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NCT05139017PHASE2, PHASE3Recruiting

A Study of Zilovertamab Vedotin (MK-2140) in Combination With Standard of Care in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (rrDLBCL) (MK-2140-003)

Merck Sharp & Dohme LLC

Start Date

1/14/2022

Completion Date

9/24/2027

Summary

The purpose of this Phase 2/3, randomized, multisite, open-label, dose confirmation, and expansion study is to evaluate the safety, and efficacy of zilovertamab vedotin (ZV) in combination with standard of care options for the treatment of rrDLBCL. This study will be divided into 2 parts: Dose Confirmation (Part 1) and Efficacy Expansion (Part 2) and will enroll participants who are at least 18 years of age with rrDLBCL. The hypotheses are: ZV in combination with rituximab, gemcitabine, and oxaliplatin (R-GemOx) is superior to R-GemOx with respect to progression-free survival (PFS) per Lugano response criteria by blinded independent review committee (BICR); and that ZV in combination with bendamustine rituximab (BR) is superior to BR with respect to PFS per Lugano response criteria by BICR. With protocol amendment 4 (effective: 04-April-2024), enrollment in Cohort B (study arms Bendamustine Rituximab \[BR\] and ZV + BR) is discontinued. No efficacy outcome analysis and hypothesis testing will be conducted for Cohort B.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * Has a histologically confirmed diagnosis of Diffuse Large B-Cell Lymphoma (DLBCL). * Has radiographically measurable DLBCL per the Lugano Response Criteria, as assessed locally by the investigator. * Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 within 7 days prior to study treatment initiation. * Has adequate organ function. * Is able to provide new or archival tumor tissue sample not previously irradiated. Zilovertamab vedotin plus R-GemOx, or R-GemOx study arms: * Has relapsed or refractory DLBCL and is ineligible for or have failed autologous stem-cell transplant (ASCT) and have failed at least 1 line of prior therapy. * Has post-chimeric antigen receptor T (post-CAR-T) cell therapy failure or is ineligible for CAR-T cell therapy. Not applicable with protocol amendment 4: Zilovertamab vedotin plus Bendamustine Rituximab (BR), and Bendamustine Rituximab study arms: * Has relapsed or refractory DLBCL and is ineligible for or have failed ASCT and have failed at least 2 lines of prior therapy. * Has post-CAR-T therapy failure or is ineligible for CAR-T cell therapy. Exclusion Criteria: * Not applicable with protocol amendment 4: Has history of transformation of indolent disease to DLBCL * Has received solid organ transplant at any time. * Has received a diagnosis of primary mediastinal B-cell lymphoma (PMBCL). * Has clinically significant (ie, active) cardiovascular disease or serious cardiac arrhythmia requiring medication. * Has ongoing graft-versus-host disease (GVHD) of any grade, or is receiving treatment for their GVHD. * Has clinically significant pericardial or pleural effusion. * Has ongoing Grade \>1 peripheral neuropathy. * Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. * Has a demyelinating form of Charcot-Marie-Tooth disease. * Has contraindication to any of the study intervention components including but not limited to prior anaphylactic reaction. * Has received prior systemic anticancer therapy, including investigational agents within 4 weeks prior to the first dose of study intervention. * Has received prior radiotherapy within 4 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. * Has ongoing corticosteroid therapy. * Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. * Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention. * Has known active central nervous system (CNS) lymphoma involvement or active CNS involvement by lymphoma. Participants with prior CNS involvement are eligible if their CNS disease is in radiographic, cytological (for cerebrospinal fluid disease), and clinical remission. * Has an active infection requiring systemic therapy. * Has a known history of human immunodeficiency virus (HIV) infection. * Has a known active Hepatitis C virus infection. * Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.

Interventions

BIOLOGICAL

Zilovertamab vedotin

BIOLOGICAL

Rituximab

DRUG

Gemcitabine

DRUG

Oxaliplatin

DRUG

Bendamustine

DRUG

Granulocyte Colony-Stimulating Factor (G-CSF)

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Conditions

DLBCLDiffuse Large B-Cell Lymphoma

Locations

Palo Verde Hematology/ Oncology Center, Ltd. ( Site 0175)

Glendale, Arizona 85304

United States

Beverly Hills Cancer Center ( Site 0184)

Beverly Hills, California 90211

United States

Bass Medical Group ( Site 0166)

Walnut Creek, California 94598

United States

Innovative Clinical Research Institute ( Site 0122)

Whittier, California 90603

United States

Boca Raton Regional Hospital- Lynn Cancer Institute ( Site 0163)

Boca Raton, Florida 33486

United States

Clermont Oncology Center ( Site 0174)

Clermont, Florida 34711

United States

BRP-Hialeah Hospital ( Site 0182)

Hialeah, Florida 33013

United States

Illinois Cancer Specialists ( Site 8000)

Niles, Illinois 60714

United States

Saint Elizabeth Medical Center Edgewood ( Site 0165)

Edgewood, Kentucky 41017

United States

University of Kentucky Chandler Medical Center ( Site 0158)

Lexington, Kentucky 40536

United States

Norton Women's and Children's Hospital-Norton Cancer Institute - St. Matthews ( Site 0133)

Louisville, Kentucky 40207

United States

University of Maryland ( Site 0123)

Baltimore, Maryland 21201

United States

Dana-Farber Cancer Institute-Lymphoma ( Site 0111)

Boston, Massachusetts 02215

United States

University of Massachusetts Medical School ( Site 0119)

Worcester, Massachusetts 01655

United States

Corewell Health ( Site 0162)

Grand Rapids, Michigan 49503

United States

St. Vincent Frontier Cancer Center-Research ( Site 0108)

Billings, Montana 59102

United States

Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0188)

Grand Island, Nebraska 68803

United States

Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0177)

Omaha, Nebraska 68130

United States

Comprehensive Cancer Centers of Nevada ( Site 0168)

Las Vegas, Nevada 89169

United States

Atlantic Health System ( Site 0116)

Morristown, New Jersey 07960

United States

Presbyterian Rust Jorgensen Cancer ( Site 9506)

Rio Rancho, New Mexico 87124

United States

New York Medical College ( Site 0113)

Valhalla, New York 10595

United States

Alliance Cancer Specialists (ACS) ( Site 8001)

Horsham, Pennsylvania 19044

United States

Tennessee Cancer Specialists ( Site 7000)

Knoxville, Tennessee 37909

United States

Vanderbilt University Medical Center-Vanderbilt-Ingram Cancer Center ( Site 0156)

Nashville, Tennessee 37232

United States

Blue Ridge Cancer Care ( Site 0169)

Roanoke, Virginia 24014

United States

Hospital Italiano de Buenos Aires ( Site 2203)

Ciudad Autonoma de Buenos Aires, Buenos Aires C1199ABB

Argentina

Instituto de Investigaciones Clínicas Mar del Plata ( Site 2205)

Mar del Plata, Buenos Aires B7600FZO

Argentina

Hospital Aleman ( Site 2200)

Buenos Aites, Buenos Aires F.D. C1118AAT

Argentina

Hospital Privado Universitario de Córdoba ( Site 2202)

Córdoba, Córdoba Province X5016KEH

Argentina

Instituto Alexander Fleming ( Site 2201)

CABA, C1426ANZ

Argentina

Townsville University Hospital ( Site 1800)

Townsville, Queensland 4814

Australia

Grampians Health ( Site 1802)

Ballarat, Victoria 3350

Australia

Royal Perth Hospital-Haematology ( Site 1801)

Perth, Western Australia 6000

Australia

Hospital Erasto Gaertner ( Site 2302)

Curitiba, Paraná 81520-060

Brazil

Liga Norte Riograndense Contra o Câncer ( Site 2305)

Natal, Rio Grande do Norte 59062-000

Brazil

Hospital Paulistano ( Site 2300)

São Paulo, 01321-001

Brazil

Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0200)

Toronto, Ontario M5G 2M9

Canada

Biocenter ( Site 2401)

Concepción, Biobio 4070196

Chile

IC La Serena Research ( Site 2405)

La Serena, Coquimbo Region 1720430

Chile

Oncocentro Valdivia ( Site 2407)

Valdivia, Los Ríos Region 5112129

Chile

FALP-UIDO ( Site 2400)

Santiago, Region M. de Santiago 7500921

Chile

Clínica Inmunocel ( Site 2404)

Santiago, Region M. de Santiago 7580206

Chile

Clínica RedSalud Vitacura ( Site 2409)

Santiago, Region M. de Santiago 7650018

Chile

Bradfordhill ( Site 2403)

Santiago, Region M. de Santiago 8420383

Chile

Beijing Cancer hospital ( Site 3000)

Beijing, Beijing Municipality 100142

China

Chongqing University Cancer Hospital-Medical Oncology ( Site 3025)

Chongqing, Chongqing Municipality 400030

China

Chongqing University Three Gorges Hospital ( Site 3026)

Chongqing, Chongqing Municipality 404199

China

Sun Yat-sen University Cancer Center-Internal Medicine ( Site 3001)

Guangzhou, Guangdong 510060

China

Zhujiang Hospital ( Site 3002)

Guangzhou, Guangdong 510280

China

The First Affiliated Hospital of Henan University of Science &Technology ( Site 3029)

Luoyang, Henan 471003

China

Henan Cancer Hospital-hematology department ( Site 3013)

Zhengzhou, Henan 450008

China

Union Hospital Tongji Medical College Huazhong University of Science and Technology ( Site 3017)

Wuhan, Hubei 430048

China

The First Affiliated Hospital of Nanchang University ( Site 3004)

Nanchang, Jiangxi 330006

China

Jiangxi Provincial Cancer Hospital ( Site 3005)

Nanchang, Jiangxi 330029

China

The First Hospital of Jilin University-Hematology ( Site 3012)

Changchun, Jilin 130021

China

Fudan University Shanghai Cancer Center ( Site 3009)

Shanghai, Shanghai Municipality 200032

China

Sichuan Cancer hospital-Oncology ( Site 3021)

Chengdu, Sichuan 610041

China

West China Hospital of Sichuan University-Head and Neck Oncology ( Site 3016)

Chengdu, Sichuan 610041

China

Zhejiang Cancer Hospital ( Site 3014)

Hangzhou, Zhejiang 310000

China

The First Affiliated Hospital Zhejiang University School of Medicine ( Site 3027)

Hangzhou, Zhejiang 310003

China

Hospital Pablo Tobon Uribe ( Site 0804)

Medellín, Antioquia 50034

Colombia

FUNDACION CTIC CENTRO DE TRATAMIENTO E INVESTIGACION SOBRE CANCER LUIS CARLOS SARMIENTO ANGULO ( Site 0801)

Bogotá, Bogota D.C. 110131

Colombia

Instituto Médico de Alta Tecnologia S.A.S ( Site 0803)

Montería, Departamento de Córdoba 230002

Colombia

Oncologos del Occidente ( Site 0800)

Pereira, Risaralda Department 660001

Colombia

Fundacion Valle del Lili ( Site 0802)

Cali, Valle del Cauca Department 760032

Colombia

Hospital Metropolitano - Sede Lindora ( Site 2500)

Santa Ana, Provincia de San José 10903

Costa Rica

CIMCA ( Site 2501)

San José, 10103

Costa Rica

Aarhus Universitetshospital, Skejby ( Site 1701)

Aarhus, Central Jutland 8200

Denmark

centre hospitalier lyon sud-Service Hématologie ( Site 0702)

Pierre-Bénite, Rhone 69310

France

Pitie Salpetriere University Hospital-Clinical haematology ( Site 0700)

Paris, 75013

France

Evangelismos General Hospital of Athens ( Site 0900)

Athens, Attica 106 76

Greece

Regional General Hospital of Athens "Laiko" ( Site 0901)

Athens, Attica 115 26

Greece

University Hospital of Alexandroupolis ( Site 0903)

Alexandroupoli, East Macedonia and Thrace 681 00

Greece

MEDI-K ( Site 2602)

Guatemala City, 01009

Guatemala

Private Practice- Dr. Rixci Augusto Lenin Ramírez ( Site 2601)

Guatemala City, 01010

Guatemala

CELAN,S.A ( Site 2603)

Guatemala City, 1010

Guatemala

Queen Mary Hospital ( Site 3100)

Hong Kong, 000000

Hong Kong

Princess Margaret Hospital ( Site 3101)

Hong Kong,

Hong Kong

Emek Medical Center-Hematology Unit ( Site 1102)

Afula, 1834111

Israel

Carmel Hospital ( Site 1103)

Haifa, 3436212

Israel

Hadassah Medical Center ( Site 1100)

Jerusalem, 9112001

Israel

Humanitas-U.O di Oncologia medica ed Ematologia ( Site 1203)

Rozzano, Milano 20089

Italy

IRCCS - AOU di Bologna-Istituto di Ematologia "L. e A. Seragnoli" ( Site 1200)

Bologna, 40138

Italy

Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1202)

Naples, 80131

Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS -ISTITUTO DI EMATOLOGIA ( Site 1204)

Roma, 00168

Italy

Hokkaido University Hospital ( Site 3202)

Sapporo, Hokkaido 060-8648

Japan

Tokai University Hospital ( Site 3212)

Isehara, Kanagawa 259-1193

Japan

Mie University Hospital ( Site 3210)

Tsu, Mie-ken 514-8507

Japan

Kansai Medical University Hospital ( Site 3203)

Hirakata, Osaka 573-1191

Japan

Tokyo Metropolitan Komagome Hospital ( Site 3200)

Bunkyo, Tokyo 113-8677

Japan

The Jikei University Hospital ( Site 3208)

Minato, Tokyo 105-8471

Japan

University of Yamanashi Hospital ( Site 3201)

Chūō, Yamanashi 409-3898

Japan

National Hospital Organization Kyushu Cancer Center ( Site 3204)

Fukuoka, 811-1395

Japan

Fukushima Medical University Hospital ( Site 3207)

Fukushima, 960-1295

Japan

University Hospital,Kyoto Prefectural University of Medicine ( Site 3209)

Kyoto, 602-8566

Japan

University of Miyazaki Hospital ( Site 3211)

Miyazaki, 889-1692

Japan

Osaka Metropolitan University Hospital ( Site 3205)

Osaka, 545-8586

Japan

Yamagata University Hospital ( Site 3206)

Yamagata, 990-9585

Japan

Health Pharma Professional Research S.A. de C.V: ( Site 2700)

Mexico City, Mexico City 03100

Mexico

Medivest Centro de Investigación Integral ( Site 2704)

Chihuahua City, 31203

Mexico

Centro de Infusion Superare ( Site 2701)

Mexico City, 03104

Mexico

Aotearoa Clinical Trials ( Site 0501)

Auckland, 2025

New Zealand

Clínicas AUNA Sede Chiclayo ( Site 2803)

Chiclayo, Lambayeque 14001

Peru

INSTITUTO NACIONAL DE ENFERMEDADES NEOPLASICAS ( Site 2800)

Surquillo, Muni Metro de Lima 15038

Peru

Clínica San Felipe ( Site 2805)

Lima, 15072

Peru

Hospital Nacional Edgardo Rebagliati Martins ( Site 2802)

Lima, 15072

Peru

Hospital Nacional Dos De Mayo ( Site 2804)

Lima, 15087

Peru

Pratia MCM Krakow ( Site 1303)

Krakow, Lesser Poland Voivodeship 30-727

Poland

Specjalistyczny Szpital im. Dr Alfreda Sokolowskiego w Walbrzychu ( Site 1305)

Wałbrzych, Lower Silesian Voivodeship 58-309

Poland

Uniwersytecki Szpital Kliniczny-Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku ( Site 1301)

Wroclaw, Lower Silesian Voivodeship 50-367

Poland

Centrum Onkologii Ziemi Lubelskiej-Oddzial Hematologii i Transplantacji Szpiku ( Site 1304)

Lublin, Lublin Voivodeship 20-090

Poland

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworów Układu Chłonnego ( Site 1300)

Warsaw, Masovian Voivodeship 02-781

Poland

Szpitale Pomorskie Sp. z o. o.-Hematology and Bone Marrow Transplantation Department ( Site 1302)

Gdynia, Pomeranian Voivodeship 81-519

Poland

Wojewódzki Szpital Specjalistyczny im. J. Korczaka w Słupsku ( Site 1309)

Słupsk, Pomeranian Voivodeship 76-200

Poland

Pratia Onkologia Katowice ( Site 1306)

Katowice, Silesian Voivodeship 40-519

Poland

Seoul National University Hospital-Oncology ( Site 0302)

Seoul, 03080

South Korea

Samsung Medical Center ( Site 0300)

Seoul, 06351

South Korea

Faculty of Medicine Siriraj Hospital-Division of Hematology, Department of Medicine ( Site 0400)

Bangkok, Bangkok 10700

Thailand

Chulalongkorn University ( Site 0402)

Pathumwan, Bangkok 10330

Thailand

Maharaj Nakorn Chiang Mai Hospital ( Site 0401)

Chiang Mai, 50200

Thailand

Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastırma Hastanesi ( Site 1912)

Yenimahalle, Ankara 06200

Turkey (Türkiye)

Ege University Medicine of Faculty ( Site 1902)

Bornova, İzmir 35100

Turkey (Türkiye)

Ankara University Hospital Cebeci-hematology ( Site 1901)

Ankara, 06100

Turkey (Türkiye)

Mega Medipol-Hematology ( Site 1909)

Istanbul, 34214

Turkey (Türkiye)

Dokuz Eylül Üniversitesi-Hematology ( Site 1905)

Izmir, 35340

Turkey (Türkiye)

Ondokuz Mayıs Universitesi ( Site 1907)

Samsun, 55139

Turkey (Türkiye)

MNPE ClinCenter of Oncology,Hematology,Transplantology and Palliative Care of CherkasyRegCouncil ( Site 2000)

Cherkasy, Cherkasy Oblast 18009

Ukraine

Communal non-profit enterprise "Regional clinical hospital of Ivano-Frankivsk Regional Council" ( Site 2004)

Ivano-Frankivsk, Ivano-Frankivsk Oblast 76008

Ukraine

Institute of Blood Pathology and Transfusion Medicine AMS Ukraine ( Site 2002)

Lviv, Lviv Oblast 79057

Ukraine

State non-profit enterprise National Cancer Institute ( Site 2001)

Kyiv, 03022

Ukraine

National Research Center for Radiation Medicine of National Academy of Medical Sciences of Ukraine ( Site 2005)

Kyiv, 03115

Ukraine

Aberdeen Royal Infirmary ( Site 2104)

Aberdeen, Aberdeen City AB25 2ZN

United Kingdom

The Royal Cornwall Hospital ( Site 2103)

Truro, England TR1 3LJ

United Kingdom

University College London Hospital-Cancer Clinical Trials Unit ( Site 2100)

London-Camden, London, City of NW1 2PG

United Kingdom