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

Study Description

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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
Hodgkin Lymphoma	Drug: brentuximab vedotin; Drug: doxorubicin; Drug: bleomycin; Drug: vinblastine; Drug: dacarbazine	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
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 :	November 1, 2012
Actual Primary Completion Date :	April 20, 2017
Estimated Study Completion Date :	March 1, 2020

Arms and Interventions

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Arm	Intervention/treatment
Experimental: A + AVD; A+AVD consists of brentuximab vedotin (ADCETRIS®) 1.2 mg/kg plus doxorubicin 25 mg/m2, vinblastine 6 mg/m2, and dacarbazine (DTIC) 375 mg/m2	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/m2 by IV infusion on Days 1 and 15 of each 28-day cycle; Other Name: 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/m2 by IV infusion on Days 1 and 15 of each 28-day cycle; Other Name: DTIC
Active Comparator: ABVD; ABVD consists of doxorubicin 25 mg/m2, bleomycin 10 units/m2, vinblastine 6 mg/m2, and dacarbazine (DTIC) 375 mg/m2	Drug: doxorubicin; Doxorubicin: 25 mg/m2 by IV infusion on Days 1 and 15 of each 28-day cycle; Other Name: Adriamycin Drug: bleomycin; Bleomycin: 10 units/m2 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/m2 by IV infusion on Days 1 and 15 of each 28-day cycle; Other Name: DTIC

Outcome Measures

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Modified progression free survival (mPFS) per independent review facility (IRF) [ Time Frame: Date of randomization to mPFS event, for approximately 3 to 5 years ]

Secondary Outcome Measures :

1. Overall survival rate [ Time Frame: Date of randomization to the date of death, for approximately 5 to 7 years ]
   Date of randomization to the date of death

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Treatment-naïve
• Histologically confirmed classical Hodgkin Lymphoma (HL)
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Bidimensional measurable disease

Exclusion Criteria:

• Nodular lymphocyte predominant Hodgkin lymphoma
• Cerebral/meningeal disease, including signs and symptoms of progressive multifocal leukoencephalopathy (PML)
• Pulmonary diffusion capacity > 25% lower than normal predicted value
• Sensory or motor peripheral neuropathy
• Known human immunodeficiency virus (HIV) positive
• 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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

  Show 216 Study Locations

Sponsors and Collaborators

Millennium Pharmaceuticals, Inc.

Seattle Genetics, Inc.

Investigators

Study Director:	Medical Monitor	Millennium Pharmaceuticals, Inc.

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Related Info 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Connors JM, Jurczak W, Straus DJ, Ansell SM, Kim WS, Gallamini A, Younes A, Alekseev S, Illés Á, 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. Erratum in: N Engl J Med. 2018 Mar 1;378(9):878.

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.

Responsible Party:	Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT01712490 History of Changes
Other Study ID Numbers:	C25003; 2011-005450-60 ( EudraCT Number ); U1111-1161-4937 ( Registry Identifier: WHO ); 12/LO/1950 ( Registry Identifier: NRES ); JapicCTI-142491 ( Registry Identifier: JapicCTI ); REec-2013-0114 ( Registry Identifier: REec ); 1025002760 ( Registry Identifier: TCTIN ); C25003CTID ( Other Identifier: Israel )
First Posted:	October 23, 2012
Last Update Posted:	August 1, 2017
Last Verified:	July 2017

Keywords provided by Takeda ( Millennium Pharmaceuticals, Inc. ):

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; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Antibodies; Antibodies, Monoclonal; Doxorubicin; Liposomal doxorubicin; Bleomycin	Vinblastine; Immunologic Factors; Physiological Effects of Drugs; Antibiotics, Antineoplastic; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Phytogenic; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators