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A Frontline Therapy Trial in Participants With Advanced Classical Hodgkin Lymphoma

Sponsor
Takeda (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT01712490
Collaborator
Seagen Inc. (Industry)
1,334
Enrollment
216
Locations
2
Arms
158.2
Anticipated Duration (Months)
6.2
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This open-label, randomized, 2-arm, multicenter, phase 3 study has the primary objective of comparing the modified progression-free survival (mPFS) obtained with brentuximab vedotin (ADCETRIS®) plus AVD (doxorubicin [Adriamycin], vinblastine, and dacarbazine; abbreviated A+AVD) versus that obtained with ABVD (doxorubicin [Adriamycin],bleomycin, vinblastine, and dacarbazine) for the frontline treatment of advanced classical Hodgkin lymphoma(HL)

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

Phase 3 Frontline Therapy Trial in Patients With Advanced Classical Hodgkin Lymphoma

Study Design

Study Type:
Interventional
Actual Enrollment :
1334 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized, Open-label, Phase 3 Trial of A+AVD Versus ABVD as Frontline Therapy in Patients With Advanced Classical Hodgkin Lymphoma
Actual Study Start Date :
Nov 9, 2012
Actual Primary Completion Date :
Apr 20, 2017
Anticipated Study Completion Date :
Jan 15, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: A + AVD

A+AVD consists of brentuximab vedotin (ADCETRIS®) 1.2 milligram per kilogram (mg/kg) plus doxorubicin 25 milligram per square meter (mg/m^2), vinblastine 6 mg/m^2, and dacarbazine (DTIC) 375 mg/m^2.

Drug: brentuximab vedotin
Brentuximab vedotin (ADCETRIS®)1.2 mg/kg by IV infusion on Days 1 and 15 of each 28-day cycle.
Other Names:
  • ADCETRIS®
  • SGN-35

    • Drug: doxorubicin
    Doxorubicin: 25 mg/m^2 by IV infusion on Days 1 and 15 of each 28-day cycle.
    Other Names:
  • Adriamycin

    • Drug: vinblastine
    Vinblastine: 6 mg/m2 will be administered by IV infusion on Days 1 and 15 of each 28-day cycle

    Drug: dacarbazine
    Dacarbazine (DTIC): 375 mg/m^2 by IV infusion on Days 1 and 15 of each 28-day cycle.
    Other Names:
  • DTIC

    		•
    Active Comparator: ABVD

    ABVD consists of doxorubicin 25 mg/m^2, bleomycin 10 units per square meter (units/m^2), vinblastine 6 mg/m^2, and dacarbazine (DTIC) 375 mg/m^2.

    Drug: doxorubicin
    Doxorubicin: 25 mg/m^2 by IV infusion on Days 1 and 15 of each 28-day cycle.
    Other Names:
  • Adriamycin

    • Drug: bleomycin
    Bleomycin: 10 units/m^2 by IV infusion on Days 1 and 15 of each 28-day cycle.

    Drug: vinblastine
    Vinblastine: 6 mg/m2 will be administered by IV infusion on Days 1 and 15 of each 28-day cycle

    Drug: dacarbazine
    Dacarbazine (DTIC): 375 mg/m^2 by IV infusion on Days 1 and 15 of each 28-day cycle.
    Other Names:
  • DTIC

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Modified Progression-free Survival (mPFS) Per Independent Review Facility (IRF) [Baseline until PD or death or receipt of any subsequent anticancer therapy for HL after completion of frontline therapy (approximately up to 4 years)]

      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.

    Secondary Outcome Measures

    1. Overall Survival (OS) [Baseline until death (approximately up to 4 years)]

      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.

    2. Complete Remission (CR) Rate at the End of Randomized Regimen Per IRF [Baseline up to end of randomized regimen (approximately 1 year)]

      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.

    3. Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) [Baseline up to 30 days after last dose of study drug (approximately 1 year)]

    4. Number of Participants With Abnormal Clinical Laboratory Values [Baseline up to 30 days after last dose of study drug (approximately 1 year)]

    5. Event-free Survival (EFS) Per IRF [Baseline until PD or discontinuation of treatment or death, whichever occurs first (approximately up to 4 years)]

      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.

    6. Disease-free Survival (DFS) Per IRF [From CR until PD or death (approximately up to 4 years)]

      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.

    7. Overall Response Rate (ORR) Per IRF [Baseline up to end of randomized regimen (approximately 1 year)]

      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.

    8. Duration of Response (DOR) Per IRF [From first documented response until PD (approximately 4 years)]

      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.

    9. Duration of Complete Remission (DOCR) Per IRF [From first documentation of CR until PD (approximately 4 years)]

      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.

    10. Percentage of Participants Not in CR Per IRF Who Received Subsequent Radiation After Completion of Frontline Therapy [Baseline up to end of frontline therapy (approximately 4 years)]

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

    11. Complete Remission (CR) Per IRF Rate at the End of Frontline Therapy [Baseline up to end of frontline therapy (approximately 4 years)]

      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.

    12. Positron Emission Tomography (PET) Negativity Rate Per IRF at Cycle 2 [Cycle 2 Day 25]

      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.

    13. A+AVD: Cmax: Maximum Observed Serum Concentration for Brentuximab Vedotin Antibody-drug Conjugate (ADC) and Total Antibody (TAb) [Cycle 1 Day 1 and Cycle 3 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose]

    14. A+AVD: Cmax: Maximum Observed Plasma Concentration for Brentuximab Vedotin Monomethyl Auristatin E (MMAE) [Cycle 1 Day 1 and Cycle 3 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose]

    15. 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: pre-dose and at multiple timepoints (up to 48 hours) post-dose]

    16. A+AVD: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin MMAE [Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose]

    17. A+AVD: Number of Participants With Antitherapeutic Antibody (ATA) and Neutralizing Antitherapeutic Antibody (nATA) Positive for Brentuximab Vedotin [Baseline up to end of treatment (approximately 1 year)]

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

    18. 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 up to end of treatment (approximately 1 year)]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Treatment-naïve participants with Ann Arbor Stage III or IV HL.

    2. Histologically confirmed classical Hodgkin Lymphoma (HL) according to the current World Health Organization (WHO) classification.

    3. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (<=) 2.

    4. Bidimensional measurable disease as documented by radiographic technique per the International Working Group Revised Criteria for Response Assessment for Malignant Lymphoma.

    Exclusion Criteria:

    1. Nodular lymphocyte predominant Hodgkin lymphoma.

    2. Cerebral/meningeal disease, including signs and symptoms of progressive multifocalleukoencephalopathy (PML).

    3. Sensory or motor peripheral neuropathy.

    4. Prior immunosuppressive chemotherapy, therapeutic radiation, or any immunotherapy within 12 weeks of first study drug dose.

    5. Known human immunodeficiency virus (HIV) positive.

    6. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection.

    Please note that there are additional exclusion criteria. The study center will determine if you meet all of the criteria.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Birmingham Alabama United States
    2 Gilbert Arizona United States
    3 Tucson Arizona United States
    4 Burbank California United States
    5 Duarte California United States
    6 Fresno California United States
    7 Fullerton California United States
    8 La Jolla California United States
    9 Long Beach California United States
    10 Los Angeles California United States
    11 Sacramento California United States
    12 San Luis Obispo California United States
    13 Santa Barbara California United States
    14 Santa Monica California United States
    15 Stanford California United States
    16 Colorado Springs Colorado United States
    17 Denver Colorado United States
    18 Lonetree Colorado United States
    19 Washington District of Columbia United States
    20 Fort Myers Florida United States
    21 Jacksonville Florida United States
    22 Miami Florida United States
    23 Orlando Florida United States
    24 Lawrenceville Georgia United States
    25 Chicago Illinois United States
    26 Maywood Illinois United States
    27 Niles Illinois United States
    28 Zion Illinois United States
    29 Fort Wayne Indiana United States
    30 Goshen Indiana United States
    31 Indianapolis Indiana United States
    32 Iowa City Iowa United States
    33 Fairway Kansas United States
    34 Baltimore Maryland United States
    35 Bethesda Maryland United States
    36 Boston Massachusetts United States
    37 Ann Arbor Michigan United States
    38 Detroit Michigan United States
    39 Minneapolis Minnesota United States
    40 Rochester Minnesota United States
    41 Saint Louis Missouri United States
    42 Springfield Missouri United States
    43 Lincoln Nebraska United States
    44 Omaha Nebraska United States
    45 Las Vegas Nevada United States
    46 Basking Ridge New Jersey United States
    47 Hackensack New Jersey United States
    48 Morristown New Jersey United States
    49 Albuquerque New Mexico United States
    50 Albany New York United States
    51 Bronx New York United States
    52 Commack New York United States
    53 New York New York United States
    54 Rochester New York United States
    55 Rockville Centre New York United States
    56 Charlotte North Carolina United States
    57 Raleigh North Carolina United States
    58 Bismarck North Dakota United States
    59 Cincinnati Ohio United States
    60 Columbus Ohio United States
    61 Oklahoma City Oklahoma United States
    62 Eugene Oregon United States
    63 Hershey Pennsylvania United States
    64 Philadelphia Pennsylvania United States
    65 Charleston South Carolina United States
    66 Greenville South Carolina United States
    67 Chattanooga Tennessee United States
    68 Knoxville Tennessee United States
    69 Nashville Tennessee United States
    70 Austin Texas United States
    71 Dallas Texas United States
    72 Houston Texas United States
    73 San Antonio Texas United States
    74 Tyler Texas United States
    75 Salt Lake City Utah United States
    76 Fairfax Virginia United States
    77 Richmond Virginia United States
    78 Kennewick Washington United States
    79 Seattle Washington United States
    80 Vancouver Washington United States
    81 Yakima Washington United States
    82 Morgantown West Virginia United States
    83 Milwaukee Wisconsin United States
    84 Kingswood New South Wales Australia
    85 St Leonards New South Wales Australia
    86 Westmead New South Wales Australia
    87 South Brisbane Queensland Australia
    88 Bedford Park South Australia Australia
    89 Hobart Tasmania Australia
    90 East Melbourne Victoria Australia
    91 Geelong Victoria Australia
    92 Heidelberg Victoria Australia
    93 Parkville Victoria Australia
    94 Perth Western Australia Australia
    95 Antwerpen Belgium
    96 Brugge Belgium
    97 Gent Belgium
    98 Salvador Bahia Brazil
    99 Curitiba Parana Brazil
    100 Porto Alegre Rio Grande Do Sul Brazil
    101 Santo Andre Sao Paulo Brazil
    102 Rio De Janeiro Brazil
    103 Sao paulo Brazil
    104 Edmonton Alberta Canada
    105 Vancouver British Columbia Canada
    106 Winnipeg Manitoba Canada
    107 Halifax Nova Scotia Canada
    108 Toronto Ontario Canada
    109 Montreal Quebec Canada
    110 Saskatoon Saskatchewan Canada
    111 Hradec Kralove Czechia
    112 Prague Czechia
    113 Praha 10 Czechia
    114 Aalborg Denmark
    115 Aarhus C Denmark
    116 Copenhagen Denmark
    117 Odense C Denmark
    118 Roskilde Denmark
    119 Argenteuil Cedex France
    120 La Tronche France
    121 Limoges France
    122 Paris France
    123 Lai Chi Kok Kowloon Hong Kong
    124 Hong Kong Hong Kong
    125 Tuen Mun Hong Kong
    126 Budapest Hungary
    127 Debrecen Hungary
    128 Gyor Hungary
    129 Pecs Hungary
    130 Szeged Hungary
    131 Modena Emilia-Romagna Italy
    132 Roma Lazio Italy
    133 Alessandria Italy
    134 Bologna Italy
    135 Cagliari Italy
    136 Cuneo Italy
    137 Genova Italy
    138 Milano Italy
    139 Napoli Italy
    140 Rionero In Volture Italy
    141 Rome Italy
    142 Rozzano Italy
    143 Torrette Di Ancona Italy
    144 Minami-ku Fukuoka-city Japan
    145 Higashi-ku Fukuoka Japan
    146 Minami-ku Hiroshima-city Japan
    147 Showamachi Maebashi-city Japan
    148 Chikusa-ku Nagoya Japan
    149 Suita Osaka Prefecture Japan
    150 Aoba-ku Sendai-city Japan
    151 Chuo-ku Japan
    152 Isehara-shi Japan
    153 Koto-ku Japan
    154 Goyang Gyeonggi Korea, Republic of
    155 Hwasun-gun Jeollanam-do Korea, Republic of
    156 Seocho-gu Seoul Korea, Republic of
    157 Busan Korea, Republic of
    158 Daegu Korea, Republic of
    159 Incheon Korea, Republic of
    160 Jeonju Korea, Republic of
    161 Seoul Korea, Republic of
    162 Bergen Norway
    163 Oslo Norway
    164 Gdansk Poland
    165 Katowice Poland
    166 Krakow Poland
    167 L0dz Poland
    168 Olsztyn Poland
    169 Warszawa Poland
    170 Wroclaw Poland
    171 Saint-Petersburg Poselok Pesochny Russian Federation
    172 Ufa Republic Of Bashkortostan Russian Federation
    173 Kazan Republic Tatrstan Russian Federation
    174 Moscow Russian Federation
    175 Moskva Russian Federation
    176 St.Petersburg Russian Federation
    177 Johannesburg Gauteng South Africa
    178 Pretoria Gauteng South Africa
    179 Amanzimtoti Kwa Zulu Natal South Africa
    180 Bloemfontein South Africa
    181 Cape Town South Africa
    182 Badalona Spain
    183 Barcelona Spain
    184 Marbella Spain
    185 Pamplona Spain
    186 Salamanca Spain
    187 Santiago de Compostela Spain
    188 Valencia Spain
    189 Changhua City Taiwan
    190 Chiayi County 613 Taiwan
    191 Tainan Taiwan
    192 Taipei Taiwan
    193 Taoyuan County Taiwan
    194 Ankara Turkey
    195 Istanbul Turkey
    196 Samsun Turkey
    197 Truro Cornwall United Kingdom
    198 Aberdeen Scotland United Kingdom
    199 Glasgow Scotland United Kingdom
    200 Sutton Surrey United Kingdom
    201 Cardiff Wales United Kingdom
    202 Birmingham United Kingdom
    203 Canterbury United Kingdom
    204 Exeter United Kingdom
    205 Inverness United Kingdom
    206 Leicester United Kingdom
    207 Lincoln United Kingdom
    208 Liverpool United Kingdom
    209 London United Kingdom
    210 Manchester United Kingdom
    211 Norfolk United Kingdom
    212 Northwood United Kingdom
    213 Nottingham United Kingdom
    214 Oxford United Kingdom
    215 Romford United Kingdom
    216 Southampton United Kingdom

    Sponsors and Collaborators

    • Takeda
    • Seagen Inc.

    Investigators

    • Study Director: Study Director, Takeda

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Takeda
    ClinicalTrials.gov Identifier:
    NCT01712490
    Other Study ID Numbers:
    • C25003
    • 2011-005450-60
    • U1111-1161-4937
    • 12/LO/1950
    • JapicCTI-142491
    • REec-2013-0114
    • 1025002760
    • C25003CTID
    First Posted:
    Oct 23, 2012
    Last Update Posted:
    Feb 11, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Takeda
    Hodgkin Lymphoma
    Hodgkins Lymphoma
    Antibody, Monoclonal
    Antibody-Drug Conjugate
    Antigens, CD-30
    Immunotherapy
    Lymphoma
    Lymphoma, Classical
    ECHELON-1
    Additional relevant MeSH terms:
    Lymphoma
    Hodgkin Disease
    Doxorubicin
    Bleomycin
    Dacarbazine
    Brentuximab Vedotin
    Vinblastine

    Study Results

    Participant Flow

    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 Detail 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
    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

    Baseline Characteristics

    Arm/Group Title A+AVD ABVD Total
    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 Participants 664 670 1334
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    38.8
    (15.83)
    40.2
    (16.05)
    39.5
    (15.95)
    Sex: Female, Male (Count of Participants)
    Female
    286
    43.1%
    272
    40.6%
    558
    41.8%
    Male
    378
    56.9%
    398
    59.4%
    776
    58.2%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    51
    7.7%
    55
    8.2%
    106
    7.9%
    Not Hispanic or Latino
    571
    86%
    577
    86.1%
    1148
    86.1%
    Unknown or Not Reported
    42
    6.3%
    38
    5.7%
    80
    6%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    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%
    Black or African American
    20
    3%
    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%

    Outcome Measures

    1. Primary Outcome
    Title Modified Progression-free Survival (mPFS) Per Independent Review Facility (IRF)
    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)

    Outcome Measure Data

    Analysis Population Description
    The ITT population included all participants randomized to treatment.
    Arm/Group Title A+AVD ABVD
    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.
    Measure Participants 664 670
    Median (95% Confidence Interval) [months]
    NA
    NA
    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
    Statistical Test of Hypothesis p-Value 0.035
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.770
    Confidence Interval (2-Sided) 95%
    0.603 to 0.983
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Overall Survival (OS)
    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)

    Outcome Measure Data

    Analysis Population Description
    The ITT population included all participants randomized to treatment.
    Arm/Group Title A+AVD ABVD
    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.
    Measure Participants 664 670
    Median (95% Confidence Interval) [months]
    NA
    NA
    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
    Statistical Test of Hypothesis p-Value 0.199
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.728
    Confidence Interval (2-Sided) 95%
    0.448 to 1.184
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Complete Remission (CR) Rate at the End of Randomized Regimen Per IRF
    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)

    Outcome Measure Data

    Analysis Population Description
    The ITT population included all participants randomized to treatment.
    Arm/Group Title A+AVD ABVD
    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.
    Measure Participants 664 670
    Number [percentage of participants]
    73
    11%
    70
    10.4%
    4. Secondary Outcome
    Title Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
    Description
    Time Frame Baseline up to 30 days after last dose of study drug (approximately 1 year)

    Outcome Measure Data

    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
    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.
    Measure Participants 662 659
    TEAE
    653
    98.3%
    646
    96.4%
    SAE
    284
    42.8%
    178
    26.6%
    5. Secondary Outcome
    Title Number of Participants With Abnormal Clinical Laboratory Values
    Description
    Time Frame Baseline up to 30 days after last dose of study drug (approximately 1 year)

    Outcome Measure Data

    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
    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.
    Measure Participants 662 659
    Number [participants]
    662
    99.7%
    658
    98.2%
    6. Secondary Outcome
    Title Event-free Survival (EFS) Per IRF
    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)

    Outcome Measure Data

    Analysis Population Description
    The ITT population included all participants randomized to treatment.
    Arm/Group Title A+AVD ABVD
    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.
    Measure Participants 664 670
    Median (95% Confidence Interval) [months]
    NA
    NA
    7. Secondary Outcome
    Title Disease-free Survival (DFS) Per IRF
    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)

    Outcome Measure Data

    Analysis Population Description
    The ITT included all participants randomized to treatment. The ITT population where participants achieved CR.
    Arm/Group Title A+AVD ABVD
    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.
    Measure Participants 543 528
    Median (95% Confidence Interval) [months]
    NA
    NA
    8. Secondary Outcome
    Title Overall Response Rate (ORR) Per IRF
    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)

    Outcome Measure Data

    Analysis Population Description
    The ITT population included all participants randomized to treatment.
    Arm/Group Title A+AVD ABVD
    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.
    Measure Participants 664 670
    Number [percentage of participants]
    86
    13%
    83
    12.4%
    9. Secondary Outcome
    Title Duration of Response (DOR) Per IRF
    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)

    Outcome Measure Data

    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
    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.
    Measure Participants 628 623
    Median (95% Confidence Interval) [months]
    NA
    NA
    10. Secondary Outcome
    Title Duration of Complete Remission (DOCR) Per IRF
    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)

    Outcome Measure Data

    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
    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.
    Measure Participants 543 528
    Median (95% Confidence Interval) [months]
    NA
    NA
    11. Secondary Outcome
    Title Percentage of Participants Not in CR Per IRF Who Received Subsequent Radiation After Completion of Frontline Therapy
    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)

    Outcome Measure Data

    Analysis Population Description
    The ITT population included all participants randomized to treatment.
    Arm/Group Title A+AVD ABVD
    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.
    Measure Participants 664 670
    Number [percentage of participants]
    8
    1.2%
    13
    1.9%
    12. Secondary Outcome
    Title Complete Remission (CR) Per IRF Rate at the End of Frontline Therapy
    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)

    Outcome Measure Data

    Analysis Population Description
    The ITT population included all participants randomized to treatment.
    Arm/Group Title A+AVD ABVD
    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.
    Measure Participants 664 670
    Number [percentage of participants]
    73
    11%
    71
    10.6%
    13. Secondary Outcome
    Title Positron Emission Tomography (PET) Negativity Rate Per IRF at Cycle 2
    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

    Outcome Measure Data

    Analysis Population Description
    The ITT population included all participants randomized to treatment.
    Arm/Group Title A+AVD ABVD
    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.
    Measure Participants 664 670
    Number [percentage of participants]
    89
    13.4%
    86
    12.8%
    14. Secondary Outcome
    Title A+AVD: Cmax: Maximum Observed Serum Concentration for Brentuximab Vedotin Antibody-drug Conjugate (ADC) and Total Antibody (TAb)
    Description
    Time Frame Cycle 1 Day 1 and Cycle 3 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose

    Outcome Measure Data

    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
    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.
    Measure Participants 59
    Cycle 1 Day 1: ADC
    22.9
    (6.72)
    Cycle 3 Day 1: ADC
    23.6
    (6.81)
    Cycle 1 Day 1: TAb
    22.6
    (5.48)
    Cycle 3 Day 1: TAb
    26.4
    (6.11)
    15. Secondary Outcome
    Title A+AVD: Cmax: Maximum Observed Plasma Concentration for Brentuximab Vedotin Monomethyl Auristatin E (MMAE)
    Description
    Time Frame Cycle 1 Day 1 and Cycle 3 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose

    Outcome Measure Data

    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
    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.
    Measure Participants 59
    Cycle 1 Day 1
    3.20
    (2.99)
    Cycle 3 Day 1
    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
    Description
    Time Frame Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose

    Outcome Measure Data

    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
    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.
    Measure Participants 59
    Cycle 1 Day 1: ADC
    47.4
    (12.0)
    Cycle 1 Day 1: TAb
    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
    Description
    Time Frame Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose

    Outcome Measure Data

    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
    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.
    Measure Participants 59
    Mean (Standard Deviation) [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
    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)

    Outcome Measure Data

    Analysis Population Description
    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
    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.
    Measure Participants 632
    ATA positive
    109
    16.4%
    nATA positive
    12
    1.8%
    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
    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)

    Outcome Measure Data

    Analysis Population Description
    The ITT population included all participants randomized to treatment.
    Arm/Group Title A+AVD ABVD
    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.
    Measure Participants 664 670
    Baseline: With mPFS event
    78.15
    (16.527)
    76.68
    (18.661)
    Without mPFS event
    79.85
    (16.648)
    79.91
    (16.218)
    Change at end of treatment: with mPFS event
    2.68
    (15.434)
    8.58
    (17.848)
    Change at end of treatment: without mPFS event
    3.35
    (17.417)
    6.08
    (16.141)

    Adverse Events

    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
    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 (%) # Events Affected / at Risk (%) # Events
    Total 9/662 (1.4%) 13/659 (2%)
    Serious Adverse Events
    A+AVD ABVD
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 284/662 (42.9%) 178/659 (27%)
    Blood and lymphatic system disorders
    Febrile neutropenia 114/662 (17.2%) 151 43/659 (6.5%) 52
    Neutropenia 19/662 (2.9%) 30 4/659 (0.6%) 5
    Anaemia 7/662 (1.1%) 10 3/659 (0.5%) 3
    Lymphadenitis 0/662 (0%) 0 1/659 (0.2%) 1
    Lymphadenopathy mediastinal 1/662 (0.2%) 1 0/659 (0%) 0
    Pancytopenia 2/662 (0.3%) 2 0/659 (0%) 0
    Thrombocytopenia 1/662 (0.2%) 1 1/659 (0.2%) 1
    Histiocytosis haematophagic 1/662 (0.2%) 2 0/659 (0%) 0
    Cardiac disorders
    Myocardial infarction 3/662 (0.5%) 3 1/659 (0.2%) 1
    Acute myocardial infarction 0/662 (0%) 0 1/659 (0.2%) 1
    Angina pectoris 1/662 (0.2%) 1 0/659 (0%) 0
    Microvascular coronary artery disease 0/662 (0%) 0 1/659 (0.2%) 1
    Supraventricular tachycardia 2/662 (0.3%) 2 1/659 (0.2%) 1
    Atrial fibrillation 2/662 (0.3%) 2 0/659 (0%) 0
    Sinus tachycardia 1/662 (0.2%) 1 1/659 (0.2%) 1
    Tachycardia 2/662 (0.3%) 3 1/659 (0.2%) 1
    Cardiac arrest 0/662 (0%) 0 2/659 (0.3%) 2
    Cardio-respiratory arrest 1/662 (0.2%) 1 0/659 (0%) 0
    Cardiac failure 1/662 (0.2%) 1 0/659 (0%) 0
    Cardiopulmonary failure 0/662 (0%) 0 1/659 (0.2%) 1
    Pericarditis 1/662 (0.2%) 1 1/659 (0.2%) 1
    Atrial thrombosis 1/662 (0.2%) 1 0/659 (0%) 0
    Congenital, familial and genetic disorders
    Branchial cyst 1/662 (0.2%) 1 0/659 (0%) 0
    Endocrine disorders
    Cushing's syndrome 0/662 (0%) 0 1/659 (0.2%) 1
    Eye disorders
    Vision blurred 0/662 (0%) 0 1/659 (0.2%) 1
    Gastrointestinal disorders
    Abdominal pain 14/662 (2.1%) 15 4/659 (0.6%) 4
    Abdominal pain lower 1/662 (0.2%) 1 0/659 (0%) 0
    Vomiting 11/662 (1.7%) 11 3/659 (0.5%) 3
    Nausea 7/662 (1.1%) 7 3/659 (0.5%) 3
    Constipation 11/662 (1.7%) 12 6/659 (0.9%) 7
    Diarrhoea 11/662 (1.7%) 13 1/659 (0.2%) 1
    Colitis 4/662 (0.6%) 4 0/659 (0%) 0
    Neutropenic colitis 1/662 (0.2%) 1 0/659 (0%) 0
    Gastritis 2/662 (0.3%) 2 3/659 (0.5%) 4
    Ileus 3/662 (0.5%) 3 1/659 (0.2%) 1
    Ileus paralytic 4/662 (0.6%) 5 0/659 (0%) 0
    Pancreatitis 1/662 (0.2%) 1 0/659 (0%) 0
    Pancreatitis acute 1/662 (0.2%) 1 0/659 (0%) 0
    Enterocolitis 1/662 (0.2%) 1 1/659 (0.2%) 1
    Mouth ulceration 0/662 (0%) 0 1/659 (0.2%) 1
    Stomatitis 0/662 (0%) 0 1/659 (0.2%) 1
    Anal ulcer 0/662 (0%) 0 1/659 (0.2%) 1
    Gastrointestinal disorder 1/662 (0.2%) 1 0/659 (0%) 0
    Haemorrhoids 1/662 (0.2%) 1 0/659 (0%) 0
    General disorders
    Pyrexia 44/662 (6.6%) 55 28/659 (4.2%) 32
    Non-cardiac chest pain 1/662 (0.2%) 1 2/659 (0.3%) 3
    Pain 1/662 (0.2%) 2 1/659 (0.2%) 2
    Chest pain 0/662 (0%) 0 1/659 (0.2%) 1
    Fatigue 2/662 (0.3%) 2 0/659 (0%) 0
    Asthenia 1/662 (0.2%) 1 0/659 (0%) 0
    Malaise 1/662 (0.2%) 1 0/659 (0%) 0
    Multiple organ dysfunction syndrome 1/662 (0.2%) 1 1/659 (0.2%) 1
    Influenza like illness 1/662 (0.2%) 1 0/659 (0%) 0
    Peripheral swelling 0/662 (0%) 0 1/659 (0.2%) 1
    Chills 1/662 (0.2%) 1 2/659 (0.3%) 2
    Death 1/662 (0.2%) 1 1/659 (0.2%) 1
    Catheter site haemorrhage 0/662 (0%) 0 1/659 (0.2%) 1
    Catheter site pain 0/662 (0%) 0 1/659 (0.2%) 1
    Infusion site extravasation 1/662 (0.2%) 1 1/659 (0.2%) 1
    Complication associated with device 0/662 (0%) 0 1/659 (0.2%) 1
    Oedema peripheral 1/662 (0.2%) 1 0/659 (0%) 0
    Adverse drug reaction 0/662 (0%) 0 1/659 (0.2%) 1
    Device related thrombosis 0/662 (0%) 0 1/659 (0.2%) 1
    Hepatobiliary disorders
    Cholecystitis acute 1/662 (0.2%) 1 1/659 (0.2%) 1
    Cholelithiasis 1/662 (0.2%) 1 0/659 (0%) 0
    Hepatotoxicity 2/662 (0.3%) 2 0/659 (0%) 0
    Gallbladder obstruction 1/662 (0.2%) 1 0/659 (0%) 0
    Liver disorder 0/662 (0%) 0 1/659 (0.2%) 1
    Hepatic function abnormal 1/662 (0.2%) 1 0/659 (0%) 0
    Hepatic failure 1/662 (0.2%) 1 0/659 (0%) 0
    Immune system disorders
    Drug hypersensitivity 1/662 (0.2%) 1 1/659 (0.2%) 1
    Infections and infestations
    Pneumonia 18/662 (2.7%) 19 15/659 (2.3%) 18
    Lung infection 4/662 (0.6%) 4 2/659 (0.3%) 2
    Lower respiratory tract infection 2/662 (0.3%) 2 3/659 (0.5%) 3
    Bronchitis 1/662 (0.2%) 1 2/659 (0.3%) 2
    Atypical pneumonia 0/662 (0%) 0 1/659 (0.2%) 1
    Sepsis 14/662 (2.1%) 15 4/659 (0.6%) 4
    Neutropenic sepsis 8/662 (1.2%) 10 2/659 (0.3%) 2
    Bacteraemia 1/662 (0.2%) 1 4/659 (0.6%) 4
    Septic shock 4/662 (0.6%) 6 0/659 (0%) 0
    Septic embolus 0/662 (0%) 0 1/659 (0.2%) 1
    Device related infection 7/662 (1.1%) 8 2/659 (0.3%) 2
    Respiratory tract infection 1/662 (0.2%) 1 2/659 (0.3%) 2
    Infection 1/662 (0.2%) 1 1/659 (0.2%) 1
    Catheter site infection 1/662 (0.2%) 1 0/659 (0%) 0
    Lymph gland infection 0/662 (0%) 0 1/659 (0.2%) 1
    Pelvic infection 0/662 (0%) 0 1/659 (0.2%) 1
    Wound infection 0/662 (0%) 0 1/659 (0.2%) 1
    Upper respiratory tract infection 3/662 (0.5%) 3 2/659 (0.3%) 2
    Tonsillitis 1/662 (0.2%) 1 1/659 (0.2%) 1
    Laryngitis 0/662 (0%) 0 1/659 (0.2%) 1
    Pharyngeal abscess 1/662 (0.2%) 1 0/659 (0%) 0
    Pharyngitis 1/662 (0.2%) 1 0/659 (0%) 0
    Sinusitis 1/662 (0.2%) 1 0/659 (0%) 0
    Cellulitis 5/662 (0.8%) 5 2/659 (0.3%) 2
    Bacterial infection 0/662 (0%) 0 1/659 (0.2%) 1
    Cellulitis orbital 1/662 (0.2%) 1 0/659 (0%) 0
    Gangrene 0/662 (0%) 0 1/659 (0.2%) 1
    Pneumocystis jirovecii pneumonia 5/662 (0.8%) 5 2/659 (0.3%) 3
    Pneumocystis jirovecii infection 1/662 (0.2%) 1 0/659 (0%) 0
    Anal abscess 2/662 (0.3%) 2 0/659 (0%) 0
    Abdominal abscess 0/662 (0%) 0 1/659 (0.2%) 1
    Appendicitis 1/662 (0.2%) 1 0/659 (0%) 0
    Diverticulitis 1/662 (0.2%) 1 0/659 (0%) 0
    Enteritis infectious 0/662 (0%) 0 1/659 (0.2%) 1
    Skin infection 2/662 (0.3%) 3 1/659 (0.2%) 1
    Subcutaneous abscess 1/662 (0.2%) 1 1/659 (0.2%) 1
    Folliculitis 1/662 (0.2%) 1 0/659 (0%) 0
    Gastroenteritis viral 1/662 (0.2%) 1 2/659 (0.3%) 2
    Pneumonia viral 2/662 (0.3%) 2 0/659 (0%) 0
    Viral infection 1/662 (0.2%) 1 0/659 (0%) 0
    Clostridium difficile colitis 2/662 (0.3%) 2 1/659 (0.2%) 1
    Clostridium difficile infection 1/662 (0.2%) 1 0/659 (0%) 0
    Tooth abscess 2/662 (0.3%) 2 0/659 (0%) 0
    Pericoronitis 1/662 (0.2%) 1 0/659 (0%) 0
    Periodontitis 0/662 (0%) 0 1/659 (0.2%) 1
    Staphylococcal infection 1/662 (0.2%) 1 1/659 (0.2%) 1
    Staphylococcal bacteraemia 0/662 (0%) 0 1/659 (0.2%) 1
    Staphylococcal sepsis 1/662 (0.2%) 1 0/659 (0%) 0
    Urinary tract infection 2/662 (0.3%) 2 1/659 (0.2%) 1
    Pyelonephritis 0/662 (0%) 0 1/659 (0.2%) 1
    Soft tissue infection 1/662 (0.2%) 1 2/659 (0.3%) 2
    Aspergillus infection 0/662 (0%) 0 1/659 (0.2%) 1
    Bronchopulmonary aspergillosis 1/662 (0.2%) 1 0/659 (0%) 0
    Genital infection female 0/662 (0%) 0 1/659 (0.2%) 1
    Vulvitis 1/662 (0.2%) 1 0/659 (0%) 0
    Fungal sepsis 0/662 (0%) 0 1/659 (0.2%) 1
    Pneumonia fungal 0/662 (0%) 0 1/659 (0.2%) 1
    Herpes virus infection 1/662 (0.2%) 1 0/659 (0%) 0
    Herpes zoster 0/662 (0%) 0 1/659 (0.2%) 1
    Ophthalmic herpes zoster 0/662 (0%) 0 1/659 (0.2%) 1
    Infected lymphocele 1/662 (0.2%) 1 0/659 (0%) 0
    Phlebitis infective 0/662 (0%) 0 1/659 (0.2%) 1
    Endocarditis 0/662 (0%) 0 1/659 (0.2%) 1
    Encephalitis 1/662 (0.2%) 1 0/659 (0%) 0
    Flavivirus infection 1/662 (0.2%) 1 0/659 (0%) 0
    Hepatitis B 0/662 (0%) 0 1/659 (0.2%) 2
    Influenza 1/662 (0.2%) 1 0/659 (0%) 0
    Moraxella infection 0/662 (0%) 0 1/659 (0.2%) 1
    Parainfluenzae virus infection 0/662 (0%) 0 1/659 (0.2%) 1
    Pneumonia streptococcal 1/662 (0.2%) 1 0/659 (0%) 0
    Injury, poisoning and procedural complications
    Hip fracture 2/662 (0.3%) 2 0/659 (0%) 0
    Ankle fracture 1/662 (0.2%) 1 0/659 (0%) 0
    Femur fracture 1/662 (0.2%) 1 0/659 (0%) 0
    Infusion related reaction 1/662 (0.2%) 1 1/659 (0.2%) 1
    Fall 0/662 (0%) 0 1/659 (0.2%) 1
    Investigations
    Neutrophil count decreased 3/662 (0.5%) 3 1/659 (0.2%) 1
    Pseudomonas test positive 0/662 (0%) 0 1/659 (0.2%) 1
    Staphylococcus test positive 0/662 (0%) 0 1/659 (0.2%) 1
    Blood glucose increased 1/662 (0.2%) 1 0/659 (0%) 0
    Amylase increased 1/662 (0.2%) 1 0/659 (0%) 0
    Lipase increased 1/662 (0.2%) 1 0/659 (0%) 0
    Electrocardiogram QT prolonged 1/662 (0.2%) 2 0/659 (0%) 0
    Blood bilirubin increased 1/662 (0.2%) 1 0/659 (0%) 0
    Body temperature increased 0/662 (0%) 0 1/659 (0.2%) 1
    Metabolism and nutrition disorders
    Dehydration 10/662 (1.5%) 10 3/659 (0.5%) 3
    Hyponatraemia 4/662 (0.6%) 4 3/659 (0.5%) 3
    Hyperglycaemia 3/662 (0.5%) 4 1/659 (0.2%) 1
    Hypokalaemia 2/662 (0.3%) 2 1/659 (0.2%) 1
    Hyperkalaemia 0/662 (0%) 0 1/659 (0.2%) 1
    Failure to thrive 1/662 (0.2%) 1 0/659 (0%) 0
    Malnutrition 1/662 (0.2%) 1 0/659 (0%) 0
    Hypomagnesaemia 2/662 (0.3%) 2 0/659 (0%) 0
    Type 2 diabetes mellitus 1/662 (0.2%) 1 0/659 (0%) 0
    Hypophosphataemia 1/662 (0.2%) 1 0/659 (0%) 0
    Musculoskeletal and connective tissue disorders
    Pain in extremity 2/662 (0.3%) 2 1/659 (0.2%) 1
    Back pain 2/662 (0.3%) 2 0/659 (0%) 0
    Flank pain 2/662 (0.3%) 2 0/659 (0%) 0
    Musculoskeletal pain 1/662 (0.2%) 2 0/659 (0%) 0
    Myalgia 1/662 (0.2%) 1 1/659 (0.2%) 1
    Bone pain 1/662 (0.2%) 1 0/659 (0%) 0
    Arthralgia 0/662 (0%) 0 1/659 (0.2%) 1
    Muscular weakness 0/662 (0%) 0 1/659 (0.2%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neuroendocrine tumour 0/662 (0%) 0 1/659 (0.2%) 1
    Pituitary tumour 1/662 (0.2%) 1 0/659 (0%) 0
    T-cell lymphoma 0/662 (0%) 0 1/659 (0.2%) 1
    Bile duct cancer 0/662 (0%) 0 1/659 (0.2%) 1
    Gastrointestinal stromal tumour 1/662 (0.2%) 1 0/659 (0%) 0
    Benign ovarian tumour 0/662 (0%) 0 1/659 (0.2%) 1
    Plasma cell myeloma 1/662 (0.2%) 1 0/659 (0%) 0
    Nervous system disorders
    Syncope 2/662 (0.3%) 3 2/659 (0.3%) 2
    Lethargy 2/662 (0.3%) 2 1/659 (0.2%) 1
    Somnolence 0/662 (0%) 0 1/659 (0.2%) 1
    Headache 3/662 (0.5%) 3 3/659 (0.5%) 3
    Peripheral motor neuropathy 3/662 (0.5%) 3 0/659 (0%) 0
    Peripheral sensory neuropathy 2/662 (0.3%) 2 0/659 (0%) 0
    Polyneuropathy 1/662 (0.2%) 1 1/659 (0.2%) 1
    Cerebrovascular accident 1/662 (0.2%) 1 1/659 (0.2%) 1
    Lacunar infarction 0/662 (0%) 0 1/659 (0.2%) 1
    Autonomic neuropathy 0/662 (0%) 0 1/659 (0.2%) 1
    Facial paralysis 1/662 (0.2%) 1 0/659 (0%) 0
    Hypoaesthesia 1/662 (0.2%) 3 0/659 (0%) 0
    Hemiparesis 1/662 (0.2%) 3 0/659 (0%) 0
    Neuralgia 1/662 (0.2%) 1 0/659 (0%) 0
    Spinal cord ischaemia 1/662 (0.2%) 1 0/659 (0%) 0
    Psychiatric disorders
    Anxiety 2/662 (0.3%) 2 1/659 (0.2%) 2
    Agitation 0/662 (0%) 0 1/659 (0.2%) 1
    Delirium 2/662 (0.3%) 2 0/659 (0%) 0
    Schizoaffective disorder bipolar type 0/662 (0%) 0 1/659 (0.2%) 1
    Suicidal ideation 1/662 (0.2%) 1 0/659 (0%) 0
    Renal and urinary disorders
    Acute kidney injury 3/662 (0.5%) 3 0/659 (0%) 0
    Anuria 1/662 (0.2%) 1 0/659 (0%) 0
    Ureteric obstruction 1/662 (0.2%) 1 1/659 (0.2%) 1
    Haematuria 0/662 (0%) 0 1/659 (0.2%) 1
    Reproductive system and breast disorders
    Metrorrhagia 0/662 (0%) 0 1/659 (0.2%) 1
    Vaginal haemorrhage 0/662 (0%) 0 1/659 (0.2%) 1
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism 11/662 (1.7%) 11 9/659 (1.4%) 9
    Pulmonary thrombosis 1/662 (0.2%) 1 0/659 (0%) 0
    Pneumonitis 2/662 (0.3%) 2 12/659 (1.8%) 13
    Pulmonary toxicity 0/662 (0%) 0 5/659 (0.8%) 6
    Interstitial lung disease 1/662 (0.2%) 1 2/659 (0.3%) 2
    Lung infiltration 2/662 (0.3%) 2 0/659 (0%) 0
    Organising pneumonia 0/662 (0%) 0 1/659 (0.2%) 1
    Dyspnoea 3/662 (0.5%) 3 5/659 (0.8%) 5
    Respiratory failure 2/662 (0.3%) 3 4/659 (0.6%) 4
    Hypoxia 1/662 (0.2%) 1 2/659 (0.3%) 2
    Cough 1/662 (0.2%) 1 1/659 (0.2%) 1
    Acute pulmonary oedema 1/662 (0.2%) 1 0/659 (0%) 0
    Acute respiratory distress syndrome 0/662 (0%) 0 1/659 (0.2%) 1
    Lung disorder 1/662 (0.2%) 1 0/659 (0%) 0
    Respiratory disorder 0/662 (0%) 0 1/659 (0.2%) 1
    Chronic obstructive pulmonary disease 1/662 (0.2%) 2 0/659 (0%) 0
    Stridor 1/662 (0.2%) 1 0/659 (0%) 0
    Pleuritic pain 0/662 (0%) 0 1/659 (0.2%) 1
    Pleurisy 1/662 (0.2%) 1 0/659 (0%) 0
    Pneumothorax 1/662 (0.2%) 1 0/659 (0%) 0
    Skin and subcutaneous tissue disorders
    Rash macular 1/662 (0.2%) 4 0/659 (0%) 0
    Rash maculo-papular 1/662 (0.2%) 1 0/659 (0%) 0
    Hidradenitis 0/662 (0%) 0 1/659 (0.2%) 1
    Drug eruption 0/662 (0%) 0 1/659 (0.2%) 1
    Skin ulcer 0/662 (0%) 0 1/659 (0.2%) 1
    Vascular disorders
    Deep vein thrombosis 5/662 (0.8%) 5 2/659 (0.3%) 3
    Thrombophlebitis superficial 1/662 (0.2%) 1 1/659 (0.2%) 1
    Jugular vein thrombosis 0/662 (0%) 0 1/659 (0.2%) 1
    Pelvic venous thrombosis 1/662 (0.2%) 1 0/659 (0%) 0
    Peripheral artery thrombosis 1/662 (0.2%) 1 0/659 (0%) 0
    Venous thrombosis limb 0/662 (0%) 0 1/659 (0.2%) 1
    Hypotension 4/662 (0.6%) 4 1/659 (0.2%) 1
    Orthostatic hypotension 0/662 (0%) 0 1/659 (0.2%) 1
    Embolism 0/662 (0%) 0 4/659 (0.6%) 4
    Venous thrombosis 1/662 (0.2%) 1 0/659 (0%) 0
    Brachiocephalic vein occlusion 0/662 (0%) 0 1/659 (0.2%) 1
    Superior vena cava syndrome 1/662 (0.2%) 1 0/659 (0%) 0
    Phlebitis 1/662 (0.2%) 1 0/659 (0%) 0
    Vena cava thrombosis 0/662 (0%) 0 1/659 (0.2%) 1
    Other (Not Including Serious) Adverse Events
    A+AVD ABVD
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 644/662 (97.3%) 632/659 (95.9%)
    Blood and lymphatic system disorders
    Neutropenia 374/662 (56.5%) 1169 291/659 (44.2%) 813
    Anaemia 136/662 (20.5%) 237 65/659 (9.9%) 97
    Leukopenia 42/662 (6.3%) 124 37/659 (5.6%) 118
    Gastrointestinal disorders
    Nausea 346/662 (52.3%) 673 369/659 (56%) 735
    Constipation 273/662 (41.2%) 361 239/659 (36.3%) 336
    Vomiting 212/662 (32%) 342 183/659 (27.8%) 284
    Diarrhoea 176/662 (26.6%) 231 121/659 (18.4%) 155
    Stomatitis 138/662 (20.8%) 182 104/659 (15.8%) 135
    Abdominal pain 135/662 (20.4%) 185 65/659 (9.9%) 79
    Dyspepsia 84/662 (12.7%) 100 75/659 (11.4%) 93
    Abdominal pain upper 64/662 (9.7%) 74 34/659 (5.2%) 37
    Gastrooesophageal reflux disease 33/662 (5%) 36 47/659 (7.1%) 49
    General disorders
    Fatigue 209/662 (31.6%) 272 211/659 (32%) 293
    Pyrexia 149/662 (22.5%) 224 128/659 (19.4%) 191
    Asthenia 65/662 (9.8%) 97 42/659 (6.4%) 66
    Chills 37/662 (5.6%) 52 46/659 (7%) 51
    Non-cardiac chest pain 37/662 (5.6%) 40 45/659 (6.8%) 53
    Infections and infestations
    Upper respiratory tract infection 68/662 (10.3%) 76 69/659 (10.5%) 75
    Nasopharyngitis 28/662 (4.2%) 39 35/659 (5.3%) 40
    Investigations
    Weight decreased 148/662 (22.4%) 168 40/659 (6.1%) 46
    Neutrophil count decreased 86/662 (13%) 285 78/659 (11.8%) 191
    Alanine aminotransferase increased 68/662 (10.3%) 92 26/659 (3.9%) 28
    White blood cell count decreased 46/662 (6.9%) 81 34/659 (5.2%) 59
    Aspartate aminotransferase increased 47/662 (7.1%) 58 19/659 (2.9%) 21
    Gamma-glutamyltransferase increased 34/662 (5.1%) 41 10/659 (1.5%) 13
    Metabolism and nutrition disorders
    Decreased appetite 118/662 (17.8%) 156 76/659 (11.5%) 106
    Hypokalaemia 45/662 (6.8%) 50 24/659 (3.6%) 35
    Hyperglycaemia 34/662 (5.1%) 44 14/659 (2.1%) 18
    Musculoskeletal and connective tissue disorders
    Bone pain 125/662 (18.9%) 200 66/659 (10%) 87
    Arthralgia 89/662 (13.4%) 113 77/659 (11.7%) 98
    Myalgia 80/662 (12.1%) 127 70/659 (10.6%) 87
    Pain in extremity 79/662 (11.9%) 108 67/659 (10.2%) 93
    Back pain 82/662 (12.4%) 96 49/659 (7.4%) 59
    Muscle spasms 40/662 (6%) 48 29/659 (4.4%) 34
    Muscular weakness 36/662 (5.4%) 41 17/659 (2.6%) 18
    Nervous system disorders
    Peripheral sensory neuropathy 189/662 (28.5%) 298 111/659 (16.8%) 149
    Neuropathy peripheral 174/662 (26.3%) 261 85/659 (12.9%) 103
    Headache 93/662 (14%) 124 92/659 (14%) 117
    Paraesthesia 84/662 (12.7%) 120 73/659 (11.1%) 89
    Dizziness 64/662 (9.7%) 74 57/659 (8.6%) 65
    Dysgeusia 48/662 (7.3%) 52 48/659 (7.3%) 68
    Peripheral motor neuropathy 40/662 (6%) 50 8/659 (1.2%) 9
    Psychiatric disorders
    Insomnia 126/662 (19%) 134 82/659 (12.4%) 89
    Anxiety 50/662 (7.6%) 53 49/659 (7.4%) 52
    Depression 35/662 (5.3%) 36 25/659 (3.8%) 27
    Respiratory, thoracic and mediastinal disorders
    Cough 97/662 (14.7%) 108 122/659 (18.5%) 139
    Dyspnoea 79/662 (11.9%) 97 121/659 (18.4%) 136
    Oropharyngeal pain 72/662 (10.9%) 82 55/659 (8.3%) 65
    Rhinorrhoea 40/662 (6%) 41 28/659 (4.2%) 31
    Skin and subcutaneous tissue disorders
    Alopecia 173/662 (26.1%) 194 146/659 (22.2%) 165
    Rash maculo-papular 43/662 (6.5%) 60 28/659 (4.2%) 33

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    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

    Name/Title Medical Director
    Organization Takeda
    Phone +1-877-825-3327
    Email trialdisclosures@takeda.com
    Responsible Party:
    Takeda
    ClinicalTrials.gov Identifier:
    NCT01712490
    Other Study ID Numbers:
    • C25003
    • 2011-005450-60
    • U1111-1161-4937
    • 12/LO/1950
    • JapicCTI-142491
    • REec-2013-0114
    • 1025002760
    • C25003CTID
    First Posted:
    Oct 23, 2012
    Last Update Posted:
    Feb 11, 2022
    Last Verified:
    Feb 1, 2022