBV antigens (EBNA1, LMP1, LMP2) in EBV+ cHL tumors, with the goal of developing strategies to integrate cellular therapy into treatment for newly diagnosed high-risk cHL.
1.3.3 To incorporate qualitative visual FDG-PET into response-directed treatment algorithms and explore quantitative FDG-PET and CT definitions of tumor burden and response for incorporation into next generation pediatric cHL risk-stratification schemes.
1.3.4 To evaluate the reduction in normal tissue irradiation associated with the current treatment approach compared to the volume of historic IFRT fields.
1.3.5 To evaluate EFS and patterns of relapse following protocol-specified RT utilization and treatment volumes.
Patient Reported Outcomes (PRO) of Peripheral Neuropathy and Health-Related Quality of Life
1.3.6 To characterize the extent of chemotherapy induced peripheral neuropathy (CIPN), as reported by patients and parent proxies, through serial administration of the FACT-GOG-NTX.
1.3.7 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 CHRIs-Global scale (e.g., physical health, pain, emotional functioning).
1.3.8 To perform a cross validation of the FACT-GOG-NTX with the 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 (See Appendix VII).
Economic (For US Institutions Only)
1.3.9 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 adolescents (See Appendix VIII).