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A Frontline Therapy Trial in Participants With Advanced Classical Hodgkin Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01712490
Recruitment Status : Active, not recruiting
First Posted : October 23, 2012
Results First Posted : November 27, 2018
Last Update Posted : February 20, 2024
Sponsor:
Collaborator:
Seagen Inc.
Information provided by (Responsible Party):
Takeda

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hodgkin Lymphoma
Interventions Drug: brentuximab vedotin
Drug: doxorubicin
Drug: bleomycin
Drug: vinblastine
Drug: dacarbazine
Enrollment 1334
Recruitment Details 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.
Pre-assignment Details 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).
Arm/Group Title A+AVD ABVD
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 664 670
Treated 662 659
Completed 0 0
Not Completed 664 670
Reason Not Completed
Ongoing             601             586
Other             11             11
Withdrawal by Subject             36             44
Lost to Follow-up             16             29
Arm/Group Title A+AVD ABVD Total
Hide Arm/Group Description 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. 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 of all reporting groups
Overall Number of Baseline Participants 664 670 1334
Hide Baseline Analysis Population Description
The intent-to-treat (ITT) population included all participants randomized to treatment.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 664 participants 670 participants 1334 participants
38.8  (15.83) 40.2  (16.05) 39.5  (15.95)
[1]
Measure Analysis Population Description: The ITT population included all participants randomized to treatment.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 664 participants 670 participants 1334 participants
Female
286
  43.1%
272
  40.6%
558
  41.8%
Male
378
  56.9%
398
  59.4%
776
  58.2%
[1]
Measure Analysis Population Description: The ITT population included all participants randomized to treatment.
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 664 participants 670 participants 1334 participants
Hispanic or Latino
51
   7.7%
55
   8.2%
106
   7.9%
Not Hispanic or Latino
571
  86.0%
577
  86.1%
1148
  86.1%
Unknown or Not Reported
42
   6.3%
38
   5.7%
80
   6.0%
[1]
Measure Analysis Population Description: The ITT population included all participants randomized to treatment.
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 664 participants 670 participants 1334 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
56
   8.4%
57
   8.5%
113
   8.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
20
   3.0%
25
   3.7%
45
   3.4%
White
560
  84.3%
554
  82.7%
1114
  83.5%
More than one race
18
   2.7%
17
   2.5%
35
   2.6%
Unknown or Not Reported
10
   1.5%
17
   2.5%
27
   2.0%
[1]
Measure Analysis Population Description: The ITT population included all participants randomized to treatment.
1.Primary Outcome
Title Modified Progression-free Survival (mPFS) Per Independent Review Facility (IRF)
Hide Description 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.
Time Frame Baseline until PD or death or receipt of any subsequent anticancer therapy for HL after completion of frontline therapy (approximately up to 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants randomized to treatment.
Arm/Group Title A+AVD ABVD
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 664 670
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(48.2 to NA)
NA [1] 
(NA to NA)
[1]
Median and confidence interval was not estimable due to low number of participants with events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection A+AVD, ABVD
Comments Hazard ratio (A+AVD/ABVD) and 95% confidence interval (CI) are based on a stratified Cox's proportional hazard regression model with stratification factors region and number of International Prognostic Factor Project (IPFP) risk factors at baseline with treatment as the explanatory variable in the model. Hazard ratio less than (<) 1 favors A+AVD arm.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.035
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.770
Confidence Interval (2-Sided) 95%
0.603 to 0.983
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Overall Survival (OS)
Hide Description 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.
Time Frame Baseline until death (approximately up to 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants randomized to treatment.
Arm/Group Title A+AVD ABVD
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 664 670
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Median and confidence interval was not estimable due to low number of participants with events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection A+AVD, ABVD
Comments Hazard ratio (A+AVD/ABVD) and 95% CI are based on a stratified Cox's proportional hazard regression model with stratification factors region and number of IPFP risk factors at baseline with treatment as the explanatory variable in the model. Hazard ratio <1 favors A+AVD arm.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.199
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.728
Confidence Interval (2-Sided) 95%
0.448 to 1.184
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Complete Remission (CR) Rate at the End of Randomized Regimen Per IRF
Hide Description 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.
Time Frame Baseline up to end of randomized regimen (approximately 1 year)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants randomized to treatment.
Arm/Group Title A+AVD ABVD
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 664 670
Measure Type: Number
Unit of Measure: percentage of participants
73 70
4.Secondary Outcome
Title Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
Hide Description [Not Specified]
Time Frame Baseline up to 30 days after last dose of study drug (approximately 1 year)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all enrolled participants who received at least 1 dose of any study drug.
Arm/Group Title A+AVD ABVD
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 662 659
Measure Type: Number
Unit of Measure: participants
TEAE 653 646
SAE 284 178
5.Secondary Outcome
Title Number of Participants With Abnormal Clinical Laboratory Values
Hide Description [Not Specified]
Time Frame Baseline up to 30 days after last dose of study drug (approximately 1 year)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all enrolled participants who received at least 1 dose of any study drug.
Arm/Group Title A+AVD ABVD
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 662 659
Measure Type: Number
Unit of Measure: participants
662 658
6.Secondary Outcome
Title Event-free Survival (EFS) Per IRF
Hide Description 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.
Time Frame Baseline until PD or discontinuation of treatment or death, whichever occurs first (approximately up to 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants randomized to treatment.
Arm/Group Title A+AVD ABVD
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 664 670
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(43.8 to NA)
NA [1] 
(NA to NA)
[1]
Median and confidence interval was not estimable due to low number of participants with events.
7.Secondary Outcome
Title Disease-free Survival (DFS) Per IRF
Hide Description 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.
Time Frame From CR until PD or death (approximately up to 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT included all participants randomized to treatment. The ITT population where participants achieved CR.
Arm/Group Title A+AVD ABVD
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 543 528
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(42.1 to NA)
NA [1] 
(NA to NA)
[1]
Median and confidence interval was not estimable due to low number of participants with events.
8.Secondary Outcome
Title Overall Response Rate (ORR) Per IRF
Hide Description 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.
Time Frame Baseline up to end of randomized regimen (approximately 1 year)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants randomized to treatment.
Arm/Group Title A+AVD ABVD
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 664 670
Measure Type: Number
Unit of Measure: percentage of participants
86 83
9.Secondary Outcome
Title Duration of Response (DOR) Per IRF
Hide Description 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.
Time Frame From first documented response until PD (approximately 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants randomized to treatment. The ITT population where participants achieved confirmed response of CR or PR.
Arm/Group Title A+AVD ABVD
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 628 623
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(42.1 to NA)
NA [1] 
(NA to NA)
[1]
Median and confidence interval was not estimable due to low number of participants with events.
10.Secondary Outcome
Title Duration of Complete Remission (DOCR) Per IRF
Hide Description 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.
Time Frame From first documentation of CR until PD (approximately 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants randomized to treatment. The ITT population where participants achieved CR.
Arm/Group Title A+AVD ABVD
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 543 528
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(42.1 to NA)
NA [1] 
(NA to NA)
[1]
Median and confidence interval was not estimable due to low number of participants with events.
11.Secondary Outcome
Title Percentage of Participants Not in CR Per IRF Who Received Subsequent Radiation After Completion of Frontline Therapy
Hide Description CR was defined as disappearance of all evidence of disease as determined by an IRF.
Time Frame Baseline up to end of frontline therapy (approximately 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants randomized to treatment.
Arm/Group Title A+AVD ABVD
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 664 670
Measure Type: Number
Unit of Measure: percentage of participants
8 13
12.Secondary Outcome
Title Complete Remission (CR) Per IRF Rate at the End of Frontline Therapy
Hide Description 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.
Time Frame Baseline up to end of frontline therapy (approximately 4 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants randomized to treatment.
Arm/Group Title A+AVD ABVD
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 664 670
Measure Type: Number
Unit of Measure: percentage of participants
73 71
13.Secondary Outcome
Title Positron Emission Tomography (PET) Negativity Rate Per IRF at Cycle 2
Hide Description 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.
Time Frame Cycle 2 Day 25
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants randomized to treatment.
Arm/Group Title A+AVD ABVD
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 664 670
Measure Type: Number
Unit of Measure: percentage of participants
89 86
14.Secondary Outcome
Title A+AVD: Cmax: Maximum Observed Serum Concentration for Brentuximab Vedotin Antibody-drug Conjugate (ADC) and Total Antibody (TAb)
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 and Cycle 3 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title A+AVD
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 59
Geometric Mean (Standard Deviation)
Unit of Measure: microgram per milliliter (microgm/mL)
Cycle 1 Day 1: ADC Number Analyzed 55 participants
22.9  (6.72)
Cycle 3 Day 1: ADC Number Analyzed 52 participants
23.6  (6.81)
Cycle 1 Day 1: TAb Number Analyzed 55 participants
22.6  (5.48)
Cycle 3 Day 1: TAb Number Analyzed 52 participants
26.4  (6.11)
15.Secondary Outcome
Title A+AVD: Cmax: Maximum Observed Plasma Concentration for Brentuximab Vedotin Monomethyl Auristatin E (MMAE)
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1 and Cycle 3 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title A+AVD
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 59
Geometric Mean (Standard Deviation)
Unit of Measure: nanogram per milliliter (ng/mL)
Cycle 1 Day 1 Number Analyzed 59 participants
3.20  (2.99)
Cycle 3 Day 1 Number Analyzed 56 participants
1.36  (0.790)
16.Secondary Outcome
Title A+AVD: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin ADC and TAb
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose
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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.
Arm/Group Title A+AVD
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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.
Overall Number of Participants Analyzed 59
Mean (Standard Deviation)
Unit of Measure: day*microgram per milliliter (day*ug/mL)
Cycle 1 Day 1: ADC Number Analyzed 53 participants
47.4  (12.0)
Cycle 1 Day 1: TAb Number Analyzed 51 participants
93.0  (25.7)
17.Secondary Outcome
Title A+AVD: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin MMAE
Hide Description [Not Specified]
Time Frame Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose
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Hide Analysis Population Description
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.
Arm/Group Title A+AVD
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 59
Mean (Standard Deviation)
Unit of Measure: day*nanogram per milliliter (day*ng/mL)
25.3  (19.2)
18.Secondary Outcome
Title A+AVD: Number of Participants With Antitherapeutic Antibody (ATA) and Neutralizing Antitherapeutic Antibody (nATA) Positive for Brentuximab Vedotin
Hide Description The nATA positive was defined as positive ATA with neutralizing activity at any postbaseline visit.
Time Frame Baseline up to end of treatment (approximately 1 year)
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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.
Arm/Group Title A+AVD
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 632
Measure Type: Number
Unit of Measure: participants
ATA positive 109
nATA positive 12
19.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Baseline up to end of treatment (approximately 1 year)
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Hide Analysis Population Description
The ITT population included all participants randomized to treatment.
Arm/Group Title A+AVD ABVD
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 664 670
Mean (Standard Deviation)
Unit of Measure: units on scale
Baseline: With mPFS event Number Analyzed 115 participants 143 participants
78.15  (16.527) 76.68  (18.661)
Without mPFS event Number Analyzed 533 participants 508 participants
79.85  (16.648) 79.91  (16.218)
Change at end of treatment: with mPFS event Number Analyzed 91 participants 112 participants
2.68  (15.434) 8.58  (17.848)
Change at end of treatment: without mPFS event Number Analyzed 475 participants 452 participants
3.35  (17.417) 6.08  (16.141)
Time Frame TEAEs are adverse events that started after the first dose of study drug and no more than 30 days (approximately 1 year) for a serious adverse event after the last dose of study drug
Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. The safety population included all enrolled participants who received at least 1 dose of any study drug.
 
Arm/Group Title A+AVD ABVD
Hide Arm/Group Description 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. 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.
All-Cause Mortality
A+AVD ABVD
Affected / at Risk (%) Affected / at Risk (%)
Total   9/662 (1.36%)      13/659 (1.97%)    
Hide Serious Adverse Events
A+AVD ABVD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   284/662 (42.90%)      178/659 (27.01%)    
Blood and lymphatic system disorders     
Febrile neutropenia † 1  114/662 (17.22%)  151 43/659 (6.53%)  52
Neutropenia † 1  19/662 (2.87%)  30 4/659 (0.61%)  5
Anaemia † 1  7/662 (1.06%)  10 3/659 (0.46%)  3
Lymphadenitis † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Lymphadenopathy mediastinal † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Pancytopenia † 1  2/662 (0.30%)  2 0/659 (0.00%)  0
Thrombocytopenia † 1  1/662 (0.15%)  1 1/659 (0.15%)  1
Histiocytosis haematophagic † 1  1/662 (0.15%)  2 0/659 (0.00%)  0
Cardiac disorders     
Myocardial infarction † 1  3/662 (0.45%)  3 1/659 (0.15%)  1
Acute myocardial infarction † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Angina pectoris † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Microvascular coronary artery disease † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Supraventricular tachycardia † 1  2/662 (0.30%)  2 1/659 (0.15%)  1
Atrial fibrillation † 1  2/662 (0.30%)  2 0/659 (0.00%)  0
Sinus tachycardia † 1  1/662 (0.15%)  1 1/659 (0.15%)  1
Tachycardia † 1  2/662 (0.30%)  3 1/659 (0.15%)  1
Cardiac arrest † 1  0/662 (0.00%)  0 2/659 (0.30%)  2
Cardio-respiratory arrest † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Cardiac failure † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Cardiopulmonary failure † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Pericarditis † 1  1/662 (0.15%)  1 1/659 (0.15%)  1
Atrial thrombosis † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Congenital, familial and genetic disorders     
Branchial cyst † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Endocrine disorders     
Cushing's syndrome † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Eye disorders     
Vision blurred † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Gastrointestinal disorders     
Abdominal pain † 1  14/662 (2.11%)  15 4/659 (0.61%)  4
Abdominal pain lower † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Vomiting † 1  11/662 (1.66%)  11 3/659 (0.46%)  3
Nausea † 1  7/662 (1.06%)  7 3/659 (0.46%)  3
Constipation † 1  11/662 (1.66%)  12 6/659 (0.91%)  7
Diarrhoea † 1  11/662 (1.66%)  13 1/659 (0.15%)  1
Colitis † 1  4/662 (0.60%)  4 0/659 (0.00%)  0
Neutropenic colitis † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Gastritis † 1  2/662 (0.30%)  2 3/659 (0.46%)  4
Ileus † 1  3/662 (0.45%)  3 1/659 (0.15%)  1
Ileus paralytic † 1  4/662 (0.60%)  5 0/659 (0.00%)  0
Pancreatitis † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Pancreatitis acute † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Enterocolitis † 1  1/662 (0.15%)  1 1/659 (0.15%)  1
Mouth ulceration † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Stomatitis † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Anal ulcer † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Gastrointestinal disorder † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Haemorrhoids † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
General disorders     
Pyrexia † 1  44/662 (6.65%)  55 28/659 (4.25%)  32
Non-cardiac chest pain † 1  1/662 (0.15%)  1 2/659 (0.30%)  3
Pain † 1  1/662 (0.15%)  2 1/659 (0.15%)  2
Chest pain † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Fatigue † 1  2/662 (0.30%)  2 0/659 (0.00%)  0
Asthenia † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Malaise † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Multiple organ dysfunction syndrome † 1  1/662 (0.15%)  1 1/659 (0.15%)  1
Influenza like illness † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Peripheral swelling † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Chills † 1  1/662 (0.15%)  1 2/659 (0.30%)  2
Death † 1  1/662 (0.15%)  1 1/659 (0.15%)  1
Catheter site haemorrhage † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Catheter site pain † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Infusion site extravasation † 1  1/662 (0.15%)  1 1/659 (0.15%)  1
Complication associated with device † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Oedema peripheral † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Adverse drug reaction † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Device related thrombosis † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Hepatobiliary disorders     
Cholecystitis acute † 1  1/662 (0.15%)  1 1/659 (0.15%)  1
Cholelithiasis † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Hepatotoxicity † 1  2/662 (0.30%)  2 0/659 (0.00%)  0
Gallbladder obstruction † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Liver disorder † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Hepatic function abnormal † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Hepatic failure † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Immune system disorders     
Drug hypersensitivity † 1  1/662 (0.15%)  1 1/659 (0.15%)  1
Infections and infestations     
Pneumonia † 1  18/662 (2.72%)  19 15/659 (2.28%)  18
Lung infection † 1  4/662 (0.60%)  4 2/659 (0.30%)  2
Lower respiratory tract infection † 1  2/662 (0.30%)  2 3/659 (0.46%)  3
Bronchitis † 1  1/662 (0.15%)  1 2/659 (0.30%)  2
Atypical pneumonia † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Sepsis † 1  14/662 (2.11%)  15 4/659 (0.61%)  4
Neutropenic sepsis † 1  8/662 (1.21%)  10 2/659 (0.30%)  2
Bacteraemia † 1  1/662 (0.15%)  1 4/659 (0.61%)  4
Septic shock † 1  4/662 (0.60%)  6 0/659 (0.00%)  0
Septic embolus † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Device related infection † 1  7/662 (1.06%)  8 2/659 (0.30%)  2
Respiratory tract infection † 1  1/662 (0.15%)  1 2/659 (0.30%)  2
Infection † 1  1/662 (0.15%)  1 1/659 (0.15%)  1
Catheter site infection † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Lymph gland infection † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Pelvic infection † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Wound infection † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Upper respiratory tract infection † 1  3/662 (0.45%)  3 2/659 (0.30%)  2
Tonsillitis † 1  1/662 (0.15%)  1 1/659 (0.15%)  1
Laryngitis † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Pharyngeal abscess † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Pharyngitis † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Sinusitis † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Cellulitis † 1  5/662 (0.76%)  5 2/659 (0.30%)  2
Bacterial infection † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Cellulitis orbital † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Gangrene † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Pneumocystis jirovecii pneumonia † 1  5/662 (0.76%)  5 2/659 (0.30%)  3
Pneumocystis jirovecii infection † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Anal abscess † 1  2/662 (0.30%)  2 0/659 (0.00%)  0
Abdominal abscess † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Appendicitis † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Diverticulitis † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Enteritis infectious † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Skin infection † 1  2/662 (0.30%)  3 1/659 (0.15%)  1
Subcutaneous abscess † 1  1/662 (0.15%)  1 1/659 (0.15%)  1
Folliculitis † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Gastroenteritis viral † 1  1/662 (0.15%)  1 2/659 (0.30%)  2
Pneumonia viral † 1  2/662 (0.30%)  2 0/659 (0.00%)  0
Viral infection † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Clostridium difficile colitis † 1  2/662 (0.30%)  2 1/659 (0.15%)  1
Clostridium difficile infection † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Tooth abscess † 1  2/662 (0.30%)  2 0/659 (0.00%)  0
Pericoronitis † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Periodontitis † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Staphylococcal infection † 1  1/662 (0.15%)  1 1/659 (0.15%)  1
Staphylococcal bacteraemia † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Staphylococcal sepsis † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Urinary tract infection † 1  2/662 (0.30%)  2 1/659 (0.15%)  1
Pyelonephritis † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Soft tissue infection † 1  1/662 (0.15%)  1 2/659 (0.30%)  2
Aspergillus infection † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Bronchopulmonary aspergillosis † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Genital infection female † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Vulvitis † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Fungal sepsis † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Pneumonia fungal † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Herpes virus infection † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Herpes zoster † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Ophthalmic herpes zoster † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Infected lymphocele † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Phlebitis infective † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Endocarditis † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Encephalitis † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Flavivirus infection † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Hepatitis B † 1  0/662 (0.00%)  0 1/659 (0.15%)  2
Influenza † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Moraxella infection † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Parainfluenzae virus infection † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Pneumonia streptococcal † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Injury, poisoning and procedural complications     
Hip fracture † 1  2/662 (0.30%)  2 0/659 (0.00%)  0
Ankle fracture † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Femur fracture † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Infusion related reaction † 1  1/662 (0.15%)  1 1/659 (0.15%)  1
Fall † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Investigations     
Neutrophil count decreased † 1  3/662 (0.45%)  3 1/659 (0.15%)  1
Pseudomonas test positive † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Staphylococcus test positive † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Blood glucose increased † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Amylase increased † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Lipase increased † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Electrocardiogram QT prolonged † 1  1/662 (0.15%)  2 0/659 (0.00%)  0
Blood bilirubin increased † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Body temperature increased † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Metabolism and nutrition disorders     
Dehydration † 1  10/662 (1.51%)  10 3/659 (0.46%)  3
Hyponatraemia † 1  4/662 (0.60%)  4 3/659 (0.46%)  3
Hyperglycaemia † 1  3/662 (0.45%)  4 1/659 (0.15%)  1
Hypokalaemia † 1  2/662 (0.30%)  2 1/659 (0.15%)  1
Hyperkalaemia † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Failure to thrive † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Malnutrition † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Hypomagnesaemia † 1  2/662 (0.30%)  2 0/659 (0.00%)  0
Type 2 diabetes mellitus † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Hypophosphataemia † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Pain in extremity † 1  2/662 (0.30%)  2 1/659 (0.15%)  1
Back pain † 1  2/662 (0.30%)  2 0/659 (0.00%)  0
Flank pain † 1  2/662 (0.30%)  2 0/659 (0.00%)  0
Musculoskeletal pain † 1  1/662 (0.15%)  2 0/659 (0.00%)  0
Myalgia † 1  1/662 (0.15%)  1 1/659 (0.15%)  1
Bone pain † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Arthralgia † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Muscular weakness † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Neuroendocrine tumour † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Pituitary tumour † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
T-cell lymphoma † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Bile duct cancer † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Gastrointestinal stromal tumour † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Benign ovarian tumour † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Plasma cell myeloma † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Nervous system disorders     
Syncope † 1  2/662 (0.30%)  3 2/659 (0.30%)  2
Lethargy † 1  2/662 (0.30%)  2 1/659 (0.15%)  1
Somnolence † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Headache † 1  3/662 (0.45%)  3 3/659 (0.46%)  3
Peripheral motor neuropathy † 1  3/662 (0.45%)  3 0/659 (0.00%)  0
Peripheral sensory neuropathy † 1  2/662 (0.30%)  2 0/659 (0.00%)  0
Polyneuropathy † 1  1/662 (0.15%)  1 1/659 (0.15%)  1
Cerebrovascular accident † 1  1/662 (0.15%)  1 1/659 (0.15%)  1
Lacunar infarction † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Autonomic neuropathy † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Facial paralysis † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Hypoaesthesia † 1  1/662 (0.15%)  3 0/659 (0.00%)  0
Hemiparesis † 1  1/662 (0.15%)  3 0/659 (0.00%)  0
Neuralgia † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Spinal cord ischaemia † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Psychiatric disorders     
Anxiety † 1  2/662 (0.30%)  2 1/659 (0.15%)  2
Agitation † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Delirium † 1  2/662 (0.30%)  2 0/659 (0.00%)  0
Schizoaffective disorder bipolar type † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Suicidal ideation † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Renal and urinary disorders     
Acute kidney injury † 1  3/662 (0.45%)  3 0/659 (0.00%)  0
Anuria † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Ureteric obstruction † 1  1/662 (0.15%)  1 1/659 (0.15%)  1
Haematuria † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Reproductive system and breast disorders     
Metrorrhagia † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Vaginal haemorrhage † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism † 1  11/662 (1.66%)  11 9/659 (1.37%)  9
Pulmonary thrombosis † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Pneumonitis † 1  2/662 (0.30%)  2 12/659 (1.82%)  13
Pulmonary toxicity † 1  0/662 (0.00%)  0 5/659 (0.76%)  6
Interstitial lung disease † 1  1/662 (0.15%)  1 2/659 (0.30%)  2
Lung infiltration † 1  2/662 (0.30%)  2 0/659 (0.00%)  0
Organising pneumonia † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Dyspnoea † 1  3/662 (0.45%)  3 5/659 (0.76%)  5
Respiratory failure † 1  2/662 (0.30%)  3 4/659 (0.61%)  4
Hypoxia † 1  1/662 (0.15%)  1 2/659 (0.30%)  2
Cough † 1  1/662 (0.15%)  1 1/659 (0.15%)  1
Acute pulmonary oedema † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Acute respiratory distress syndrome † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Lung disorder † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Respiratory disorder † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Chronic obstructive pulmonary disease † 1  1/662 (0.15%)  2 0/659 (0.00%)  0
Stridor † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Pleuritic pain † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Pleurisy † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Pneumothorax † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Skin and subcutaneous tissue disorders     
Rash macular † 1  1/662 (0.15%)  4 0/659 (0.00%)  0
Rash maculo-papular † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Hidradenitis † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Drug eruption † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Skin ulcer † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Vascular disorders     
Deep vein thrombosis † 1  5/662 (0.76%)  5 2/659 (0.30%)  3
Thrombophlebitis superficial † 1  1/662 (0.15%)  1 1/659 (0.15%)  1
Jugular vein thrombosis † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Pelvic venous thrombosis † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Peripheral artery thrombosis † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Venous thrombosis limb † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Hypotension † 1  4/662 (0.60%)  4 1/659 (0.15%)  1
Orthostatic hypotension † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Embolism † 1  0/662 (0.00%)  0 4/659 (0.61%)  4
Venous thrombosis † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Brachiocephalic vein occlusion † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
Superior vena cava syndrome † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Phlebitis † 1  1/662 (0.15%)  1 0/659 (0.00%)  0
Vena cava thrombosis † 1  0/662 (0.00%)  0 1/659 (0.15%)  1
1
Term from vocabulary, MedDRA (19.0)
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
A+AVD ABVD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   644/662 (97.28%)      632/659 (95.90%)    
Blood and lymphatic system disorders     
Neutropenia † 1  374/662 (56.50%)  1169 291/659 (44.16%)  813
Anaemia † 1  136/662 (20.54%)  237 65/659 (9.86%)  97
Leukopenia † 1  42/662 (6.34%)  124 37/659 (5.61%)  118
Gastrointestinal disorders     
Nausea † 1  346/662 (52.27%)  673 369/659 (55.99%)  735
Constipation † 1  273/662 (41.24%)  361 239/659 (36.27%)  336
Vomiting † 1  212/662 (32.02%)  342 183/659 (27.77%)  284
Diarrhoea † 1  176/662 (26.59%)  231 121/659 (18.36%)  155
Stomatitis † 1  138/662 (20.85%)  182 104/659 (15.78%)  135
Abdominal pain † 1  135/662 (20.39%)  185 65/659 (9.86%)  79
Dyspepsia † 1  84/662 (12.69%)  100 75/659 (11.38%)  93
Abdominal pain upper † 1  64/662 (9.67%)  74 34/659 (5.16%)  37
Gastrooesophageal reflux disease † 1  33/662 (4.98%)  36 47/659 (7.13%)  49
General disorders     
Fatigue † 1  209/662 (31.57%)  272 211/659 (32.02%)  293
Pyrexia † 1  149/662 (22.51%)  224 128/659 (19.42%)  191
Asthenia † 1  65/662 (9.82%)  97 42/659 (6.37%)  66
Chills † 1  37/662 (5.59%)  52 46/659 (6.98%)  51
Non-cardiac chest pain † 1  37/662 (5.59%)  40 45/659 (6.83%)  53
Infections and infestations     
Upper respiratory tract infection † 1  68/662 (10.27%)  76 69/659 (10.47%)  75
Nasopharyngitis † 1  28/662 (4.23%)  39 35/659 (5.31%)  40
Investigations     
Weight decreased † 1  148/662 (22.36%)  168 40/659 (6.07%)  46
Neutrophil count decreased † 1  86/662 (12.99%)  285 78/659 (11.84%)  191
Alanine aminotransferase increased † 1  68/662 (10.27%)  92 26/659 (3.95%)  28
White blood cell count decreased † 1  46/662 (6.95%)  81 34/659 (5.16%)  59
Aspartate aminotransferase increased † 1  47/662 (7.10%)  58 19/659 (2.88%)  21
Gamma-glutamyltransferase increased † 1  34/662 (5.14%)  41 10/659 (1.52%)  13
Metabolism and nutrition disorders     
Decreased appetite † 1  118/662 (17.82%)  156 76/659 (11.53%)  106
Hypokalaemia † 1  45/662 (6.80%)  50 24/659 (3.64%)  35
Hyperglycaemia † 1  34/662 (5.14%)  44 14/659 (2.12%)  18
Musculoskeletal and connective tissue disorders     
Bone pain † 1  125/662 (18.88%)  200 66/659 (10.02%)  87
Arthralgia † 1  89/662 (13.44%)  113 77/659 (11.68%)  98
Myalgia † 1  80/662 (12.08%)  127 70/659 (10.62%)  87
Pain in extremity † 1  79/662 (11.93%)  108 67/659 (10.17%)  93
Back pain † 1  82/662 (12.39%)  96 49/659 (7.44%)  59
Muscle spasms † 1  40/662 (6.04%)  48 29/659 (4.40%)  34
Muscular weakness † 1  36/662 (5.44%)  41 17/659 (2.58%)  18
Nervous system disorders     
Peripheral sensory neuropathy † 1  189/662 (28.55%)  298 111/659 (16.84%)  149
Neuropathy peripheral † 1  174/662 (26.28%)  261 85/659 (12.90%)  103
Headache † 1  93/662 (14.05%)  124 92/659 (13.96%)  117
Paraesthesia † 1  84/662 (12.69%)  120 73/659 (11.08%)  89
Dizziness † 1  64/662 (9.67%)  74 57/659 (8.65%)  65
Dysgeusia † 1  48/662 (7.25%)  52 48/659 (7.28%)  68
Peripheral motor neuropathy † 1  40/662 (6.04%)  50 8/659 (1.21%)  9
Psychiatric disorders     
Insomnia † 1  126/662 (19.03%)  134 82/659 (12.44%)  89
Anxiety † 1  50/662 (7.55%)  53 49/659 (7.44%)  52
Depression † 1  35/662 (5.29%)  36 25/659 (3.79%)  27
Respiratory, thoracic and mediastinal disorders     
Cough † 1  97/662 (14.65%)  108 122/659 (18.51%)  139
Dyspnoea † 1  79/662 (11.93%)  97 121/659 (18.36%)  136
Oropharyngeal pain † 1  72/662 (10.88%)  82 55/659 (8.35%)  65
Rhinorrhoea † 1  40/662 (6.04%)  41 28/659 (4.25%)  31
Skin and subcutaneous tissue disorders     
Alopecia † 1  173/662 (26.13%)  194 146/659 (22.15%)  165
Rash maculo-papular † 1  43/662 (6.50%)  60 28/659 (4.25%)  33
1
Term from vocabulary, MedDRA (19.0)
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
EMail: trialdisclosures@takeda.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT01712490    
Other Study ID Numbers: C25003
2011-005450-60 ( EudraCT Number )
U1111-1161-4937 ( Registry Identifier: WHO )
12/LO/1950 ( Registry Identifier: NRES )
JapicCTI-142491 ( Registry Identifier: JapicCTI )
REec-2013-0114 ( Registry Identifier: REec )
1025002760 ( Registry Identifier: TCTIN )
C25003CTID ( Other Identifier: Israel )
2023-506419-16 ( Other Identifier: EU CTIS )
First Submitted: October 19, 2012
First Posted: October 23, 2012
Results First Submitted: April 18, 2018
Results First Posted: November 27, 2018
Last Update Posted: February 20, 2024