Pediatric Classical Hodgkin Lymphoma Consortium Study: cHOD17

PRIMARY OBJECTIVES

- To evaluate the efficacy (adequate response) after 2 cycles of BEABOVP (bendamustine
substitution for mechlorethamine in the original Stanford V chemotherapy backbone) in
low-risk and intermediate-risk patients with classical Hodgkin lymphoma (cHL).

- To estimate the event-free survival in high-risk patients with classical Hodgkin
lymphoma (cHL).

SECONDARY OBJECTIVES

- To describe the acute hematologic and infectious toxicities of BEABOVP (bendamustine
substitution for mechlorethamine in the original Stanford V chemotherapy backbone) in
patients with low-risk and intermediate- risk cHL as they relate to transfusion
requirements, hematopoietic growth factor support, episodes of febrile neutropenia and
hospitalizations, according to the NCI Common Terminology Criteria for Adverse Events
(CTCAE), version 5.0.

- To describe the acute hematologic, neuropathic, and infectious toxicities of AEPA/CAPDac
in patients with high-risk cHL as they relate to transfusion requirements, hematopoietic
growth factor support, episodes of grade 3 and 4 sensory or motor neuropathy, episodes
of febrile neutropenia and hospitalizations, according to the NCI Common Terminology
Criteria for Adverse Events (CTCAE), version 5.0.

- To evaluate patterns of failure in irradiated and non-irradiated patients.

- To estimate the EFS functions of LR and IR patients, and compare with those in
previously published studies.

- To estimate the response rate in HR patients and compare with historical and literature
rates.

- To compare response rates in LR and IR patients with historical and literature rates.

- To compare the EFS function of HR patients with that in previously published studies.

EXPLORATORY OBJECTIVES

- To evaluate the plasma pharmacokinetics of bendamustine along with predictors of its
variability when used as part of BEABOVP regimen for pediatric cHL patients.

- To explore the patterns and dynamics of T-cell clonality in classical Hodgkin lymphoma.

- To explore the association between TARC, total metabolic tumor volume, stage, risk group
and treatment response.

- To obtain baseline testing by St. Jude Lifetime Study (SJLIFE) to allow for enhanced
survivorship follow-up

Low-risk and Intermediate-risk: Low-risk patients will receive 2 cycles of BEABOVP and
Intermediate-risk patients will receive 3 cycles of BEABOVP.

BEABOVP regimen: Patients will receive bendamustine day 1, etoposide day 15, Adriamycin®
(doxorubicin) days 1 and 15, bleomycin days 8 and 22, Oncovin® (vincristine) days 8 and 22,
vinblastine days 1 and 15, and prednisone two or three times daily every other day for 14
days of each cycle.

High-risk patients will receive 2 cycles of AEPA and 4 cycles of CAPDac.

AEPA regimen: Patients will receive Adcedris® (brentuximab vedotin) days 1, 8 and 15,
etoposide days 1 to 5, prednisone two or three times daily days 1 to 15 and Adriamycin®
(doxorubicin) days 1 and 15.

CAPDac regimen: Patients will receive cyclophosphamide days 1 and 8, Adcetris® (brentuximab
vedotin) days 1 and 8, prednisone two or three times daily days 1 to 15 and Dacarbazine®
(DTIC) days 1 to 3.

Residual node radiotherapy will be given at the end of all chemotherapy only to involved
nodes that do not have an AR after 2 cycles of therapy for all risk groups.

Steroids will be omitted after 2 cycles for any IR or HR patient with an AR after 2 cycles of
therapy.

Inclusion Criteria:

- Histologically confirmed, previously untreated CD30+ classical HL. (Participants are
still eligible if they received limited emergent RT or steroid therapy - maximum of 7
days if within the last month or as approved by PI).

- Age ≤ 21 years at the time of diagnosis (i.e., participants are eligible until their
22nd birthday) for low-risk and intermediate-risk

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

- All Ann Arbor stages.

- Low-Risk: IA, IIA (excluding patients with "E" lesions or mediastinal bulk)

- Intermediate-Risk: IA or IIA with "E" lesions or bulky mediastinal adenopathy
(mediastinal mass to thoracic cavity ratio 33% or greater by chest radiograph)
and IB, IIIA.

- High-Risk: IIB, IIIB, IV

- Adequate renal function based on GFR ≥ 70 ml/min/1.73m2 OR serum creatinine adjusted
for age and gender as follows: Age 1 to < 2 years: maximum serum creatinine 0.6 mg/dL
for males and 0.6 mg/dL for females, Age 2 to < 6 years: maximum serum creatinine 0.8
mg/dL for males and 0.8 mg/dL for females, Age 6 to < 10 years: maximum serum
creatinine 1 mg/dL for males and 1 mg/dL for females, Age 10 to < 13 years: maximum
serum creatinine 1.2 mg/dL for males and 1.2 mg/dL for females, Age 13 to < 16 years:
maximum serum creatinine 1.5 mg/dL for males and 1.4 mg/dL for females, Age ≥16 years:
maximum serum creatinine 1.7 mg/dL for males and 1.4 mg/dL for females

- Adequate hepatic function (total bilirubin ≤ 1.5 x ULN for age, and AST/ALT ≤ 2.5 x
ULN for age).

- Adequate hematologic criteria at baseline, unless secondary to Hodgkin disease
diagnosis

- Absolute neutrophil count (ANC) ≥1000/µL

- Platelets ≥ 75,000/µL

- Adequate cardiac function defined as shortening fraction of ≥ 27% by echocardiogram,
unless decreased function is due to large mediastinal mass or effusion related to HL.

- Adequate pulmonary function defined as no evidence of dyspnea at rest, no exercise
intolerance, and a pulse oximetry > 92% on room air unless secondary to a large
mediastinal mass or effusion related to HL.

- Female participant who is post-menarchal must have a negative urine or 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

- Inadequate organ function

- High-risk participants with a history of ≥ grade 2 peripheral neuropathy or any active
neurologic disease, that in the opinion of the treating investigator, would impede
ability to assess neurologic toxicities.

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