Trial Outcomes & Findings for A Frontline Therapy Trial in Participants With Advanced Classical Hodgkin Lymphoma (NCT NCT01712490)

Last Updated: 2025-11-10

Results Overview

mPFS was defined as the time from the date of randomization to the date of the first of documentation of progressive disease (PD), death due to any cause, or for participants who were confirmed non complete responders per IRF, receipt of subsequent anticancer therapy for Hodgkin lymphoma (HL) after completion of frontline therapy. PD was defined as any new lesion or increase by greater than or equal to (\>=) 50 percent (%) of previously involved sites from nadir. Frontline therapy is the part of standard set of treatments.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

1334 participants

Primary outcome timeframe

Baseline until PD or death or receipt of any subsequent anticancer therapy for HL after completion of frontline therapy (approximately up to 4 years)

Results posted on

2025-11-10

Participant Flow

Participants took part in the study at 218 investigative sites in Asia Pacific, Europe, Latin America, and North America from 09 November 2012 to the primary completion date of 20 April 2017.

Participants with histologically confirmed diagnosis of advanced classical hodgkin lymphoma (cHL) were enrolled to receive: brentuximab vedotin 1.2 mg/kg plus doxorubicin 25 mg/m\^2, vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2 (A+AVD) or doxorubicin 25 mg/m\^2, bleomycin 10 units/m\^2, vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2 (ABVD).

Participant milestones

Participant milestones
Measure	A+AVD Brentuximab vedotin 1.2 milligram per kilogram (mg/kg), infusion, intravenously over 30-minutes plus doxorubicin 25 milligram per square meter (mg/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles. Brentuximab vedotin was administered within approximately 1 hour after completion of AVD.	ABVD Doxorubicin 25 mg/m\^2, bleomycin 10 units per square meter (units/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles.
Overall Study STARTED	664	670
Overall Study Treated	662	659
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	664	670

Reasons for withdrawal

Reasons for withdrawal
Measure	A+AVD Brentuximab vedotin 1.2 milligram per kilogram (mg/kg), infusion, intravenously over 30-minutes plus doxorubicin 25 milligram per square meter (mg/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles. Brentuximab vedotin was administered within approximately 1 hour after completion of AVD.	ABVD Doxorubicin 25 mg/m\^2, bleomycin 10 units per square meter (units/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles.
Overall Study Ongoing	601	586
Overall Study Other	11	11
Overall Study Withdrawal by Subject	36	44
Overall Study Lost to Follow-up	16	29

Baseline Characteristics

The ITT population included all participants randomized to treatment.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	A+AVD n=664 Participants Brentuximab vedotin 1.2 milligram per kilogram (mg/kg), infusion, intravenously over 30-minutes plus doxorubicin 25 milligram per square meter (mg/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles. Brentuximab vedotin was administered within approximately 1 hour after completion of AVD.	ABVD n=670 Participants Doxorubicin 25 mg/m\^2, bleomycin 10 units per square meter (units/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles.	Total n=1334 Participants Total of all reporting groups
Ethnicity (NIH/OMB) Hispanic or Latino	51 Participants n=5 Participants • The ITT population included all participants randomized to treatment.	55 Participants n=20 Participants • The ITT population included all participants randomized to treatment.	106 Participants n=40 Participants • The ITT population included all participants randomized to treatment.
Ethnicity (NIH/OMB) Not Hispanic or Latino	571 Participants n=5 Participants • The ITT population included all participants randomized to treatment.	577 Participants n=20 Participants • The ITT population included all participants randomized to treatment.	1148 Participants n=40 Participants • The ITT population included all participants randomized to treatment.
Age, Continuous	38.8 years STANDARD_DEVIATION 15.83 • n=5 Participants • The ITT population included all participants randomized to treatment.	40.2 years STANDARD_DEVIATION 16.05 • n=20 Participants • The ITT population included all participants randomized to treatment.	39.5 years STANDARD_DEVIATION 15.95 • n=40 Participants • The ITT population included all participants randomized to treatment.
Sex: Female, Male Female	286 Participants n=5 Participants • The ITT population included all participants randomized to treatment.	272 Participants n=20 Participants • The ITT population included all participants randomized to treatment.	558 Participants n=40 Participants • The ITT population included all participants randomized to treatment.
Sex: Female, Male Male	378 Participants n=5 Participants • The ITT population included all participants randomized to treatment.	398 Participants n=20 Participants • The ITT population included all participants randomized to treatment.	776 Participants n=40 Participants • The ITT population included all participants randomized to treatment.
Ethnicity (NIH/OMB) Unknown or Not Reported	42 Participants n=5 Participants • The ITT population included all participants randomized to treatment.	38 Participants n=20 Participants • The ITT population included all participants randomized to treatment.	80 Participants n=40 Participants • The ITT population included all participants randomized to treatment.
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants • The ITT population included all participants randomized to treatment.	0 Participants n=20 Participants • The ITT population included all participants randomized to treatment.	0 Participants n=40 Participants • The ITT population included all participants randomized to treatment.
Race (NIH/OMB) Asian	56 Participants n=5 Participants • The ITT population included all participants randomized to treatment.	57 Participants n=20 Participants • The ITT population included all participants randomized to treatment.	113 Participants n=40 Participants • The ITT population included all participants randomized to treatment.
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants • The ITT population included all participants randomized to treatment.	0 Participants n=20 Participants • The ITT population included all participants randomized to treatment.	0 Participants n=40 Participants • The ITT population included all participants randomized to treatment.
Race (NIH/OMB) Black or African American	20 Participants n=5 Participants • The ITT population included all participants randomized to treatment.	25 Participants n=20 Participants • The ITT population included all participants randomized to treatment.	45 Participants n=40 Participants • The ITT population included all participants randomized to treatment.
Race (NIH/OMB) White	560 Participants n=5 Participants • The ITT population included all participants randomized to treatment.	554 Participants n=20 Participants • The ITT population included all participants randomized to treatment.	1114 Participants n=40 Participants • The ITT population included all participants randomized to treatment.
Race (NIH/OMB) More than one race	18 Participants n=5 Participants • The ITT population included all participants randomized to treatment.	17 Participants n=20 Participants • The ITT population included all participants randomized to treatment.	35 Participants n=40 Participants • The ITT population included all participants randomized to treatment.
Race (NIH/OMB) Unknown or Not Reported	10 Participants n=5 Participants • The ITT population included all participants randomized to treatment.	17 Participants n=20 Participants • The ITT population included all participants randomized to treatment.	27 Participants n=40 Participants • The ITT population included all participants randomized to treatment.

PRIMARY outcome

Timeframe: Baseline until PD or death or receipt of any subsequent anticancer therapy for HL after completion of frontline therapy (approximately up to 4 years)

Population: The ITT population included all participants randomized to treatment.

Outcome measures

Outcome measures
Measure	A+AVD n=664 Participants Brentuximab vedotin 1.2 milligram per kilogram (mg/kg), infusion, intravenously over 30-minutes plus doxorubicin 25 milligram per square meter (mg/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles. Brentuximab vedotin was administered within approximately 1 hour after completion of AVD.	ABVD n=670 Participants Doxorubicin 25 mg/m\^2, bleomycin 10 units per square meter (units/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles.
Modified Progression-free Survival (mPFS) Per Independent Review Facility (IRF)	NA months Interval 48.2 to Median and confidence interval was not estimable due to low number of participants with events.	NA months Median and confidence interval was not estimable due to low number of participants with events.

SECONDARY outcome

Timeframe: Baseline until death (approximately up to 4 years)

Population: The ITT population included all participants randomized to treatment.

OS was defined as the time from the date of randomization to the date of death. Participants without documented death at the time of analysis were censored at the date last known to be alive.

Outcome measures

Outcome measures
Measure	A+AVD n=664 Participants Brentuximab vedotin 1.2 milligram per kilogram (mg/kg), infusion, intravenously over 30-minutes plus doxorubicin 25 milligram per square meter (mg/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles. Brentuximab vedotin was administered within approximately 1 hour after completion of AVD.	ABVD n=670 Participants Doxorubicin 25 mg/m\^2, bleomycin 10 units per square meter (units/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles.
Overall Survival (OS)	NA months Median and confidence interval was not estimable due to low number of participants with events.	NA months Median and confidence interval was not estimable due to low number of participants with events.

SECONDARY outcome

Timeframe: Baseline up to end of randomized regimen (approximately 1 year)

Population: The ITT population included all participants randomized to treatment.

CR rate at the end of randomized regimen per investigator was defined as the percentage of participants who achieved CR at the end of treatment with randomized regimen (ABVD or A+AVD) as determined by IRF. CR was defined as disappearance of all evidence of disease.

Outcome measures

Outcome measures
Measure	A+AVD n=664 Participants Brentuximab vedotin 1.2 milligram per kilogram (mg/kg), infusion, intravenously over 30-minutes plus doxorubicin 25 milligram per square meter (mg/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles. Brentuximab vedotin was administered within approximately 1 hour after completion of AVD.	ABVD n=670 Participants Doxorubicin 25 mg/m\^2, bleomycin 10 units per square meter (units/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles.
Complete Remission (CR) Rate at the End of Randomized Regimen Per IRF	73 percentage of participants	70 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to 30 days after last dose of study drug (approximately 1 year)

Population: The safety population included all enrolled participants who received at least 1 dose of any study drug.

Outcome measures

Outcome measures
Measure	A+AVD n=662 Participants Brentuximab vedotin 1.2 milligram per kilogram (mg/kg), infusion, intravenously over 30-minutes plus doxorubicin 25 milligram per square meter (mg/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles. Brentuximab vedotin was administered within approximately 1 hour after completion of AVD.	ABVD n=659 Participants Doxorubicin 25 mg/m\^2, bleomycin 10 units per square meter (units/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles.
Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) TEAE	653 participants	646 participants
Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) SAE	284 participants	178 participants

SECONDARY outcome

Timeframe: Baseline up to 30 days after last dose of study drug (approximately 1 year)

Population: The safety population included all enrolled participants who received at least 1 dose of any study drug.

Outcome measures

Outcome measures
Measure	A+AVD n=662 Participants Brentuximab vedotin 1.2 milligram per kilogram (mg/kg), infusion, intravenously over 30-minutes plus doxorubicin 25 milligram per square meter (mg/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles. Brentuximab vedotin was administered within approximately 1 hour after completion of AVD.	ABVD n=659 Participants Doxorubicin 25 mg/m\^2, bleomycin 10 units per square meter (units/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles.
Number of Participants With Abnormal Clinical Laboratory Values	662 participants	658 participants

SECONDARY outcome

Timeframe: Baseline until PD or discontinuation of treatment or death, whichever occurs first (approximately up to 4 years)

Population: The ITT population included all participants randomized to treatment.

EFS was defined as the time from randomization until any cause of treatment failure: PD, premature discontinuation of randomized treatment for any reason, or death due to any cause, whichever occurs first. PD was defined as any new lesion or increase by \>=50% of previously involved sites from nadir per IRF.

Outcome measures

Outcome measures
Measure	A+AVD n=664 Participants Brentuximab vedotin 1.2 milligram per kilogram (mg/kg), infusion, intravenously over 30-minutes plus doxorubicin 25 milligram per square meter (mg/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles. Brentuximab vedotin was administered within approximately 1 hour after completion of AVD.	ABVD n=670 Participants Doxorubicin 25 mg/m\^2, bleomycin 10 units per square meter (units/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles.
Event-free Survival (EFS) Per IRF	NA months Interval 43.8 to Median and confidence interval was not estimable due to low number of participants with events.	NA months Median and confidence interval was not estimable due to low number of participants with events.

SECONDARY outcome

Timeframe: From CR until PD or death (approximately up to 4 years)

Population: The ITT included all participants randomized to treatment. The ITT population where participants achieved CR.

DFS per IRF was defined as the time from CR to disease progression as determined by an IRF or to death from lymphoma or acute toxicity from treatment. CR was defined as disappearance of all evidence of disease.

Outcome measures

Outcome measures
Measure	A+AVD n=543 Participants Brentuximab vedotin 1.2 milligram per kilogram (mg/kg), infusion, intravenously over 30-minutes plus doxorubicin 25 milligram per square meter (mg/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles. Brentuximab vedotin was administered within approximately 1 hour after completion of AVD.	ABVD n=528 Participants Doxorubicin 25 mg/m\^2, bleomycin 10 units per square meter (units/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles.
Disease-free Survival (DFS) Per IRF	NA months Interval 42.1 to Median and confidence interval was not estimable due to low number of participants with events.	NA months Median and confidence interval was not estimable due to low number of participants with events.

SECONDARY outcome

Timeframe: Baseline up to end of randomized regimen (approximately 1 year)

Population: The ITT population included all participants randomized to treatment.

ORR per IRF was defined as the percentage of participants who achieved CR or partial remission (PR) at the end of treatment with randomized regimen (ABVD or A+AVD) as determined by an IRF. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.

Outcome measures

Outcome measures
Measure	A+AVD n=664 Participants Brentuximab vedotin 1.2 milligram per kilogram (mg/kg), infusion, intravenously over 30-minutes plus doxorubicin 25 milligram per square meter (mg/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles. Brentuximab vedotin was administered within approximately 1 hour after completion of AVD.	ABVD n=670 Participants Doxorubicin 25 mg/m\^2, bleomycin 10 units per square meter (units/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles.
Overall Response Rate (ORR) Per IRF	86 percentage of participants	83 percentage of participants

SECONDARY outcome

Timeframe: From first documented response until PD (approximately 4 years)

Population: The ITT population included all participants randomized to treatment. The ITT population where participants achieved confirmed response of CR or PR.

DOR per IRF in participants with response was the time between first documentation of response (PR or CR) and PD as determined by an IRF. PD was defined as any new lesion or increase by \>=50% of previously involved sites from nadir. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.

Outcome measures

Outcome measures
Measure	A+AVD n=628 Participants Brentuximab vedotin 1.2 milligram per kilogram (mg/kg), infusion, intravenously over 30-minutes plus doxorubicin 25 milligram per square meter (mg/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles. Brentuximab vedotin was administered within approximately 1 hour after completion of AVD.	ABVD n=623 Participants Doxorubicin 25 mg/m\^2, bleomycin 10 units per square meter (units/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles.
Duration of Response (DOR) Per IRF	NA months Interval 42.1 to Median and confidence interval was not estimable due to low number of participants with events.	NA months Median and confidence interval was not estimable due to low number of participants with events.

SECONDARY outcome

Timeframe: From first documentation of CR until PD (approximately 4 years)

Population: The ITT population included all participants randomized to treatment. The ITT population where participants achieved CR.

DOCR per IRF in participants with CR was the time between first documentation of CR and PD as determined by an IRF. PD was defined as any new lesion or increase by \>=50% of previously involved sites from nadir. CR was defined as disappearance of all evidence of disease.

Outcome measures

Outcome measures
Measure	A+AVD n=543 Participants Brentuximab vedotin 1.2 milligram per kilogram (mg/kg), infusion, intravenously over 30-minutes plus doxorubicin 25 milligram per square meter (mg/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles. Brentuximab vedotin was administered within approximately 1 hour after completion of AVD.	ABVD n=528 Participants Doxorubicin 25 mg/m\^2, bleomycin 10 units per square meter (units/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles.
Duration of Complete Remission (DOCR) Per IRF	NA months Interval 42.1 to Median and confidence interval was not estimable due to low number of participants with events.	NA months Median and confidence interval was not estimable due to low number of participants with events.

SECONDARY outcome

Timeframe: Baseline up to end of frontline therapy (approximately 4 years)

Population: The ITT population included all participants randomized to treatment.

CR was defined as disappearance of all evidence of disease as determined by an IRF.

Outcome measures

Outcome measures
Measure	A+AVD n=664 Participants Brentuximab vedotin 1.2 milligram per kilogram (mg/kg), infusion, intravenously over 30-minutes plus doxorubicin 25 milligram per square meter (mg/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles. Brentuximab vedotin was administered within approximately 1 hour after completion of AVD.	ABVD n=670 Participants Doxorubicin 25 mg/m\^2, bleomycin 10 units per square meter (units/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles.
Percentage of Participants Not in CR Per IRF Who Received Subsequent Radiation After Completion of Frontline Therapy	8 percentage of participants	13 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to end of frontline therapy (approximately 4 years)

Population: The ITT population included all participants randomized to treatment.

CR rate at the end of frontline therapy per IRF was defined as the percentage of participants who achieved CR at the end of frontline therapy that is after completion of either randomized regimen or alternate frontline therapy as determined by an IRF. CR was defined as disappearance of all evidence of disease.

Outcome measures

Outcome measures
Measure	A+AVD n=664 Participants Brentuximab vedotin 1.2 milligram per kilogram (mg/kg), infusion, intravenously over 30-minutes plus doxorubicin 25 milligram per square meter (mg/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles. Brentuximab vedotin was administered within approximately 1 hour after completion of AVD.	ABVD n=670 Participants Doxorubicin 25 mg/m\^2, bleomycin 10 units per square meter (units/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles.
Complete Remission (CR) Per IRF Rate at the End of Frontline Therapy	73 percentage of participants	71 percentage of participants

SECONDARY outcome

Timeframe: Cycle 2 Day 25

Population: The ITT population included all participants randomized to treatment.

PET negativity rate at Cycle 2 was defined as the percentage of participants with negative Cycle 2 PET results defined as Deauville score less than or equal to (\<=) 3 at Cycle 2. The Deauville score according to IRF assessment of response was used to evaluate the results of PET scans.

Outcome measures

Outcome measures
Measure	A+AVD n=664 Participants Brentuximab vedotin 1.2 milligram per kilogram (mg/kg), infusion, intravenously over 30-minutes plus doxorubicin 25 milligram per square meter (mg/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles. Brentuximab vedotin was administered within approximately 1 hour after completion of AVD.	ABVD n=670 Participants Doxorubicin 25 mg/m\^2, bleomycin 10 units per square meter (units/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles.
Positron Emission Tomography (PET) Negativity Rate Per IRF at Cycle 2	89 percentage of participants	86 percentage of participants

SECONDARY outcome

Timeframe: Cycle 1 Day 1 and Cycle 3 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose

Population: The pharmacokinetic (PK) population included enrolled participants with sufficient dosing and PK data to reliably estimate PK parameters as determined by a clinical pharmacologist. The intensive PK (iPK) population was the subset of PK population. The iPK population where data at specified timepoints was available.

Outcome measures

Outcome measures
Measure	A+AVD n=59 Participants Brentuximab vedotin 1.2 milligram per kilogram (mg/kg), infusion, intravenously over 30-minutes plus doxorubicin 25 milligram per square meter (mg/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles. Brentuximab vedotin was administered within approximately 1 hour after completion of AVD.	ABVD Doxorubicin 25 mg/m\^2, bleomycin 10 units per square meter (units/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles.
A+AVD: Cmax: Maximum Observed Serum Concentration for Brentuximab Vedotin Antibody-drug Conjugate (ADC) and Total Antibody (TAb) Cycle 1 Day 1: ADC	22.9 microgram per milliliter (microgm/mL) Standard Deviation 6.72	—
A+AVD: Cmax: Maximum Observed Serum Concentration for Brentuximab Vedotin Antibody-drug Conjugate (ADC) and Total Antibody (TAb) Cycle 3 Day 1: ADC	23.6 microgram per milliliter (microgm/mL) Standard Deviation 6.81	—
A+AVD: Cmax: Maximum Observed Serum Concentration for Brentuximab Vedotin Antibody-drug Conjugate (ADC) and Total Antibody (TAb) Cycle 1 Day 1: TAb	22.6 microgram per milliliter (microgm/mL) Standard Deviation 5.48	—
A+AVD: Cmax: Maximum Observed Serum Concentration for Brentuximab Vedotin Antibody-drug Conjugate (ADC) and Total Antibody (TAb) Cycle 3 Day 1: TAb	26.4 microgram per milliliter (microgm/mL) Standard Deviation 6.11	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1 and Cycle 3 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose

Population: The PK population included enrolled participants with sufficient dosing and PK data to reliably estimate PK parameters as determined by a clinical pharmacologist. The iPK population was the subset of PK population. The iPK population where data at specified timepoints was available.

Outcome measures

Outcome measures
Measure	A+AVD n=59 Participants Brentuximab vedotin 1.2 milligram per kilogram (mg/kg), infusion, intravenously over 30-minutes plus doxorubicin 25 milligram per square meter (mg/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles. Brentuximab vedotin was administered within approximately 1 hour after completion of AVD.	ABVD Doxorubicin 25 mg/m\^2, bleomycin 10 units per square meter (units/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles.
A+AVD: Cmax: Maximum Observed Plasma Concentration for Brentuximab Vedotin Monomethyl Auristatin E (MMAE) Cycle 1 Day 1	3.20 nanogram per milliliter (ng/mL) Standard Deviation 2.99	—
A+AVD: Cmax: Maximum Observed Plasma Concentration for Brentuximab Vedotin Monomethyl Auristatin E (MMAE) Cycle 3 Day 1	1.36 nanogram per milliliter (ng/mL) Standard Deviation 0.790	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose

Outcome measures

Outcome measures
Measure	A+AVD n=59 Participants Brentuximab vedotin 1.2 milligram per kilogram (mg/kg), infusion, intravenously over 30-minutes plus doxorubicin 25 milligram per square meter (mg/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles. Brentuximab vedotin was administered within approximately 1 hour after completion of AVD.	ABVD Doxorubicin 25 mg/m\^2, bleomycin 10 units per square meter (units/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles.
A+AVD: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin ADC and TAb Cycle 1 Day 1: ADC	47.4 daymicrogram per milliliter (dayug/mL) Standard Deviation 12.0	—
A+AVD: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin ADC and TAb Cycle 1 Day 1: TAb	93.0 daymicrogram per milliliter (dayug/mL) Standard Deviation 25.7	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose

Outcome measures

Outcome measures
Measure	A+AVD n=59 Participants Brentuximab vedotin 1.2 milligram per kilogram (mg/kg), infusion, intravenously over 30-minutes plus doxorubicin 25 milligram per square meter (mg/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles. Brentuximab vedotin was administered within approximately 1 hour after completion of AVD.	ABVD Doxorubicin 25 mg/m\^2, bleomycin 10 units per square meter (units/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles.
A+AVD: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin MMAE	25.3 daynanogram per milliliter (dayng/mL) Standard Deviation 19.2	—

SECONDARY outcome

Timeframe: Baseline up to end of treatment (approximately 1 year)

Population: The safety population included all enrolled participants who received at least 1 dose of any study drug. The safety population-immunogenicity-evaluable participants where baseline and at least one postbaseline sample was available.

The nATA positive was defined as positive ATA with neutralizing activity at any postbaseline visit.

Outcome measures

Outcome measures
Measure	A+AVD n=632 Participants Brentuximab vedotin 1.2 milligram per kilogram (mg/kg), infusion, intravenously over 30-minutes plus doxorubicin 25 milligram per square meter (mg/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles. Brentuximab vedotin was administered within approximately 1 hour after completion of AVD.	ABVD Doxorubicin 25 mg/m\^2, bleomycin 10 units per square meter (units/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles.
A+AVD: Number of Participants With Antitherapeutic Antibody (ATA) and Neutralizing Antitherapeutic Antibody (nATA) Positive for Brentuximab Vedotin ATA positive	109 participants	—
A+AVD: Number of Participants With Antitherapeutic Antibody (ATA) and Neutralizing Antitherapeutic Antibody (nATA) Positive for Brentuximab Vedotin nATA positive	12 participants	—

SECONDARY outcome

Timeframe: Baseline up to end of treatment (approximately 1 year)

Population: The ITT population included all participants randomized to treatment.

EORTC QLQ-C30 included 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) and global health status/QOL scale. It has 28 questions (4-point scale where 1=not at all \[best\] to 4=Very Much \[worst\]) and 2 questions (7-point scale where 1=very poor \[worst\] to 7= excellent \[best\]). Raw scores were converted into scale scores from 0 to 100. For functional scales and global health status/QOL scale, higher scores show better QOL; for symptom scales, lower scores show better QOL. mPFS was time from date of randomization to date of first of documentation of PD, death due to any cause, or for participants who were confirmed non complete responders per IRF, receipt of subsequent anticancer therapy for HL after completion of frontline therapy. PD is any new lesion or increase by \>=50% of previously involved sites from nadir.

Outcome measures

Outcome measures
Measure	A+AVD n=664 Participants Brentuximab vedotin 1.2 milligram per kilogram (mg/kg), infusion, intravenously over 30-minutes plus doxorubicin 25 milligram per square meter (mg/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles. Brentuximab vedotin was administered within approximately 1 hour after completion of AVD.	ABVD n=670 Participants Doxorubicin 25 mg/m\^2, bleomycin 10 units per square meter (units/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles.
Change From Baseline in Patient-Reported Outcome (PRO) Scores by mPFS Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) at EOT Baseline: With mPFS event	78.15 units on scale Standard Deviation 16.527	76.68 units on scale Standard Deviation 18.661
Change From Baseline in Patient-Reported Outcome (PRO) Scores by mPFS Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) at EOT Without mPFS event	79.85 units on scale Standard Deviation 16.648	79.91 units on scale Standard Deviation 16.218
Change From Baseline in Patient-Reported Outcome (PRO) Scores by mPFS Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) at EOT Change at end of treatment: with mPFS event	2.68 units on scale Standard Deviation 15.434	8.58 units on scale Standard Deviation 17.848
Change From Baseline in Patient-Reported Outcome (PRO) Scores by mPFS Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) at EOT Change at end of treatment: without mPFS event	3.35 units on scale Standard Deviation 17.417	6.08 units on scale Standard Deviation 16.141

Adverse Events

A+AVD

Serious events: 284 serious events

Other events: 644 other events

Deaths: 9 deaths

ABVD

Serious events: 178 serious events

Other events: 632 other events

Deaths: 13 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
Publication restrictions are in place

Restriction type: OTHER