Trial Outcomes & Findings for Adcetris (Brentuximab Vedotin), Combination Chemotherapy, and Radiation Therapy in Treating Younger Patients With Stage IIB, IIIB and IV Hodgkin Lymphoma (NCT NCT01920932)

NCT ID: NCT01920932

Last Updated: 2025-12-03

Results Overview

To determine the efficacy of 2 cycles of AEPA chemotherapy, the response rate for the first 32 evaluable participants enrolled was evaluated. If it shown efficacy (detect 20% increase complete rate with 80% power and 5% type I error compared with the proportion of historical control of HOD99 (NCT00145600) unfavorable risk patients had complete rate at week 8 of 17% (24/141), the response results will be reported in a national/international meeting and the study will continue to enroll for a total of 77 patients.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE2
• Target enrollment: 77 participants
• Primary outcome timeframe: After the first 2 cycles of chemotherapy (at approximately 2 months after enrollment)
• Results posted on: 2025-12-03

Participant Flow

Participants were enrolled at 5 institutions between August 2013 to July 2018.

All the 77 patients are eligible for the study. Two out of 77 enrolled patients did not complete the study. One patient died during therapy, and 1 patient withdrew from the study. But both patients are evaluable for the primary objective.

Participant milestones

Measure	AEPA/CAPDac Ann Arbor stage IIB, IIIB, IVA, or IVB participants receive: 2 cycles of AEPA chemotherapy: (A) Brentuximab vedotin 1.2 mg/kg IV (intravenous) days 1, 8 and 15, (E) Etoposide 125 mg/m\^2 IV days 1-5, (P) Prednisone 60 mg/m\^2/day PO (orally) days 1-15, (A) Doxorubicin 40 mg/m\^2 IV days 1 and 15), Followed by 4 cycles of CAPDac: (C) Cyclophosphamide 500 mg/m\^2 IV days 1 and 8, (A) Brentuximab vedotin 1.2 mg/kg IV days 1 and 8, (P) Prednisone 40 mg/m\^2/day PO days 1-15, (Dac) Dacarbazine 250 mg/m\^2 IV days 1-3.). Filgrastim 5 mcg/kg subcutaneous (SC) as clinically indicated. For those with lymph nodes that do not go into remission after 2 courses of AEPA chemotherapy, radiation therapy is given.
Overall Study STARTED	77
Overall Study COMPLETED	75
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Measure	AEPA/CAPDac Ann Arbor stage IIB, IIIB, IVA, or IVB participants receive: 2 cycles of AEPA chemotherapy: (A) Brentuximab vedotin 1.2 mg/kg IV (intravenous) days 1, 8 and 15, (E) Etoposide 125 mg/m\^2 IV days 1-5, (P) Prednisone 60 mg/m\^2/day PO (orally) days 1-15, (A) Doxorubicin 40 mg/m\^2 IV days 1 and 15), Followed by 4 cycles of CAPDac: (C) Cyclophosphamide 500 mg/m\^2 IV days 1 and 8, (A) Brentuximab vedotin 1.2 mg/kg IV days 1 and 8, (P) Prednisone 40 mg/m\^2/day PO days 1-15, (Dac) Dacarbazine 250 mg/m\^2 IV days 1-3.). Filgrastim 5 mcg/kg subcutaneous (SC) as clinically indicated. For those with lymph nodes that do not go into remission after 2 courses of AEPA chemotherapy, radiation therapy is given.
Overall Study Death	1
Overall Study Withdrawal of consent	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	AEPA/CAPDac n=77 Participants Ann Arbor stage IIB, IIIB, IVA, or IVB participants receive: 2 cycles of AEPA chemotherapy: (A) Brentuximab vedotin 1.2 mg/kg IV (intravenous) days 1, 8 and 15, (E) Etoposide 125 mg/m\^2 IV days 1-5, (P) Prednisone 60 mg/m\^2/day PO (orally) days 1-15, (A) Doxorubicin 40 mg/m\^2 IV days 1 and 15), Followed by 4 cycles of CAPDac: (C) Cyclophosphamide 500 mg/m\^2 IV days 1 and 8, (A) Brentuximab vedotin 1.2 mg/kg IV days 1 and 8, (P) Prednisone 40 mg/m\^2/day PO days 1-15, (Dac) Dacarbazine 250 mg/m\^2 IV days 1-3.). Filgrastim 5 mcg/kg subcutaneous (SC) as clinically indicated. For those with lymph nodes that do not go into remission after 2 courses of AEPA chemotherapy, radiation therapy is given.
Age, Continuous	16 years n=3 Participants
Sex: Female, Male Female	39 Participants n=3 Participants
Sex: Female, Male Male	38 Participants n=3 Participants
Race/Ethnicity, Customized Asian	4 Participants n=3 Participants
Race/Ethnicity, Customized Black or African American	17 Participants n=3 Participants
Race/Ethnicity, Customized White	50 Participants n=3 Participants
Race/Ethnicity, Customized More than one race	4 Participants n=3 Participants
Race/Ethnicity, Customized Others	2 Participants n=3 Participants
Region of Enrollment United States · St. Jude Children's Research Hospital	59 Participants n=3 Participants
Region of Enrollment United States · Stanford University Medical Center	9 Participants n=3 Participants
Region of Enrollment United States · Dana Farber Cancer Institute	4 Participants n=3 Participants
Region of Enrollment United States · Maine Medical Center	1 Participants n=3 Participants
Region of Enrollment United States · Massachusetts General Hospital	2 Participants n=3 Participants
Region of Enrollment United States · St. Jude Midwest Affiliate	2 Participants n=3 Participants
Histology Nodular sclerosing	59 Participants n=3 Participants
Histology Classical, NOS	11 Participants n=3 Participants
Histology Lymphocyte rich	4 Participants n=3 Participants
Histology Mixed cellularity	3 Participants n=3 Participants
Stage IIB	13 Participants n=3 Participants
Stage IIIB	19 Participants n=3 Participants
Stage IVA	12 Participants n=3 Participants
Stage IVB	33 Participants n=3 Participants

PRIMARY outcome

Timeframe: After the first 2 cycles of chemotherapy (at approximately 2 months after enrollment)

Population: The first 32 evaluable participants enrolled was evaluated.

To determine the efficacy of 2 cycles of AEPA chemotherapy, the response rate for the first 32 evaluable participants enrolled was evaluated. If it shown efficacy (detect 20% increase complete rate with 80% power and 5% type I error compared with the proportion of historical control of HOD99 (NCT00145600) unfavorable risk patients had complete rate at week 8 of 17% (24/141), the response results will be reported in a national/international meeting and the study will continue to enroll for a total of 77 patients.

Outcome measures

Measure	AEPA Chemotherapy n=32 Participants Ann Arbor stage IIB, IIIB, IVA, or IVB risk participants receive 2 cycles of AEPA chemotherapy (brentuximab vedotin, etoposide, prednisone, doxorubicin)	Timepoint 10 (T10) 4-6 weeks after chemotherapy or 4-6 weeks after radiation	Timepoint 11 (T11) 1 year off therapy	Timepoint 12 (T12) 2 years off therapy (approximately 2 years and 8 months	Timepoint 13 (T13) 5 years off therapy (approximately 5 years and 8 months)	Timepoint 4 (T4) Course 2 Day 1	Timepoint 6 (T6) Course 3 Day 1	Timepoint 8 (T8) Course 6 Day 1	Cycle 5 - Grade 2 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 5 - Grade 3-4 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 6 - Grade 2 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 6 - Grade 3-4 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV
Percentage of Initially Enrolled Patients That Have a Complete Response at Early Response Assessment Compared to Historical Control	31.25 percentage of participants Interval 18.04 to 47.21	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: After the first 2 cycles of chemotherapy (at approximately 2 months after enrollment)

Population: The first 32 evaluable participants enrolled was evaluated.

To determine the efficacy of 2 cycles of AEPA chemotherapy, the response rate for the first 32 evaluable participants enrolled was evaluated. If it shown efficacy (detect 20% increase complete rate with 80% power and 5% type I error compared with the proportion of historical control of HOD99 unfavorable risk patients had complete rate at week 8 of 17% (24/141), the response results will be reported in a national/international meeting and the study will continue to enroll for a total of 77 patients.

Outcome measures

Measure	AEPA Chemotherapy n=32 Participants Ann Arbor stage IIB, IIIB, IVA, or IVB risk participants receive 2 cycles of AEPA chemotherapy (brentuximab vedotin, etoposide, prednisone, doxorubicin)	Timepoint 10 (T10) 4-6 weeks after chemotherapy or 4-6 weeks after radiation	Timepoint 11 (T11) 1 year off therapy	Timepoint 12 (T12) 2 years off therapy (approximately 2 years and 8 months	Timepoint 13 (T13) 5 years off therapy (approximately 5 years and 8 months)	Timepoint 4 (T4) Course 2 Day 1	Timepoint 6 (T6) Course 3 Day 1	Timepoint 8 (T8) Course 6 Day 1	Cycle 5 - Grade 2 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 5 - Grade 3-4 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 6 - Grade 2 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 6 - Grade 3-4 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV
Percentage of Initially Enrolled Patients That Have a Complete Response at Early Response Assessment Compared to Historical Control	31.25 percentage of participants Interval 16.12 to 50.01	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: After the first 2 cycles of chemotherapy (at 2 months from enrollment for each participant)

Population: All the evaluable participants that completed the first 2 cycles of chemotherapy.

To evaluate the safety of AEPA/CAPDac, as well as the efficacy (early complete response) after 2 cycles of AEPA chemotherapy in high-risk patients with Hodgkin Lymphoma (HL).

Outcome measures

Measure	AEPA Chemotherapy n=77 Participants Ann Arbor stage IIB, IIIB, IVA, or IVB risk participants receive 2 cycles of AEPA chemotherapy (brentuximab vedotin, etoposide, prednisone, doxorubicin)	Timepoint 10 (T10) 4-6 weeks after chemotherapy or 4-6 weeks after radiation	Timepoint 11 (T11) 1 year off therapy	Timepoint 12 (T12) 2 years off therapy (approximately 2 years and 8 months	Timepoint 13 (T13) 5 years off therapy (approximately 5 years and 8 months)	Timepoint 4 (T4) Course 2 Day 1	Timepoint 6 (T6) Course 3 Day 1	Timepoint 8 (T8) Course 6 Day 1	Cycle 5 - Grade 2 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 5 - Grade 3-4 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 6 - Grade 2 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 6 - Grade 3-4 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV
Complete Response Rate Estimate for All Evaluable Participants	35 percentage of participants Interval 24.0 to 46.0	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment)

Population: For HLHR13, all the evaluable participants that treated with AEPA/CAPDac; for HOD99 Unfavorable Risk 2 Arm (UR2), all the evaluable participants that treated with Stanford V + RT.

Event-free survival (EFS) is defined as the probability of survival between the date of study enrollment to the date of first event (relapsed or progressive disease, second malignancy, or death from any cause) or to last follow-up for patients without events. Under the proportional hazard model assumption, the two-sample log-rank test used to compare the EFS between HLHR13 and historical control of HOD99 unfavorable risk 2 arm (UR2).

Outcome measures

Measure	AEPA Chemotherapy n=77 Participants Ann Arbor stage IIB, IIIB, IVA, or IVB risk participants receive 2 cycles of AEPA chemotherapy (brentuximab vedotin, etoposide, prednisone, doxorubicin)	Timepoint 10 (T10) 4-6 weeks after chemotherapy or 4-6 weeks after radiation	Timepoint 11 (T11) 1 year off therapy	Timepoint 12 (T12) 2 years off therapy (approximately 2 years and 8 months	Timepoint 13 (T13) 5 years off therapy (approximately 5 years and 8 months)	Timepoint 4 (T4) Course 2 Day 1	Timepoint 6 (T6) Course 3 Day 1	Timepoint 8 (T8) Course 6 Day 1	Cycle 5 - Grade 2 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 5 - Grade 3-4 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 6 - Grade 2 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 6 - Grade 3-4 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV
Comparison of the Event-free (EFS) Survival in High Risk HL Patients Treated With AEPA/CAPDac to the Historical Control HOD99 Unfavorable Risk 2 Arm (UR2).	0.974 probability Interval 0.951 to 0.997	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment)

Population: All the evaluable participants treated with AEPA/CAPDac.

The local failure rate within the high-risk HL participants treated with AEPA/CAPDac will be estimated with a 95% confidence interval using appropriate methods (e.g., estimate cumulative incidence in the presence of competing risks).

Outcome measures

Measure	AEPA Chemotherapy n=77 Participants Ann Arbor stage IIB, IIIB, IVA, or IVB risk participants receive 2 cycles of AEPA chemotherapy (brentuximab vedotin, etoposide, prednisone, doxorubicin)	Timepoint 10 (T10) 4-6 weeks after chemotherapy or 4-6 weeks after radiation	Timepoint 11 (T11) 1 year off therapy	Timepoint 12 (T12) 2 years off therapy (approximately 2 years and 8 months	Timepoint 13 (T13) 5 years off therapy (approximately 5 years and 8 months)	Timepoint 4 (T4) Course 2 Day 1	Timepoint 6 (T6) Course 3 Day 1	Timepoint 8 (T8) Course 6 Day 1	Cycle 5 - Grade 2 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 5 - Grade 3-4 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 6 - Grade 2 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 6 - Grade 3-4 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV
Local Failure Rate in High Risk HL Patients Treated With AEPA/CAPDac.	0.013 Probability Interval 0.0003 to 0.0702	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From enrollment to end of therapy (approximately 8 months)

Population: Toxicities reported below for the current study (HLHR13) include all reported hematological toxicities from a participant's on-study date through end of therapy.

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 NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.

Outcome measures

Measure	AEPA Chemotherapy n=77 Participants Ann Arbor stage IIB, IIIB, IVA, or IVB risk participants receive 2 cycles of AEPA chemotherapy (brentuximab vedotin, etoposide, prednisone, doxorubicin)	Timepoint 10 (T10) n=77 Participants 4-6 weeks after chemotherapy or 4-6 weeks after radiation	Timepoint 11 (T11) n=77 Participants 1 year off therapy	Timepoint 12 (T12) n=76 Participants 2 years off therapy (approximately 2 years and 8 months	Timepoint 13 (T13) n=76 Participants 5 years off therapy (approximately 5 years and 8 months)	Timepoint 4 (T4) n=77 Participants Course 2 Day 1	Timepoint 6 (T6) n=77 Participants Course 3 Day 1	Timepoint 8 (T8) n=77 Participants Course 6 Day 1	Cycle 5 - Grade 2 n=76 Participants Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 5 - Grade 3-4 n=76 Participants Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 6 - Grade 2 n=76 Participants Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 6 - Grade 3-4 n=76 Participants Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV
Descriptive of Hematological Adverse Events Leukopenia	15 Participants	8 Participants	4 Participants	5 Participants	5 Participants	49 Participants	28 Participants	23 Participants	7 Participants	2 Participants	14 Participants	5 Participants
Descriptive of Hematological Adverse Events Neutropenia	5 Participants	7 Participants	10 Participants	5 Participants	3 Participants	62 Participants	13 Participants	51 Participants	4 Participants	3 Participants	8 Participants	6 Participants
Descriptive of Hematological Adverse Events Lymphopenia	15 Participants	9 Participants	7 Participants	16 Participants	15 Participants	36 Participants	18 Participants	15 Participants	13 Participants	22 Participants	20 Participants	31 Participants
Descriptive of Hematological Adverse Events Anemia	23 Participants	6 Participants	1 Participants	6 Participants	0 Participants	12 Participants	28 Participants	5 Participants	4 Participants	1 Participants	2 Participants	1 Participants
Descriptive of Hematological Adverse Events Thrombocytopenia	3 Participants	0 Participants	2 Participants	0 Participants	1 Participants	3 Participants	2 Participants	1 Participants	0 Participants	1 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: From enrollment to end of therapy (approximately 8 months)

Population: Toxicities reported below for the current study (HLHR13) include all reported infectious toxicities from a participant's on-study date through end of therapy.

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 NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.

Outcome measures

Measure	AEPA Chemotherapy n=77 Participants Ann Arbor stage IIB, IIIB, IVA, or IVB risk participants receive 2 cycles of AEPA chemotherapy (brentuximab vedotin, etoposide, prednisone, doxorubicin)	Timepoint 10 (T10) n=77 Participants 4-6 weeks after chemotherapy or 4-6 weeks after radiation	Timepoint 11 (T11) n=77 Participants 1 year off therapy	Timepoint 12 (T12) n=76 Participants 2 years off therapy (approximately 2 years and 8 months	Timepoint 13 (T13) n=76 Participants 5 years off therapy (approximately 5 years and 8 months)	Timepoint 4 (T4) n=77 Participants Course 2 Day 1	Timepoint 6 (T6) n=77 Participants Course 3 Day 1	Timepoint 8 (T8) n=77 Participants Course 6 Day 1	Cycle 5 - Grade 2 n=76 Participants Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 5 - Grade 3-4 n=76 Participants Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 6 - Grade 2 n=76 Participants Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 6 - Grade 3-4 n=76 Participants Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV
Descriptive of Infectious Adverse Events Febrile neutropenia	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	6 Participants	0 Participants	3 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Descriptive of Infectious Adverse Events Mucositis	10 Participants	0 Participants	0 Participants	1 Participants	0 Participants	2 Participants	6 Participants	4 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Descriptive of Infectious Adverse Events Upper respiratory infection	5 Participants	0 Participants	0 Participants	0 Participants	2 Participants	2 Participants	3 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Descriptive of Infectious Adverse Events Genitourinary infection	1 Participants	2 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From enrollment to end of therapy (approximately 8 months)

Population: Toxicities reported below for the current study (HLHR13) include all reported neuropathic toxicities from a participant's on-study date through end of therapy.

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 NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.

Outcome measures

Measure	AEPA Chemotherapy n=77 Participants Ann Arbor stage IIB, IIIB, IVA, or IVB risk participants receive 2 cycles of AEPA chemotherapy (brentuximab vedotin, etoposide, prednisone, doxorubicin)	Timepoint 10 (T10) n=77 Participants 4-6 weeks after chemotherapy or 4-6 weeks after radiation	Timepoint 11 (T11) n=77 Participants 1 year off therapy	Timepoint 12 (T12) n=76 Participants 2 years off therapy (approximately 2 years and 8 months	Timepoint 13 (T13) n=76 Participants 5 years off therapy (approximately 5 years and 8 months)	Timepoint 4 (T4) n=77 Participants Course 2 Day 1	Timepoint 6 (T6) n=77 Participants Course 3 Day 1	Timepoint 8 (T8) n=77 Participants Course 6 Day 1	Cycle 5 - Grade 2 n=76 Participants Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 5 - Grade 3-4 n=76 Participants Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 6 - Grade 2 n=76 Participants Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 6 - Grade 3-4 n=76 Participants Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV
Descriptive of Neuropathic Adverse Events Pain NOS	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants
Descriptive of Neuropathic Adverse Events Pain in extremity	3 Participants	1 Participants	0 Participants	1 Participants	0 Participants	1 Participants	4 Participants	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants
Descriptive of Neuropathic Adverse Events Neuralgia	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Descriptive of Neuropathic Adverse Events Peripheral sensory neuropathy	0 Participants	2 Participants	0 Participants	3 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: At Diagnosis (baseline) (T1), completion of 2 cycles of chemotherapy (approximately 2 months) (T2), completion of 4 cycles of chemotherapy (approximately 4 months) (T3), completion of radiation (approximately 8 months) (T4)

Population: Each institution made the decision whether to complete the QoL objective. Participation in the Quality of Life part of the trial is voluntary for participating institutions and voluntary by patient. The Peds QL 3.0 data was not collected on the HOD 99 patients at the T1 time point.

Assess and compare the patient reported quality of life and symptom distress to that of patients treated on the HOD99 unfavorable risk 2 arm (UR2) using the Peds Quality of Life version 3. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. For both the total score and subscales the range is 0-100. The total score is the sum of all items from each subscale, over the number of items answered on the scale. The total score is the sum of all items on the scale over the number of items answer. If >50% of the items are missing the score should not be computed. If >50% are completed, impute the mean of the completed items in a scale. The Higher the score the better quality of life.

Outcome measures

Measure	AEPA Chemotherapy n=77 Participants Ann Arbor stage IIB, IIIB, IVA, or IVB risk participants receive 2 cycles of AEPA chemotherapy (brentuximab vedotin, etoposide, prednisone, doxorubicin)	Timepoint 10 (T10) 4-6 weeks after chemotherapy or 4-6 weeks after radiation	Timepoint 11 (T11) 1 year off therapy	Timepoint 12 (T12) 2 years off therapy (approximately 2 years and 8 months	Timepoint 13 (T13) 5 years off therapy (approximately 5 years and 8 months)	Timepoint 4 (T4) n=146 Participants Course 2 Day 1	Timepoint 6 (T6) Course 3 Day 1	Timepoint 8 (T8) Course 6 Day 1	Cycle 5 - Grade 2 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 5 - Grade 3-4 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 6 - Grade 2 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 6 - Grade 3-4 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Total Score-T1	73.38 score on a scale Standard Deviation 15.97	—	—	—	—	—	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Total Score-T2	80.41 score on a scale Standard Deviation 14.68	—	—	—	—	71.92 score on a scale Standard Deviation 14.58	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Total Score-T3	83.33 score on a scale Standard Deviation 13.87	—	—	—	—	73.78 score on a scale Standard Deviation 17.72	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Total Score-T4	85.33 score on a scale Standard Deviation 13.62	—	—	—	—	79.92 score on a scale Standard Deviation 16.25	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Pain and Hurt-T1	73.41 score on a scale Standard Deviation 27.45	—	—	—	—	—	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Pain and Hurt-T2	71.77 score on a scale Standard Deviation 29.94	—	—	—	—	66.09 score on a scale Standard Deviation 27.49	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Pain and Hurt-T3	72.63 score on a scale Standard Deviation 30.03	—	—	—	—	69.81 score on a scale Standard Deviation 29.34	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Pain and Hurt-T4	77.5 score on a scale Standard Deviation 30.3	—	—	—	—	82.2 score on a scale Standard Deviation 25.39	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Nausea-T1	73.97 score on a scale Standard Deviation 21.2	—	—	—	—	—	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Nausea-T2	75.52 score on a scale Standard Deviation 23.92	—	—	—	—	60.5 score on a scale Standard Deviation 23.83	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Nausea-T3	79.66 score on a scale Standard Deviation 20.73	—	—	—	—	60.26 score on a scale Standard Deviation 26.92	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Nausea-T4	88.1 score on a scale Standard Deviation 17.67	—	—	—	—	78.13 score on a scale Standard Deviation 22.69	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Procedural Anxiety-T1	58.6 score on a scale Standard Deviation 37	—	—	—	—	—	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Procedural Anxiety-T2	77.55 score on a scale Standard Deviation 26.64	—	—	—	—	71.17 score on a scale Standard Deviation 27.72	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Procedural Anxiety-T3	81.61 score on a scale Standard Deviation 24.47	—	—	—	—	73.46 score on a scale Standard Deviation 27.98	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Procedural Anxiety-T4	76.83 score on a scale Standard Deviation 30.36	—	—	—	—	77.65 score on a scale Standard Deviation 24.2	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Treatment Anxiety-T1	84.52 score on a scale Standard Deviation 21.47	—	—	—	—	—	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Treatment Anxiety-T2	91.39 score on a scale Standard Deviation 14.67	—	—	—	—	85.92 score on a scale Standard Deviation 17.06	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Treatment Anxiety-T3	93.97 score on a scale Standard Deviation 12.37	—	—	—	—	85.06 score on a scale Standard Deviation 23.11	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Treatment Anxiety-T4	93.17 score on a scale Standard Deviation 13.95	—	—	—	—	83.71 score on a scale Standard Deviation 22.9	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Worry-T1	69.22 score on a scale Standard Deviation 24.08	—	—	—	—	—	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Worry-T2	77.55 score on a scale Standard Deviation 22.51	—	—	—	—	64.63 score on a scale Standard Deviation 25.01	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Worry-T3	84.2 score on a scale Standard Deviation 17.01	—	—	—	—	66.45 score on a scale Standard Deviation 25.33	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Worry-T4	82.17 score on a scale Standard Deviation 20.89	—	—	—	—	69.57 score on a scale Standard Deviation 29.58	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Cognitive Problems-T1	72.34 score on a scale Standard Deviation 23.09	—	—	—	—	—	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Cognitive Problems-T2	81.25 score on a scale Standard Deviation 21.06	—	—	—	—	75.72 score on a scale Standard Deviation 19.48	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Cognitive Problems-T3	84.38 score on a scale Standard Deviation 19.41	—	—	—	—	78.38 score on a scale Standard Deviation 22.03	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Cognitive Problems-T4	87.04 score on a scale Standard Deviation 18.95	—	—	—	—	81.69 score on a scale Standard Deviation 17.84	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Perceived Physical Appearance-T1	79.64 score on a scale Standard Deviation 25.21	—	—	—	—	—	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Perceived Physical Appearance-T2	83.53 score on a scale Standard Deviation 22.99	—	—	—	—	78.07 score on a scale Standard Deviation 24.91	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Perceived Physical Appearance-T3	82.69 score on a scale Standard Deviation 22.29	—	—	—	—	79.87 score on a scale Standard Deviation 22.47	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Perceived Physical Appearance-T4	85.17 score on a scale Standard Deviation 22.48	—	—	—	—	79.95 score on a scale Standard Deviation 23.79	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Communication-T1	74.6 score on a scale Standard Deviation 27.3	—	—	—	—	—	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Communication-T2	85.38 score on a scale Standard Deviation 20.73	—	—	—	—	79.02 score on a scale Standard Deviation 18.58	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Communication-T3	85.34 score on a scale Standard Deviation 20.9	—	—	—	—	81.93 score on a scale Standard Deviation 21.22	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.3.0) PedsQL v.3.0 Communication-T4	87.33 score on a scale Standard Deviation 17.6	—	—	—	—	84.24 score on a scale Standard Deviation 21.16	—	—	—	—	—	—

SECONDARY outcome

Timeframe: At Diagnosis (baseline) (T1), completion of 2 cycles of chemotherapy (approximately 2 months) (T2), completion of 4 cycles of chemotherapy (approximately 4 months) (T3), completion of radiation (approximately 8 months) (T4)

Population: Each institution made the decision whether to complete the QoL objective. Participation in the Quality of Life part of the trial is voluntary for participating institutions and voluntary by patient.

Assess and compare the patient reported quality of life and symptom distress to that of patients treated on the HOD99 unfavorable risk 2 arm (UR2) using the Peds Quality of Life version 4. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. For both the total score and subscales the range is 0-100. The total score is the sum of all items from each subscale, over the number of items answered on the scale. The total score is the sum of all items on the scale over the number of items answer. If >50% of the items are missing the score should not be computed. If >50% are completed, impute the mean of the completed items in a scale. The Higher the score the better quality of life.

Outcome measures

Measure	AEPA Chemotherapy n=77 Participants Ann Arbor stage IIB, IIIB, IVA, or IVB risk participants receive 2 cycles of AEPA chemotherapy (brentuximab vedotin, etoposide, prednisone, doxorubicin)	Timepoint 10 (T10) 4-6 weeks after chemotherapy or 4-6 weeks after radiation	Timepoint 11 (T11) 1 year off therapy	Timepoint 12 (T12) 2 years off therapy (approximately 2 years and 8 months	Timepoint 13 (T13) 5 years off therapy (approximately 5 years and 8 months)	Timepoint 4 (T4) n=146 Participants Course 2 Day 1	Timepoint 6 (T6) Course 3 Day 1	Timepoint 8 (T8) Course 6 Day 1	Cycle 5 - Grade 2 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 5 - Grade 3-4 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 6 - Grade 2 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 6 - Grade 3-4 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.4.0) PedsQL v.4.0 Total Score-T1	72.94 score on a scale Standard Deviation 17.63	—	—	—	—	72.48 score on a scale Standard Deviation 17.37	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.4.0) PedsQL v.4.0 Total Score-T2	79.38 score on a scale Standard Deviation 17.43	—	—	—	—	73.54 score on a scale Standard Deviation 16.71	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.4.0) PedsQL v.4.0 Total Score-T3	80.39 score on a scale Standard Deviation 14.96	—	—	—	—	77.68 score on a scale Standard Deviation 17.25	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.4.0) PedsQL v.4.0 Total Score-T4	86.06 score on a scale Standard Deviation 14.53	—	—	—	—	84.58 score on a scale Standard Deviation 15.02	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.4.0) PedsQL v.4.0 Physical Functioning-T1	69.54 score on a scale Standard Deviation 21.78	—	—	—	—	70.41 score on a scale Standard Deviation 26.09	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.4.0) PedsQL v.4.0 Physical Functioning-T2	73.86 score on a scale Standard Deviation 24.14	—	—	—	—	70.06 score on a scale Standard Deviation 22.73	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.4.0) PedsQL v.4.0 Physical Functioning-T3	74.02 score on a scale Standard Deviation 22.13	—	—	—	—	72.94 score on a scale Standard Deviation 25.25	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.4.0) PedsQL v.4.0 Physical Functioning-T4	82.45 score on a scale Standard Deviation 23.24	—	—	—	—	83.57 score on a scale Standard Deviation 18.86	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.4.0) PedsQL v.4.0 Emotional Functioning-T1	71.75 score on a scale Standard Deviation 24.38	—	—	—	—	67.18 score on a scale Standard Deviation 18.25	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.4.0) PedsQL v.4.0 Emotional Functioning-T2	83.06 score on a scale Standard Deviation 16.63	—	—	—	—	71.31 score on a scale Standard Deviation 20.96	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.4.0) PedsQL v.4.0 Emotional Functioning-T3	82.07 score on a scale Standard Deviation 18.43	—	—	—	—	75.06 score on a scale Standard Deviation 22.38	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.4.0) PedsQL v.4.0 Emotional Functioning-T4	84.81 score on a scale Standard Deviation 19.75	—	—	—	—	80.87 score on a scale Standard Deviation 20.63	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.4.0) PedsQL v.4.0 Social Functioning-T1	86.21 score on a scale Standard Deviation 17.05	—	—	—	—	86.22 score on a scale Standard Deviation 17.69	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.4.0) PedsQL v.4.0 Social Functioning-T2	88.47 score on a scale Standard Deviation 15.85	—	—	—	—	86.82 score on a scale Standard Deviation 15.42	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.4.0) PedsQL v.4.0 Social Functioning-T3	90.22 score on a scale Standard Deviation 12.41	—	—	—	—	88.86 score on a scale Standard Deviation 13.84	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.4.0) PedsQL v.4.0 Social Functioning-T4	92.31 score on a scale Standard Deviation 11.57	—	—	—	—	91.44 score on a scale Standard Deviation 14.35	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.4.0) PedsQL v.4.0 School Functioning-T1	65.49 score on a scale Standard Deviation 22.72	—	—	—	—	67.82 score on a scale Standard Deviation 19.65	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.4.0) PedsQL v.4.0 School Functioning-T2	75.66 score on a scale Standard Deviation 24.66	—	—	—	—	66.91 score on a scale Standard Deviation 21.79	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.4.0) PedsQL v.4.0 School Functioning-T3	79.2 score on a scale Standard Deviation 21.49	—	—	—	—	69.1 score on a scale Standard Deviation 24.27	—	—	—	—	—	—
To Assess the 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 (UR2) at Multiple Time Points. (PedsQL v.4.0) PedsQL v.4.0 School Functioning-T4	86.9 score on a scale Standard Deviation 18.62	—	—	—	—	79.32 score on a scale Standard Deviation 17.77	—	—	—	—	—	—

SECONDARY outcome

Timeframe: after the first 2 cycles of chemotherapy (at approximately 2 months after enrollment)

Response compared to the Euro-Net C1 after 2 cycles of AEPA.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At various time points from diagnosis through 5 years off therapy. (up to approximately 6 years from enrollment).

Population: Each institution made the decision whether to complete the QoL objective. Participation in the Quality of Life part of the trial is voluntary for participating institutions and voluntary by patient.

Patient QOL will be measured at multiple time points to assess the patient's physical emotional, social, and school functioning.

The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. For both the total score and subscales the range is 0-100. The total score is the sum of all items from each subscale, over the number of items answered on the scale. The total score is the sum of all items on the scale over the number of items answer. If >50% of the items are missing the score should not be computed. If >50% are completed, impute the mean of the completed items in a scale. The Higher the score the better quality of life.

Outcome measures

Measure	AEPA Chemotherapy n=63 Participants Ann Arbor stage IIB, IIIB, IVA, or IVB risk participants receive 2 cycles of AEPA chemotherapy (brentuximab vedotin, etoposide, prednisone, doxorubicin)	Timepoint 10 (T10) n=52 Participants 4-6 weeks after chemotherapy or 4-6 weeks after radiation	Timepoint 11 (T11) n=51 Participants 1 year off therapy	Timepoint 12 (T12) n=39 Participants 2 years off therapy (approximately 2 years and 8 months	Timepoint 13 (T13) n=35 Participants 5 years off therapy (approximately 5 years and 8 months)	Timepoint 4 (T4) n=64 Participants Course 2 Day 1	Timepoint 6 (T6) n=62 Participants Course 3 Day 1	Timepoint 8 (T8) n=58 Participants Course 6 Day 1	Cycle 5 - Grade 2 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 5 - Grade 3-4 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 6 - Grade 2 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 6 - Grade 3-4 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV
Patient Quality of Life (QoL) Physical Functioning	69.5 score on a scale Standard Deviation 21.8	82.5 score on a scale Standard Deviation 23.2	87.7 score on a scale Standard Deviation 20.3	87.1 score on a scale Standard Deviation 20.7	88.8 score on a scale Standard Deviation 19.4	75.8 score on a scale Standard Deviation 21.8	73.9 score on a scale Standard Deviation 24.1	74 score on a scale Standard Deviation 22.1	—	—	—	—
Patient Quality of Life (QoL) Emotional Functioning	71.7 score on a scale Standard Deviation 24.4	84.8 score on a scale Standard Deviation 19.8	88.4 score on a scale Standard Deviation 18.8	88.2 score on a scale Standard Deviation 16.4	80.9 score on a scale Standard Deviation 22.8	80.3 score on a scale Standard Deviation 20.2	83.1 score on a scale Standard Deviation 16.6	82.1 score on a scale Standard Deviation 18.4	—	—	—	—
Patient Quality of Life (QoL) Social Functioning	86.2 score on a scale Standard Deviation 17	92.3 score on a scale Standard Deviation 11.6	93.8 score on a scale Standard Deviation 11.9	94 score on a scale Standard Deviation 12.8	95.3 score on a scale Standard Deviation 12.2	87.2 score on a scale Standard Deviation 18.3	88.5 score on a scale Standard Deviation 15.9	90.2 score on a scale Standard Deviation 12.4	—	—	—	—
Patient Quality of Life (QoL) School Functioning	65.5 score on a scale Standard Deviation 22.7	86.9 score on a scale Standard Deviation 18.6	85.4 score on a scale Standard Deviation 16.2	87.2 score on a scale Standard Deviation 13.1	81.5 score on a scale Standard Deviation 23.1	75.7 score on a scale Standard Deviation 24.3	75.7 score on a scale Standard Deviation 24.7	79.2 score on a scale Standard Deviation 21.5	—	—	—	—

SECONDARY outcome

Timeframe: At various time points from diagnosis through 5 years off therapy. (up to approximately 6 years from enrollment)

Population: Each institution made the decision whether to complete the QoL objective. Participation in the Quality of Life part of the trial is voluntary for participating institutions and voluntary by parent.

Parent's assessment of child's physical, emotional, social and school functioning over multiple time points.

The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. For both the total score and subscales the range is 0-100. The total score is the sum of all items from each subscale, over the number of items answered on the scale. The total score is the sum of all items on the scale over the number of items answer. If >50% of the items are missing the score should not be computed. If >50% are completed, impute the mean of the completed items in a scale. The Higher the score the better quality of life.

Outcome measures

Measure	AEPA Chemotherapy n=62 Participants Ann Arbor stage IIB, IIIB, IVA, or IVB risk participants receive 2 cycles of AEPA chemotherapy (brentuximab vedotin, etoposide, prednisone, doxorubicin)	Timepoint 10 (T10) n=46 Participants 4-6 weeks after chemotherapy or 4-6 weeks after radiation	Timepoint 11 (T11) n=41 Participants 1 year off therapy	Timepoint 12 (T12) n=30 Participants 2 years off therapy (approximately 2 years and 8 months	Timepoint 13 (T13) n=10 Participants 5 years off therapy (approximately 5 years and 8 months)	Timepoint 4 (T4) n=60 Participants Course 2 Day 1	Timepoint 6 (T6) n=57 Participants Course 3 Day 1	Timepoint 8 (T8) n=55 Participants Course 6 Day 1	Cycle 5 - Grade 2 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 5 - Grade 3-4 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 6 - Grade 2 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 6 - Grade 3-4 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV
Parent Proxy Quality of Life (QoL) Physical Functioning	61.8 score on a scale Standard Deviation 26.9	74.5 score on a scale Standard Deviation 25.6	76.6 score on a scale Standard Deviation 29.0	75 score on a scale Standard Deviation 26.4	84.7 score on a scale Standard Deviation 29.1	65.3 score on a scale Standard Deviation 20.8	66.8 score on a scale Standard Deviation 22.3	65.6 score on a scale Standard Deviation 24.1	—	—	—	—
Parent Proxy Quality of Life (QoL) Emotional Functioning	61.9 score on a scale Standard Deviation 23.1	78.6 score on a scale Standard Deviation 21	84.2 score on a scale Standard Deviation 20.3	79 score on a scale Standard Deviation 23.3	85.5 score on a scale Standard Deviation 19.2	69.3 score on a scale Standard Deviation 25.2	72 score on a scale Standard Deviation 22.5	73.7 score on a scale Standard Deviation 21.4	—	—	—	—
Parent Proxy Quality of Life (QoL) Social Functioning	80.3 score on a scale Standard Deviation 18.8	84.5 score on a scale Standard Deviation 20.1	87.8 score on a scale Standard Deviation 17.9	82.5 score on a scale Standard Deviation 22.8	92.6 score on a scale Standard Deviation 13.5	79.2 score on a scale Standard Deviation 21.6	79.6 score on a scale Standard Deviation 18.4	79.2 score on a scale Standard Deviation 19.8	—	—	—	—
Parent Proxy Quality of Life (QoL) School Functioning	63.2 score on a scale Standard Deviation 25.4	80.3 score on a scale Standard Deviation 21.7	82.2 score on a scale Standard Deviation 22.9	78.2 score on a scale Standard Deviation 22.5	81 score on a scale Standard Deviation 19.4	68.5 score on a scale Standard Deviation 25.6	67.1 score on a scale Standard Deviation 25.3	70.5 score on a scale Standard Deviation 25.2	—	—	—	—

SECONDARY outcome

Timeframe: At various time points from diagnosis through 5 years off therapy. (up to approximately 6 years from enrollment)

Population: Each institution made the decision whether to complete the QoL objective. Participation in the Quality of Life part of the trial is voluntary for participating institutions and voluntary by participant.

The correlation of agreement between patient and parent Quality of Life is calculated by using the Pearson's Correlation Coefficient, which considers only the record with both parent and patient data.

The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. For both the total score and subscales the range is 0-100. The total score is the sum of all items from each subscale, over the number of items answered on the scale. The total score is the sum of all items on the scale over the number of items answer. If >50% of the items are missing the score should not be computed. If >50% are completed, impute the mean of the completed items in a scale. The Higher the score the better quality of life.

Outcome measures

Measure	AEPA Chemotherapy n=62 Participants Ann Arbor stage IIB, IIIB, IVA, or IVB risk participants receive 2 cycles of AEPA chemotherapy (brentuximab vedotin, etoposide, prednisone, doxorubicin)	Timepoint 10 (T10) n=45 Participants 4-6 weeks after chemotherapy or 4-6 weeks after radiation	Timepoint 11 (T11) n=41 Participants 1 year off therapy	Timepoint 12 (T12) n=30 Participants 2 years off therapy (approximately 2 years and 8 months	Timepoint 13 (T13) n=10 Participants 5 years off therapy (approximately 5 years and 8 months)	Timepoint 4 (T4) n=60 Participants Course 2 Day 1	Timepoint 6 (T6) n=56 Participants Course 3 Day 1	Timepoint 8 (T8) n=54 Participants Course 6 Day 1	Cycle 5 - Grade 2 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 5 - Grade 3-4 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 6 - Grade 2 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV	Cycle 6 - Grade 3-4 Participants receive CAPDac regimen for 4 cycles (cycle length 21 days): (C) Cyclophosphamide IV 500 mg/m\^2 (A) Brentuximab vedotin 1.2 mg/kg IV (P) Prednisone 40 mg/40 mg/m\^2/day PO (Dac) Dacarbazine 250 mg/m\^2 IV
Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points Physical Functioning	0.701 correlation coefficient Interval 0.547 to 0.809	0.406 correlation coefficient Interval 0.128 to 0.625	0.528 correlation coefficient Interval 0.263 to 0.719	0.468 correlation coefficient Interval 0.129 to 0.709	0.294 correlation coefficient Interval -0.411 to 0.78	0.503 correlation coefficient Interval 0.286 to 0.671	0.536 correlation coefficient Interval 0.318 to 0.7	0.575 correlation coefficient Interval 0.363 to 0.73	—	—	—	—
Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points Social Functioning	0.309 correlation coefficient Interval 0.064 to 0.518	0.086 correlation coefficient Interval -0.213 to 0.371	0.327 correlation coefficient Interval 0.021 to 0.577	0.135 correlation coefficient Interval -0.236 to 0.473	-0.027 correlation coefficient Interval -0.645 to 0.613	0.566 correlation coefficient Interval 0.362 to 0.718	0.534 correlation coefficient Interval 0.313 to 0.7	0.242 correlation coefficient Interval -0.028 to 0.479	—	—	—	—
Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points Emotional Functioning	0.593 correlation coefficient Interval 0.402 to 0.734	0.344 correlation coefficient Interval 0.056 to 0.579	0.671 correlation coefficient Interval 0.457 to 0.811	0.291 correlation coefficient Interval -0.077 to 0.59	0.756 correlation coefficient Interval 0.24 to 0.939	0.664 correlation coefficient Interval 0.491 to 0.786	0.648 correlation coefficient Interval 0.464 to 0.778	0.588 correlation coefficient Interval 0.38 to 0.739	—	—	—	—
Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points School Functioning	0.444 correlation coefficient Interval 0.211 to 0.628	0.694 correlation coefficient Interval 0.488 to 0.827	0.315 correlation coefficient Interval 0.004 to 0.57	0.209 correlation coefficient Interval -0.17 to 0.535	0.574 correlation coefficient Interval -0.088 to 0.884	0.577 correlation coefficient Interval 0.364 to 0.733	0.501 correlation coefficient Interval 0.261 to 0.682	0.441 correlation coefficient Interval 0.188 to 0.639	—	—	—	—

Adverse Events

AEPA/CAPDac

Serious events: 2 serious events

Other events: 75 other events

Deaths: 1 deaths

Serious adverse events

Measure	AEPA/CAPDac n=77 participants at risk Ann Arbor stage IIB, IIIB, IVA, or IVB participants receive: 2 cycles of AEPA chemotherapy: (A) Brentuximab vedotin 1.2 mg/kg IV (intravenous) days 1, 8 and 15, (E) Etoposide 125 mg/m\^2 IV days 1-5, (P) Prednisone 60 mg/m\^2/day PO (orally) days 1-15, (A) Doxorubicin 40 mg/m\^2 IV days 1 and 15), Followed by 4 cycles of CAPDac: (C) Cyclophosphamide 500 mg/m\^2 IV days 1 and 8, (A) Brentuximab vedotin 1.2 mg/kg IV days 1 and 8, (P) Prednisone 40 mg/m\^2/day PO days 1-15, (Dac) Dacarbazine 250 mg/m\^2 IV days 1-3.). Filgrastim 5 mcg/kg subcutaneous (SC) as clinically indicated. For those with lymph nodes that do not go into remission after 2 courses of AEPA chemotherapy, radiation therapy is given.
Cardiac disorders Ventricular tachycardia	1.3% 1/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Investigations Neutrophil count decreased	1.3% 1/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).

Other adverse events

Measure	AEPA/CAPDac n=77 participants at risk Ann Arbor stage IIB, IIIB, IVA, or IVB participants receive: 2 cycles of AEPA chemotherapy: (A) Brentuximab vedotin 1.2 mg/kg IV (intravenous) days 1, 8 and 15, (E) Etoposide 125 mg/m\^2 IV days 1-5, (P) Prednisone 60 mg/m\^2/day PO (orally) days 1-15, (A) Doxorubicin 40 mg/m\^2 IV days 1 and 15), Followed by 4 cycles of CAPDac: (C) Cyclophosphamide 500 mg/m\^2 IV days 1 and 8, (A) Brentuximab vedotin 1.2 mg/kg IV days 1 and 8, (P) Prednisone 40 mg/m\^2/day PO days 1-15, (Dac) Dacarbazine 250 mg/m\^2 IV days 1-3.). Filgrastim 5 mcg/kg subcutaneous (SC) as clinically indicated. For those with lymph nodes that do not go into remission after 2 courses of AEPA chemotherapy, radiation therapy is given.
Metabolism and nutrition disorders Hypoalbuminemia	46.8% 36/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Gastrointestinal disorders Vomiting	44.2% 34/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Investigations Aspartate aminotransferase increased	36.4% 28/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Gastrointestinal disorders Constipation	33.8% 26/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Respiratory, thoracic and mediastinal disorders Cough	32.5% 25/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Nervous system disorders Headache	31.2% 24/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Gastrointestinal disorders Mucositis oral	29.9% 23/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Metabolism and nutrition disorders Hyponatremia	29.9% 23/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Metabolism and nutrition disorders Hypocalcemia	28.6% 22/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Musculoskeletal and connective tissue disorders Pain in extremity	28.6% 22/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Gastrointestinal disorders Diarrhea	26.0% 20/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Gastrointestinal disorders Abdominal pain	24.7% 19/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Metabolism and nutrition disorders Hypokalemia	24.7% 19/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
General disorders Fatigue	23.4% 18/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Gastrointestinal disorders Nausea	64.9% 50/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Metabolism and nutrition disorders Hyperglycemia	50.6% 39/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Investigations Neutrophil count decreased	97.4% 75/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Investigations Lymphocyte count decreased	96.1% 74/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Investigations White blood cell decreased	94.8% 73/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Blood and lymphatic system disorders Anemia	92.2% 71/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Investigations Alanine aminotransferase increased	72.7% 56/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Investigations Weight gain	71.4% 55/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Investigations Platelet count decreased	66.2% 51/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Gastrointestinal disorders Gastroesophageal reflux disease	22.1% 17/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
General disorders Fever	22.1% 17/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Skin and subcutaneous tissue disorders Alopecia	22.1% 17/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Metabolism and nutrition disorders Hypophosphatemia	20.8% 16/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Musculoskeletal and connective tissue disorders Back pain	20.8% 16/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Nervous system disorders Peripheral sensory neuropathy	18.2% 14/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Psychiatric disorders Insomnia	18.2% 14/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Metabolism and nutrition disorders Hyperkalemia	16.9% 13/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
General disorders Pain	15.6% 12/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Skin and subcutaneous tissue disorders Dry skin	15.6% 12/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Infections and infestations Upper respiratory infection	14.3% 11/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Psychiatric disorders Anxiety	14.3% 11/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Respiratory, thoracic and mediastinal disorders Nasal congestion	14.3% 11/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Respiratory, thoracic and mediastinal disorders Sore throat	14.3% 11/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Metabolism and nutrition disorders Hypermagnesemia	13.0% 10/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Nervous system disorders Paresthesia	13.0% 10/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify	13.0% 10/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Skin and subcutaneous tissue disorders Pruritus	13.0% 10/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Metabolism and nutrition disorders Hypomagnesemia	11.7% 9/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Musculoskeletal and connective tissue disorders Arthralgia	11.7% 9/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Psychiatric disorders Depression	11.7% 9/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Injury, poisoning and procedural complications Infusion related reaction	10.4% 8/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
General disorders Non-cardiac chest pain	10.4% 8/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Investigations Weight loss	10.4% 8/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Musculoskeletal and connective tissue disorders Avascular necrosis	10.4% 8/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Musculoskeletal and connective tissue disorders Myalgia	10.4% 8/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Skin and subcutaneous tissue disorders Rash maculo-papular	10.4% 8/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Gastrointestinal disorders Oral pain	9.1% 7/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Metabolism and nutrition disorders Hypercalcemia	9.1% 7/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Metabolism and nutrition disorders Hypoglycemia	9.1% 7/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Nervous system disorders Dizziness	9.1% 7/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Skin and subcutaneous tissue disorders Rash acneiform	9.1% 7/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Blood and lymphatic system disorders Febrile neutropenia	7.8% 6/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Eye disorders Blurred vision	7.8% 6/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Gastrointestinal disorders Dyspepsia	7.8% 6/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Metabolism and nutrition disorders Anorexia	7.8% 6/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Metabolism and nutrition disorders Dehydration	7.8% 6/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Musculoskeletal and connective tissue disorders Bone pain	7.8% 6/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	7.8% 6/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Cardiac disorders Sinus tachycardia	6.5% 5/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Gastrointestinal disorders Dental caries	6.5% 5/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
General disorders Edema limbs	6.5% 5/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Infections and infestations Infections and infestations - Other, specify	6.5% 5/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Infections and infestations Mucosal infection	6.5% 5/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Infections and infestations Skin infection	6.5% 5/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Injury, poisoning and procedural complications Fall	6.5% 5/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Injury, poisoning and procedural complications Vascular access complication	6.5% 5/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Eye disorders Dry eye	5.2% 4/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Gastrointestinal disorders Colitis	5.2% 4/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Gastrointestinal disorders Esophageal pain	5.2% 4/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
General disorders Malaise	5.2% 4/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Infections and infestations Catheter related infection	5.2% 4/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Injury, poisoning and procedural complications Fracture	5.2% 4/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Musculoskeletal and connective tissue disorders Chest wall pain	5.2% 4/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Nervous system disorders Tremor	5.2% 4/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Respiratory, thoracic and mediastinal disorders Epistaxis	5.2% 4/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Respiratory, thoracic and mediastinal disorders Postnasal drip	5.2% 4/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Vascular disorders Hot flashes	5.2% 4/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Vascular disorders Hypertension	5.2% 4/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Vascular disorders Hypotension	5.2% 4/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).
Vascular disorders Thromboembolic event	5.2% 4/77 • Acute adverse events were collected from each participant's on-study date through the end of therapy, through study completion, an average of 1 year. The timeframe for All-Cause Mortality was from start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment).

Additional Information

Matt Ehrhardt, MD

St. Jude Children's Research Hospital

Phone: (901) 595-5913

Email: matt.ehrhardt@stjude.org

Results disclosure agreements

• Principal investigator is a sponsor employee MSA states Site is unable to publish until all completed case report forms have been delivered to Sponsor, (Study Completion). Site shall have the right to publish after publication of a multi-center publication coordinated by the Sponsor or (12) mths. after Study Completion; provided, that prior to any such publication or public release of such data, Site shall furnish Sponsor with a copy of any proposed publication at least (45)days in advance of the proposed publication or presentation date.
• Publication restrictions are in place

Restriction type: OTHER