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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01712490




Registration number
NCT01712490
Ethics application status
Date submitted
19/10/2012
Date registered
23/10/2012

Titles & IDs
Public title
A Frontline Therapy Trial in Participants With Advanced Classical Hodgkin Lymphoma
Scientific title
A Randomized, Open-label, Phase 3 Trial of A+AVD Versus ABVD as Frontline Therapy in Patients With Advanced Classical Hodgkin Lymphoma
Secondary ID [1] 0 0
2011-005450-60
Secondary ID [2] 0 0
C25003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hodgkin Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Hodgkin's

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - brentuximab vedotin
Treatment: Drugs - doxorubicin
Treatment: Drugs - bleomycin
Treatment: Drugs - vinblastine
Treatment: Drugs - dacarbazine

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.

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.


Treatment: Drugs: brentuximab vedotin
Brentuximab vedotin (ADCETRIS®)1.2 mg/kg by IV infusion on Days 1 and 15 of each 28-day cycle.

Treatment: Drugs: doxorubicin
Doxorubicin: 25 mg/m\^2 by IV infusion on Days 1 and 15 of each 28-day cycle.

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

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

Treatment: Drugs: dacarbazine
Dacarbazine (DTIC): 375 mg/m\^2 by IV infusion on Days 1 and 15 of each 28-day cycle.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Modified Progression-free Survival (mPFS) Per Independent Review Facility (IRF)
Timepoint [1] 0 0
Baseline until PD or death or receipt of any subsequent anticancer therapy for HL after completion of frontline therapy (approximately up to 4 years)
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Baseline until death (approximately up to 4 years)
Secondary outcome [2] 0 0
Complete Remission (CR) Rate at the End of Randomized Regimen Per IRF
Timepoint [2] 0 0
Baseline up to end of randomized regimen (approximately 1 year)
Secondary outcome [3] 0 0
Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
Timepoint [3] 0 0
Baseline up to 30 days after last dose of study drug (approximately 1 year)
Secondary outcome [4] 0 0
Number of Participants With Abnormal Clinical Laboratory Values
Timepoint [4] 0 0
Baseline up to 30 days after last dose of study drug (approximately 1 year)
Secondary outcome [5] 0 0
Event-free Survival (EFS) Per IRF
Timepoint [5] 0 0
Baseline until PD or discontinuation of treatment or death, whichever occurs first (approximately up to 4 years)
Secondary outcome [6] 0 0
Disease-free Survival (DFS) Per IRF
Timepoint [6] 0 0
From CR until PD or death (approximately up to 4 years)
Secondary outcome [7] 0 0
Overall Response Rate (ORR) Per IRF
Timepoint [7] 0 0
Baseline up to end of randomized regimen (approximately 1 year)
Secondary outcome [8] 0 0
Duration of Response (DOR) Per IRF
Timepoint [8] 0 0
From first documented response until PD (approximately 4 years)
Secondary outcome [9] 0 0
Duration of Complete Remission (DOCR) Per IRF
Timepoint [9] 0 0
From first documentation of CR until PD (approximately 4 years)
Secondary outcome [10] 0 0
Percentage of Participants Not in CR Per IRF Who Received Subsequent Radiation After Completion of Frontline Therapy
Timepoint [10] 0 0
Baseline up to end of frontline therapy (approximately 4 years)
Secondary outcome [11] 0 0
Complete Remission (CR) Per IRF Rate at the End of Frontline Therapy
Timepoint [11] 0 0
Baseline up to end of frontline therapy (approximately 4 years)
Secondary outcome [12] 0 0
Positron Emission Tomography (PET) Negativity Rate Per IRF at Cycle 2
Timepoint [12] 0 0
Cycle 2 Day 25
Secondary outcome [13] 0 0
A+AVD: Cmax: Maximum Observed Serum Concentration for Brentuximab Vedotin Antibody-drug Conjugate (ADC) and Total Antibody (TAb)
Timepoint [13] 0 0
Cycle 1 Day 1 and Cycle 3 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose
Secondary outcome [14] 0 0
A+AVD: Cmax: Maximum Observed Plasma Concentration for Brentuximab Vedotin Monomethyl Auristatin E (MMAE)
Timepoint [14] 0 0
Cycle 1 Day 1 and Cycle 3 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose
Secondary outcome [15] 0 0
A+AVD: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin ADC and TAb
Timepoint [15] 0 0
Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose
Secondary outcome [16] 0 0
A+AVD: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin MMAE
Timepoint [16] 0 0
Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose
Secondary outcome [17] 0 0
A+AVD: Number of Participants With Antitherapeutic Antibody (ATA) and Neutralizing Antitherapeutic Antibody (nATA) Positive for Brentuximab Vedotin
Timepoint [17] 0 0
Baseline up to end of treatment (approximately 1 year)
Secondary outcome [18] 0 0
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
Timepoint [18] 0 0
Baseline up to end of treatment (approximately 1 year)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
- Kingswood
Recruitment hospital [2] 0 0
- St Leonards
Recruitment hospital [3] 0 0
- Westmead
Recruitment hospital [4] 0 0
- South Brisbane
Recruitment hospital [5] 0 0
- Bedford Park
Recruitment hospital [6] 0 0
- Hobart
Recruitment hospital [7] 0 0
- East Melbourne
Recruitment hospital [8] 0 0
- Geelong
Recruitment hospital [9] 0 0
- Heidelberg
Recruitment hospital [10] 0 0
- Parkville
Recruitment hospital [11] 0 0
- Perth
Recruitment postcode(s) [1] 0 0
- Kingswood
Recruitment postcode(s) [2] 0 0
- St Leonards
Recruitment postcode(s) [3] 0 0
- Westmead
Recruitment postcode(s) [4] 0 0
- South Brisbane
Recruitment postcode(s) [5] 0 0
- Bedford Park
Recruitment postcode(s) [6] 0 0
- Hobart
Recruitment postcode(s) [7] 0 0
- East Melbourne
Recruitment postcode(s) [8] 0 0
- Geelong
Recruitment postcode(s) [9] 0 0
- Heidelberg
Recruitment postcode(s) [10] 0 0
- Parkville
Recruitment postcode(s) [11] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
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Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
District of Columbia
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United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
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Georgia
Country [8] 0 0
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State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
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Indiana
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State/province [10] 0 0
Iowa
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Kansas
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Missouri
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Nebraska
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Nevada
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New Jersey
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New Mexico
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New York
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North Carolina
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North Dakota
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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South Carolina
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Tennessee
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Texas
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Utah
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Virginia
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Washington
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West Virginia
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United States of America
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Wisconsin
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Belgium
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Antwerpen
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Belgium
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Brugge
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Belgium
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Gent
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Brazil
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Bahia
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Brazil
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Parana
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Rio Grande Do Sul
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Sao Paulo
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Rio De Janeiro
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Sao paulo
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Alberta
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British Columbia
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Canada
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Manitoba
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Nova Scotia
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Ontario
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Quebec
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Saskatchewan
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Czechia
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Hradec Kralove
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Prague
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Czechia
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Praha 10
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Aalborg
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Aarhus C
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Copenhagen
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Odense C
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Roskilde
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France
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Cedex
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La Tronche
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Limoges
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Paris
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Kowloon
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Tuen Mun
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Hungary
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Budapest
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Hungary
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Debrecen
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Gyor
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Pecs
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Szeged
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Lazio
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Bologna
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Cuneo
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Genova
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Milano
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Italy
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Napoli
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Italy
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Rionero In Volture
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Italy
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Rome
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Italy
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Rozzano
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Italy
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Torrette Di Ancona
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Japan
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Fukuoka-city
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Japan
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Fukuoka
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Japan
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Hiroshima-city
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Japan
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Maebashi-city
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Japan
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Nagoya
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Japan
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Osaka Prefecture
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Japan
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Sendai-city
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Japan
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Chuo-ku
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Japan
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Isehara-shi
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Japan
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Koto-ku
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Korea, Republic of
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Gyeonggi
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Korea, Republic of
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Jeollanam-do
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Korea, Republic of
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Seoul
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Korea, Republic of
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Busan
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Korea, Republic of
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Daegu
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Incheon
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Jeonju
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Norway
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Bergen
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Norway
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Oslo
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Poland
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Gdansk
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Krakow
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L0dz
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Olsztyn
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Wroclaw
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Russian Federation
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Poselok Pesochny
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Russian Federation
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Republic Of Bashkortostan
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Russian Federation
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Republic Tatrstan
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Russian Federation
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Moscow
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Russian Federation
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Moskva
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Russian Federation
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St.Petersburg
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South Africa
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Gauteng
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South Africa
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Kwa Zulu Natal
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South Africa
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Bloemfontein
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South Africa
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Cape Town
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Spain
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Badalona
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Spain
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Barcelona
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Spain
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Marbella
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Spain
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Pamplona
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Spain
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Salamanca
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Spain
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Santiago de Compostela
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Spain
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Valencia
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Taiwan
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Changhua City
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Taiwan
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Chiayi County 613
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Taiwan
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Tainan
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Taiwan
State/province [131] 0 0
Taipei
Country [132] 0 0
Taiwan
State/province [132] 0 0
Taoyuan County
Country [133] 0 0
Turkey
State/province [133] 0 0
Ankara
Country [134] 0 0
Turkey
State/province [134] 0 0
Istanbul
Country [135] 0 0
Turkey
State/province [135] 0 0
Samsun
Country [136] 0 0
United Kingdom
State/province [136] 0 0
Cornwall
Country [137] 0 0
United Kingdom
State/province [137] 0 0
Scotland
Country [138] 0 0
United Kingdom
State/province [138] 0 0
Surrey
Country [139] 0 0
United Kingdom
State/province [139] 0 0
Wales
Country [140] 0 0
United Kingdom
State/province [140] 0 0
Birmingham
Country [141] 0 0
United Kingdom
State/province [141] 0 0
Canterbury
Country [142] 0 0
United Kingdom
State/province [142] 0 0
Exeter
Country [143] 0 0
United Kingdom
State/province [143] 0 0
Inverness
Country [144] 0 0
United Kingdom
State/province [144] 0 0
Leicester
Country [145] 0 0
United Kingdom
State/province [145] 0 0
Lincoln
Country [146] 0 0
United Kingdom
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Liverpool
Country [147] 0 0
United Kingdom
State/province [147] 0 0
London
Country [148] 0 0
United Kingdom
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Manchester
Country [149] 0 0
United Kingdom
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Norfolk
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United Kingdom
State/province [150] 0 0
Northwood
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United Kingdom
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Nottingham
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United Kingdom
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Oxford
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United Kingdom
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Romford
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United Kingdom
State/province [154] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Takeda
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Seagen Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
Takeda
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
Available to whom?
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/ourmember/takeda/


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.