A Frontline Therapy Trial in Participants With Advanced Classical Hodgkin Lymphoma

NCT ID: NCT01712490

Last Updated: 2025-11-10

Study Results

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

1334 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-11-09

Study Completion Date

2026-01-20

Brief Summary

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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)

Detailed Description

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Conditions

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Hodgkin Lymphoma

Keywords

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Hodgkin Lymphoma Hodgkins Lymphoma Antibody, Monoclonal Antibody-Drug Conjugate Antigens, CD-30 Immunotherapy Lymphoma Lymphoma, Classical ECHELON-1

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

brentuximab vedotin

Intervention Type DRUG

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

doxorubicin

Intervention Type DRUG

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

vinblastine

Intervention Type DRUG

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

dacarbazine

Intervention Type DRUG

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

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.

Group Type ACTIVE_COMPARATOR

doxorubicin

Intervention Type DRUG

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

bleomycin

Intervention Type DRUG

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

vinblastine

Intervention Type DRUG

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

dacarbazine

Intervention Type DRUG

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

Interventions

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brentuximab vedotin

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

Intervention Type DRUG

doxorubicin

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

Intervention Type DRUG

bleomycin

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

Intervention Type DRUG

vinblastine

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

Intervention Type DRUG

dacarbazine

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

Intervention Type DRUG

Other Intervention Names

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ADCETRIS® SGN-35 Adriamycin DTIC

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Seagen Inc.

INDUSTRY

Sponsor Role collaborator

Takeda

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

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Birmingham, Alabama, United States

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Gilbert, Arizona, United States

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Tucson, Arizona, United States

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Burbank, California, United States

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Duarte, California, United States

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Fresno, California, United States

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Fullerton, California, United States

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La Jolla, California, United States

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Long Beach, California, United States

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Los Angeles, California, United States

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Sacramento, California, United States

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San Luis Obispo, California, United States

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Santa Barbara, California, United States

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Santa Monica, California, United States

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Stanford, California, United States

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Colorado Springs, Colorado, United States

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Denver, Colorado, United States

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Lonetree, Colorado, United States

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Washington D.C., District of Columbia, United States

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Fort Myers, Florida, United States

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Jacksonville, Florida, United States

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Miami, Florida, United States

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Orlando, Florida, United States

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Lawrenceville, Georgia, United States

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Chicago, Illinois, United States

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Maywood, Illinois, United States

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Niles, Illinois, United States

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Zion, Illinois, United States

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Fort Wayne, Indiana, United States

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Goshen, Indiana, United States

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Indianapolis, Indiana, United States

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Iowa City, Iowa, United States

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Fairway, Kansas, United States

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Baltimore, Maryland, United States

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Bethesda, Maryland, United States

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Boston, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Detroit, Michigan, United States

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Minneapolis, Minnesota, United States

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Rochester, Minnesota, United States

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Springfield, Missouri, United States

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St Louis, Missouri, United States

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Lincoln, Nebraska, United States

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Omaha, Nebraska, United States

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Las Vegas, Nevada, United States

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Basking Ridge, New Jersey, United States

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Hackensack, New Jersey, United States

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Morristown, New Jersey, United States

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Albuquerque, New Mexico, United States

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Albany, New York, United States

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Commack, New York, United States

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New York, New York, United States

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Rochester, New York, United States

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Rockville Centre, New York, United States

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The Bronx, New York, United States

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Charlotte, North Carolina, United States

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Raleigh, North Carolina, United States

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Bismarck, North Dakota, United States

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Cincinnati, Ohio, United States

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Columbus, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Eugene, Oregon, United States

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Hershey, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Charleston, South Carolina, United States

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Greenville, South Carolina, United States

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Chattanooga, Tennessee, United States

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Knoxville, Tennessee, United States

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Nashville, Tennessee, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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San Antonio, Texas, United States

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Tyler, Texas, United States

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Salt Lake City, Utah, United States

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Fairfax, Virginia, United States

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Richmond, Virginia, United States

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Kennewick, Washington, United States

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Seattle, Washington, United States

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Vancouver, Washington, United States

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Yakima, Washington, United States

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Morgantown, West Virginia, United States

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Milwaukee, Wisconsin, United States

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Kingswood, New South Wales, Australia

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St Leonards, New South Wales, Australia

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Westmead, New South Wales, Australia

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South Brisbane, Queensland, Australia

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Bedford Park, South Australia, Australia

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Hobart, Tasmania, Australia

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East Melbourne, Victoria, Australia

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Geelong, Victoria, Australia

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Heidelberg, Victoria, Australia

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Parkville, Victoria, Australia

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Perth, Western Australia, Australia

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Antwerp, , Belgium

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Bruges, , Belgium

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Ghent, , Belgium

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Salvador, Estado de Bahia, Brazil

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Curitiba, Paraná, Brazil

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Porto Alegre, Rio Grande do Sul, Brazil

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Santo André, São Paulo, Brazil

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Rio de Janeiro, , Brazil

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São Paulo, , Brazil

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Edmonton, Alberta, Canada

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Vancouver, British Columbia, Canada

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Winnipeg, Manitoba, Canada

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Halifax, Nova Scotia, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Saskatoon, Saskatchewan, Canada

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Hradec Králové, , Czechia

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Prague, , Czechia

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Aalborg, , Denmark

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Aarhus C, , Denmark

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Copenhagen, , Denmark

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Odense C, , Denmark

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Roskilde, , Denmark

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Argenteuil, Cedex, France

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La Tronche, , France

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Limoges, , France

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Paris, , France

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Lai Chi Kok, Kowloon, Hong Kong

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Hong Kong, , Hong Kong

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Tuenmen, , Hong Kong

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Budapest, , Hungary

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Debrecen, , Hungary

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Győr, , Hungary

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Pécs, , Hungary

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Szeged, , Hungary

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Modena, Emilia-Romagna, Italy

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Rome, Lazio, Italy

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Alessandria, , Italy

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Bologna, , Italy

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Cagliari, , Italy

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Cuneo, , Italy

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Genova, , Italy

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Milan, , Italy

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Napoli, , Italy

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Rionero in Volture, , Italy

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Rome, , Italy

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Rozzano, , Italy

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Torrette Di Ancona, , Italy

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Higashiku, Fukuoka, Japan

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Minamiku, Fukuoka-city, Japan

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Minamiku, Hiroshima-city, Japan

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Shōwamachi, Maebashi-city, Japan

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Chikusa-ku, Nagoya, Japan

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Suita, Osaka, Japan

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Aoba-ku, Sendai-city, Japan

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Chūōku, , Japan

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Isehara-shi, , Japan

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Kōtoku, , Japan

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Bergen, , Norway

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Oslo, , Norway

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Gdansk, , Poland

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Katowice, , Poland

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Krakow, , Poland

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L0dz, , Poland

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Olsztyn, , Poland

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Warsaw, , Poland

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Wroclaw, , Poland

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Ufa, Bashkortostan Republic, Russia

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Saint Petersburg, Poselok Pesochny, Russia

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Kazan', Republic Tatrstan, Russia

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Moscow, , Russia

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Moskva, , Russia

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Saint Petersburg, , Russia

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Johannesburg, Gauteng, South Africa

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Pretoria, Gauteng, South Africa

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eManzimtoti, KwaZulu-Natal, South Africa

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Bloemfontein, , South Africa

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Cape Town, , South Africa

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Goyang-si, Gyeonggi-do, South Korea

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Hwasun-gun, Jeollanam-do, South Korea

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Seocho-gu, Seoul, South Korea

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Busan, , South Korea

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Daegu, , South Korea

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Incheon, , South Korea

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Jeonju, , South Korea

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Seoul, , South Korea

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Badalona, , Spain

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Barcelona, , Spain

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Marbella, , Spain

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Pamplona, , Spain

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Salamanca, , Spain

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Santiago de Compostela, , Spain

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Valencia, , Spain

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Changhua, , Taiwan

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Chiayi County 613, , Taiwan

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Tainan, , Taiwan

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Taipei, , Taiwan

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Taoyuan, , Taiwan

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Ankara, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Samsun, , Turkey (Türkiye)

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Truro, Cornwall, United Kingdom

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Aberdeen, Scotland, United Kingdom

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Glasgow, Scotland, United Kingdom

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Sutton, Surrey, United Kingdom

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Cardiff, Wales, United Kingdom

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Birmingham, , United Kingdom

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Canterbury, , United Kingdom

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Exeter, , United Kingdom

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Inverness, , United Kingdom

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Leicester, , United Kingdom

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Lincoln, , United Kingdom

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Liverpool, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Norfolk, , United Kingdom

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Northwood, , United Kingdom

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Nottingham, , United Kingdom

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Oxford, , United Kingdom

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Romford, , United Kingdom

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Southampton, , United Kingdom

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Countries

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United States Australia Belgium Brazil Canada Czechia Denmark France Hong Kong Hungary Italy Japan Norway Poland Russia South Africa South Korea Spain Taiwan Turkey (Türkiye) United Kingdom

References

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Kreuzberger N, Goldkuhle M, von Tresckow B, Kobe C, Sickinger MT, Monsef I, Skoetz N. Positron emission tomography-adapted therapy for first-line treatment in adults with Hodgkin lymphoma. Cochrane Database Syst Rev. 2025 Mar 26;3(3):CD010533. doi: 10.1002/14651858.CD010533.pub3.

Reference Type DERIVED
PMID: 40135712 (View on PubMed)

Crosswell HE, LaCasce AS, Bartlett NL, Straus DJ, Savage KJ, Zinzani PL, Collins GP, Fanale M, Fenton K, Dong C, Miao H, Grigg AP. Brentuximab vedotin with chemotherapy in adolescents and young adults with stage III or IV classical Hodgkin lymphoma in ECHELON-1. Haematologica. 2024 Mar 1;109(3):982-987. doi: 10.3324/haematol.2023.283303. No abstract available.

Reference Type DERIVED
PMID: 37794803 (View on PubMed)

Ansell SM, Radford J, Connors JM, Dlugosz-Danecka M, Kim WS, Gallamini A, Ramchandren R, Friedberg JW, Advani R, Hutchings M, Evens AM, Smolewski P, Savage KJ, Bartlett NL, Eom HS, Abramson JS, Dong C, Campana F, Fenton K, Puhlmann M, Straus DJ; ECHELON-1 Study Group. Overall Survival with Brentuximab Vedotin in Stage III or IV Hodgkin's Lymphoma. N Engl J Med. 2022 Jul 28;387(4):310-320. doi: 10.1056/NEJMoa2206125. Epub 2022 Jul 13.

Reference Type DERIVED
PMID: 35830649 (View on PubMed)

Evens AM, Connors JM, Younes A, Ansell SM, Kim WS, Radford J, Feldman T, Tuscano J, Savage KJ, Oki Y, Grigg A, Pocock C, Dlugosz-Danecka M, Fenton K, Forero-Torres A, Liu R, Jolin H, Gautam A, Gallamini A. Older patients (aged >/=60 years) with previously untreated advanced-stage classical Hodgkin lymphoma: a detailed analysis from the phase III ECHELON-1 study. Haematologica. 2022 May 1;107(5):1086-1094. doi: 10.3324/haematol.2021.278438.

Reference Type DERIVED
PMID: 34162178 (View on PubMed)

Straus DJ, Dlugosz-Danecka M, Connors JM, Alekseev S, Illes A, Picardi M, Lech-Maranda E, Feldman T, Smolewski P, Savage KJ, Bartlett NL, Walewski J, Ramchandren R, Zinzani PL, Hutchings M, Munoz J, Lee HJ, Kim WS, Advani R, Ansell SM, Younes A, Gallamini A, Liu R, Little M, Fenton K, Fanale M, Radford J. Brentuximab vedotin with chemotherapy for stage III or IV classical Hodgkin lymphoma (ECHELON-1): 5-year update of an international, open-label, randomised, phase 3 trial. Lancet Haematol. 2021 Jun;8(6):e410-e421. doi: 10.1016/S2352-3026(21)00102-2.

Reference Type DERIVED
PMID: 34048680 (View on PubMed)

Straus DJ, Dlugosz-Danecka M, Alekseev S, Illes A, Picardi M, Lech-Maranda E, Feldman T, Smolewski P, Savage KJ, Bartlett NL, Walewski J, Ramchandren R, Zinzani PL, Hutchings M, Connors JM, Radford J, Munoz J, Kim WS, Advani R, Ansell SM, Younes A, Miao H, Liu R, Fenton K, Forero-Torres A, Gallamini A. Brentuximab vedotin with chemotherapy for stage III/IV classical Hodgkin lymphoma: 3-year update of the ECHELON-1 study. Blood. 2020 Mar 5;135(10):735-742. doi: 10.1182/blood.2019003127.

Reference Type DERIVED
PMID: 31945149 (View on PubMed)

Ramchandren R, Advani RH, Ansell SM, Bartlett NL, Chen R, Connors JM, Feldman T, Forero-Torres A, Friedberg JW, Gopal AK, Gordon LI, Kuruvilla J, Savage KJ, Younes A, Engley G, Manley TJ, Fenton K, Straus DJ. Brentuximab Vedotin plus Chemotherapy in North American Subjects with Newly Diagnosed Stage III or IV Hodgkin Lymphoma. Clin Cancer Res. 2019 Mar 15;25(6):1718-1726. doi: 10.1158/1078-0432.CCR-18-2435. Epub 2019 Jan 7.

Reference Type DERIVED
PMID: 30617130 (View on PubMed)

Connors JM, Jurczak W, Straus DJ, Ansell SM, Kim WS, Gallamini A, Younes A, Alekseev S, Illes A, Picardi M, Lech-Maranda E, Oki Y, Feldman T, Smolewski P, Savage KJ, Bartlett NL, Walewski J, Chen R, Ramchandren R, Zinzani PL, Cunningham D, Rosta A, Josephson NC, Song E, Sachs J, Liu R, Jolin HA, Huebner D, Radford J; ECHELON-1 Study Group. Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma. N Engl J Med. 2018 Jan 25;378(4):331-344. doi: 10.1056/NEJMoa1708984. Epub 2017 Dec 10.

Reference Type DERIVED
PMID: 29224502 (View on PubMed)

Younes A, Connors JM, Park SI, Fanale M, O'Meara MM, Hunder NN, Huebner D, Ansell SM. Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin's lymphoma: a phase 1, open-label, dose-escalation study. Lancet Oncol. 2013 Dec;14(13):1348-56. doi: 10.1016/S1470-2045(13)70501-1. Epub 2013 Nov 15.

Reference Type DERIVED
PMID: 24239220 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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C25003

Identifier Type: -

Identifier Source: org_study_id

2011-005450-60

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1161-4937

Identifier Type: REGISTRY

Identifier Source: secondary_id

12/LO/1950

Identifier Type: REGISTRY

Identifier Source: secondary_id

JapicCTI-142491

Identifier Type: REGISTRY

Identifier Source: secondary_id

REec-2013-0114

Identifier Type: REGISTRY

Identifier Source: secondary_id

1025002760

Identifier Type: REGISTRY

Identifier Source: secondary_id

C25003CTID

Identifier Type: OTHER

Identifier Source: secondary_id

2023-506419-16-00

Identifier Type: CTIS

Identifier Source: secondary_id