Adcetris (Brentuximab Vedotin), Combination Chemotherapy, and Radiation Therapy in Treating Younger Patients With Stage IIB, IIIB and IV Hodgkin Lymphoma

PRIMARY OBJECTIVES:

- 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).

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

SECONDARY OBJECTIVES:

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

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

- 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.

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

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

OUTLINE:

AEPA REGIMEN: Patients receive brentuximab vedotin on days 1, 8, and 15, etoposide on days 1
to 5, prednisone three times daily (TID) on days 1 to 15, and doxorubicin hydrochloride 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 on days 1 and 8, brentuximab vedotin days 1
and 8, prednisone TID on days 1 to 15, and dacarbazine on days 1 to 3. Treatment repeats
every 21-28 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.

Inclusion Criteria:

- Histologically confirmed, previously untreated CD30+ classical Hodgkin Lymphoma (HL).
(Participants receiving limited emergent radiation therapy (RT) or steroid therapy -
maximum of 7 days - because of cardiopulmonary decompensation or spinal cord
compression will be eligible for protocol enrollment).

- Age ≤ 18 years at the time of enrollment (i.e., participants are eligible until their
19th birthday).

- Ann Arbor stage IIB, IIIB, IVA, or IVB.

- Adequate renal function based on GFR ≥ 70 ml/min/1.73m^2 or serum creatinine adjusted
for age and gender.

- Adequate hepatic function (total bilirubin < 1.5 x ULN for age, and SGOT/SGPT < 2.5 x
ULN for age).

- Female participant who is post-menarchal must have a negative serum pregnancy test.

- Female or male participant of reproductive potential must agree to use an effective
contraceptive method throughout duration of study treatment.

Exclusion Criteria:

- CD30 negative HL.

- Has received prior therapy for Hodgkin lymphoma, except as noted above.

- Inadequate organ function as described above.

- Inability or unwillingness of research participant or legal guardian / representative
to give written informed consent.