Brentuximab Vedotin, Combination Chemotherapy, and Radiation Therapy in Treating Younger Patients with Stage IIB or IIIB-IVB Hodgkin Lymphoma

PRIMARY OBJECTIVES:

I. To evaluate the safety of brentuximab vedotin, etoposide, prednisone and doxorubicin hydrochloride (AEPA)/cyclophosphamide, brentuximab vedotin, prednisone and dacarbazine (CAPDAC), as well as the efficacy (early complete response) after 2 cycles of AEPA chemotherapy in high risk patients with Hodgkin lymphoma (HL).

II. To compare the event-free survival in high risk HL patients treated with AEPA/CAPDac to the historical control HOD99 unfavorable risk 2 arm (UR2).

SECONDARY OBJECTIVES:

I. To estimate the number of patients with adequate response according to the definitions in the European-Network (Euro-Net) C1 after 2 cycles of AEPA.

II. To evaluate the safety of Adcetris (brentuximab vedotin) in the AEPA/CAPDac regimen in children with high risk HL.

III. To describe acute hematologic, neuropathic, and infectious toxicities as they relate to transfusion requirements, growth factor support, episodes of febrile neutropenia and hospitalizations, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.

IV. To study the association between local failure and original lymph node region and volume of radiation (patterns of treatment failure).

V. To assess patient-reported symptoms and health-related quality of life in children with high risk HL compared to those treated on the unfavorable HOD99 treatment arm.

EXPLORATORY OBJECTIVES:

I. To compare the ratings of neuropathic toxicity according to the NCI Common Terminology Criteria for Adverse Events, version 4.0 to the Pain Quality Assessment Scale (PQAS).

II. To describe the pharmacokinetics of Adcetris when used as part of AEPA/CAPDac for pediatric HL patients. (Completed as of 09-11-2014)

III. To describe the immunogenicity of Adcetris and the relationship between early response and presence of anti-chimeric anti-body.

IV. To explore the association between cluster of differentiation (CD)30 density in Reed Sternberg cells in paraffin embedded tumor tissue and early response and event-free survival.

V. To explore the association between soluble CD30 (in serum/plasma) and early response, event-free survival.

VI. To identify pharmacogenetic predictors for treatment-related outcomes in the context of AEPA/CAPDac.

VII. Compare dosimetrically, the ability of proton-based radiation therapy (PBRT) to spare adjacent normal tissues compared to photon-based radiation therapy.

OUTLINE:

AEPA REGIMEN: Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on days 1, 8, and 15, etoposide IV over 1-2 hours on days 1-5, prednisone orally (PO) three times daily (TID) on days 1-15, and doxorubicin hydrochloride IV over 1-6 hours on days 1 and 15. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.

CAPDac REGIMEN: Patients receive cyclophosphamide IV over 60 minutes on days 1 and 8, brentuximab vedotin IV over 30 minutes on days 1 and 8, prednisone PO TID on days 1-15, and dacarbazine IV over 15-30 minutes on days 1-3. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Beginning 2-3 weeks after CAPDac chemotherapy, patients with lymph nodes that do not go into remission after 2 courses of AEPA chemotherapy undergo radiation therapy daily, 5 days a week for 3-4 weeks.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 2 years, every 6 months for 2 years, and then annually for 5 years.