MedPath

Brentuximab Vedotin Plus Lenalidomide and Rituximab for the Treatment of Relapsed/Refractory DLBCL

Phase 3
Active, not recruiting
Conditions
Diffuse Large B-cell Lymphoma
Interventions
Registration Number
NCT04404283
Lead Sponsor
Seagen, a wholly owned subsidiary of Pfizer
Brief Summary

Participants in this study will have diffuse large B-cell lymphoma (DLBCL) that has come back or not gotten better with treatment. The trial will study whether brentuximab vedotin plus two drugs works better to treat this type of cancer than the two drugs alone.

Participants will be randomly assigned to get either brentuximab vedotin or placebo. The placebo will look like brentuximab vedotin, but has no medicine in it. Since the study is "blinded," participants and their doctors will not know whether a participant gets brentuximab vedotin or placebo. All participants in the study will get rituximab and lenalidomide. These are drugs that can be used to treat DLBCL.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
241
Inclusion Criteria
  • Participants with relapsed or refractory diffuse and transformed large B-cell lymphoma (R/R DLBCL). DLBCL and cell of origin (GCB versus non-GCB) will be histologically determined by local pathology assessment for the purposes of study eligibility and stratification.

  • Participants must have R/R disease following 2 or more lines of prior systemic therapy.

    • For participants with transformed DLBCL, at least the last systemic therapy used must have been for DLBCL
  • Participants must be HSCT or CAR-T ineligible according to the investigator and must meet at least one of the following criteria:

    1. One or more co-morbidities, including cardiac, pulmonary, renal or hepatic dysfunction that in the opinion of the Investigator make the participant medically unfit to received HSCT or CAR-T therapy
    2. Active disease following induction and salvage chemotherapy
    3. Inadequate stem cell mobilization (for HSCT)
    4. Relapse following prior HSCT or CAR-T
    5. Unable to receive CAR-T therapy due to financial, geographic, insurance, or manufacturing issues
  • Participants must have tumor tissue submitted to the central pathology lab. The tumor tissue submitted should be from the most recent biopsy that contains DLBCL.

  • An Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2

  • Participants must have fluorodeoxyglucose (FDG)-avid disease by positron emission tomography (PET) and bidimensional measurable disease of at least 1.5 cm by computed tomography (CT), as assessed by the site radiologist within 28 days of Day 1.

Exclusion Criteria
  • History of another malignancy within 2 years before the first dose of study drug or any evidence of residual disease from a previously diagnosed malignancy

  • History of progressive multifocal leukoencephalopathy (PML)

  • Active cerebral/meningeal disease related to the underlying malignancy. Participants with a history of cerebral/meningeal disease related to the underlying malignancy are allowed if prior CNS disease has been effectively treated and without progression for at least 3 months.

  • Any uncontrolled Grade 3 or higher (per NCI CTCAE version 5.0) viral, bacterial, or fungal infection within 2 weeks prior to the first dose of study drug. Routine antimicrobial prophylaxis is permitted

  • Chemotherapy, radiotherapy, biologics, and/or other antitumor treatment with immunotherapy that is not completed 3 weeks prior to first dose of study drug, unless underlying disease has progressed on treatment

  • Previous treatment with brentuximab vedotin or lenalidomide.

    • Previous treatment with other vedotin-based ADCs is permitted if the last dose is at least 6 months prior to Day 1.
  • Current therapy with immunosuppressive medications (including steroids), other systemic anti-neoplastic, or investigational agents

    a) Prednisone (or equivalent) ≤10 mg/day may be used for non-lymphomatous purposes

  • Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association (NYHA) Class III-IV within 6 months prior to the first dose of study drugs

  • Congestive heart failure, Class III or IV, by the NYHA criteria

  • Grade 2 or higher peripheral sensory or motor neuropathy at baseline

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Experimental ArmLenalidomideBrentuximab vedotin + lenalidomide + rituximab
Control ArmLenalidomidePlacebo + lenalidomide + rituximab
Control ArmPlaceboPlacebo + lenalidomide + rituximab
Control ArmRituximabPlacebo + lenalidomide + rituximab
Experimental ArmBrentuximab vedotinBrentuximab vedotin + lenalidomide + rituximab
Experimental ArmRituximabBrentuximab vedotin + lenalidomide + rituximab
Primary Outcome Measures
NameTimeMethod
Overall survival (OS)Approximately 2 years

OS is defined as the time from the date of randomization to date of death due to any cause

Secondary Outcome Measures
NameTimeMethod
Progression-free survival (PFS)Approximately 1 year

PFS is defined as the time from the date of randomization to the date of first documentation of progressive disease (PD) or death due to any cause, whichever occurs first. Assessment of PD will be performed by the investigator based on the Lugano Criteria for Response Assessment (Cheson 2014)

Incidence of adverse eventsApproximately 1 year

Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.

OS in CD30+ participantsApproximately 2 years

Time from the date of randomization to date of death due to any cause.

Objective response rate (ORR)Approximately 1 year

Proportion of participants with best response of complete response (CR) or partial response (PR) according to investigator assessment per the Lugano Criteria for Response Assessment (Cheson 2014).

Complete response (CR) rateApproximately 1 year

Proportion of participants with best response of CR according to investigator assessment per the Lugano Criteria for Response Assessment (Cheson 2014)

Duration of response (DOR)Approximately 1 year

Time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of tumor progression by investigator assessment per the Lugano Criteria for Response Assessment (Cheson 2014) or death due to any cause, whichever occurs first.

Trial Locations

Locations (171)

Central Alabama Research

🇺🇸

Birmingham, Alabama, United States

Alabama Oncology

🇺🇸

Birmingham, Alabama, United States

Arizona Oncology Associates, PC - NAHOA

🇺🇸

Goodyear, Arizona, United States

The Oncology Institute of Hope & Innovation - California

🇺🇸

Riverside, California, United States

University of California Davis

🇺🇸

Sacramento, California, United States

Lundquist Institute/Harbor-UCLA

🇺🇸

Torrance, California, United States

Florida Cancer Specialists - South Region

🇺🇸

Fort Myers, Florida, United States

Florida Cancer Specialists - North Region

🇺🇸

Saint Petersburg, Florida, United States

Florida Cancer Specialists - East West Palm Beach, FL (SCRI)

🇺🇸

West Palm Beach, Florida, United States

Rush University Medical Center

🇺🇸

Chicago, Illinois, United States

Illinois Cancer Specialists

🇺🇸

Niles, Illinois, United States

University of Maryland

🇺🇸

Baltimore, Maryland, United States

Karmanos Cancer Institute / Wayne State University

🇺🇸

Detroit, Michigan, United States

Henry Ford Health System

🇺🇸

Detroit, Michigan, United States

Cancer and Hematology Centers of Western Michigan / Lemmen-Holton Cancer Pavilion

🇺🇸

Grand Rapids, Michigan, United States

Ascension St John Hospital

🇺🇸

Grosse Pointe Woods, Michigan, United States

Mayo Clinic Rochester

🇺🇸

Rochester, Minnesota, United States

HCA Midwest Health Kansas City

🇺🇸

Kansas City, Missouri, United States

Saint Louis University

🇺🇸

Saint Louis, Missouri, United States

Washington University in St Louis

🇺🇸

Saint Louis, Missouri, United States

University of Nebraska Medical Center

🇺🇸

Omaha, Nebraska, United States

MD Anderson Cancer Center at Cooper Health

🇺🇸

Camden, New Jersey, United States

Summit Medical Group

🇺🇸

Florham Park, New Jersey, United States

New York Cancer and Blood Specialists

🇺🇸

Shirley, New York, United States

Oncology Hematology Care

🇺🇸

Cincinnati, Ohio, United States

University of Cincinnati Cancer Institute

🇺🇸

Cincinnati, Ohio, United States

Willamette Valley Cancer Institute and Research Center

🇺🇸

Eugene, Oregon, United States

Roper St. Francis Healthcare

🇺🇸

Charleston, South Carolina, United States

Medical University of South Carolina/Hollings Cancer Center

🇺🇸

Charleston, South Carolina, United States

Saint Francis Hospital / Bon Secours - South Carolina

🇺🇸

Greenville, South Carolina, United States

Prisma Health

🇺🇸

Greenville, South Carolina, United States

University of Tennessee

🇺🇸

Knoxville, Tennessee, United States

Texas Oncology - Austin Midtown

🇺🇸

Austin, Texas, United States

Texas Oncology - San Antonio Medical Center

🇺🇸

San Antonio, Texas, United States

University of Virginia

🇺🇸

Charlottesville, Virginia, United States

Northwest Cancer Specialists, P.C.

🇺🇸

Vancouver, Washington, United States

Carbone Cancer Center / University of Wisconsin

🇺🇸

Madison, Wisconsin, United States

Aurora Health Care, Inc

🇺🇸

Wauwatosa, Wisconsin, United States

Royal Adelaide Hospital

🇦🇺

Adelaide, Other, Australia

Central Coast Local Health District (Gosford and Wyong Hospitals)

🇦🇺

Gosford, Other, Australia

Royal Hobart Hospital

🇦🇺

Hobart, Other, Australia

Hollywood Haematology

🇦🇺

Nedlands, Other, Australia

Royal North Shore Hospital

🇦🇺

Saint Leonards, Other, Australia

Ziekenhuis Netwerk Antwerpen Campus Stuivenberg

🇧🇪

Antwerpen, Other, Belgium

Universitair Ziekenhuis Antwerpen

🇧🇪

Edegem, Other, Belgium

Universitair Ziekenhuis Gent

🇧🇪

Gent, Other, Belgium

CHU Helora Hopital de La Louviere Site Jolimont

🇧🇪

Haine-Saint-Paul, Other, Belgium

Clinique Saint Pierre

🇧🇪

Ottignies, Other, Belgium

AZ Delta - Campus Wilgenstraat

🇧🇪

Roeselare, Other, Belgium

CHU UCL Namur

🇧🇪

Yvoir, Other, Belgium

H. Bliss Murphy Cancer Centre / Eastern Regional Health Authority

🇨🇦

St John's, Newfoundland and Labrador, Canada

Queen Elizabeth II Health Sciences Centre

🇨🇦

Halifax, Nova Scotia, Canada

William Osler Health Sciences

🇨🇦

East Brampton, Ontario, Canada

London Health Sciences Centre - Victoria Hospital

🇨🇦

London, Ontario, Canada

Lakeridge Health - The R.S. McLaughlin Durham Regional Cancer Centre (MDRCC)

🇨🇦

Oshawa, Ontario, Canada

University of Ottawa / Ottawa General Hospital

🇨🇦

Ottawa, Ontario, Canada

CISSS de la Monteregie-Centre

🇨🇦

Greenfield Park, Quebec, Canada

CIUSSS de L'Est de l'lle de Montreal / installation Hopital Maisonneuve-Rosemont

🇨🇦

Montreal, Quebec, Canada

CIUSS NIM/Hopital du Sacre-Coeur de Montreal

🇨🇦

Montreal, Quebec, Canada

Fakultni nemocnice Hradec Kralove-oddeleni klinicke hematologie

🇨🇿

Hradec Kralove, Other, Czechia

Fakultni Nemocnice Kralovske Vinohrady

🇨🇿

Praha 10, Other, Czechia

Vseobecna fakultni nemocnice v Praze

🇨🇿

Praha 2, Other, Czechia

Aalborg Universitetshospital

🇩🇰

Aalborg, Other, Denmark

Aarhus University Hospital

🇩🇰

Aarhus N, Other, Denmark

Rigshospitalet

🇩🇰

Copenhagen, Other, Denmark

Zealand University Hospital (Roskilde Sygehus)

🇩🇰

Roskilde, Other, Denmark

Center Hospitalier Universitaire d' Angers

🇫🇷

Angers Cedex 9, Other, France

Centre de Lutte Contre le Cancer (CLCC) - Institut Bergonie

🇫🇷

Bordeaux, Other, France

Centre Hospitalier Regional Universitaire (CHRU) Brest - Hopital Morvan

🇫🇷

Brest Cedex, Other, France

CHD Vendee, Site de La Roche-sur-Yon, Les Oudairies

🇫🇷

Cedex 9, Other, France

Centre Hospitalier Metropole Savoie - Chambery

🇫🇷

Chambery, Other, France

Centre Hospitalier Sud Francilien

🇫🇷

Corbeil-Essonnes, Other, France

Centre Hospitalier Universitaire (CHU) Dijon Bourgogne

🇫🇷

Dijon, Other, France

Centre Hospitalier Universitaire de Grenoble

🇫🇷

Grenoble, Other, France

Centre Hospitalier Le Mans

🇫🇷

Le Mans, Other, France

Centre Hospitalier Universitaire (CHU) De Limoges - Hopital Dupuytren

🇫🇷

Limoges Cedex, Other, France

Centre Leon Berard - Centre regional de lutte contre le cancer Rhone-Alpes

🇫🇷

Lyon, Other, France

Centre Hospitalier Regional Metz-Thionville, Hopital Mercy

🇫🇷

Metz, Other, France

Hopital Emile Muller

🇫🇷

Mulhouse, Other, France

Centre Hospitalier Universitaire Nantes-Hotel Dieu

🇫🇷

Nantes cedex 1, Other, France

Centre de Lutte contre le Cancer (CLCC) - Centre Antoine Lacassagne

🇫🇷

Nice Cedex 2, Other, France

Centre Hospitalier de Perpignan

🇫🇷

Perpignan CEDEX, Other, France

CHU Bordeaux Hopital Haut-Leveque

🇫🇷

Pessac Cedex, Other, France

Centre Hospitalier Lyon Sud

🇫🇷

Pierre-Benite Cedex, Other, France

Centre Henri Becquerel / Centre Regional de Lutte Contre le Cancer

🇫🇷

Rouen, Other, France

Institut de Cancerologie Hematologie Universitaire de Saint Etienne (I.CHU.SE)

🇫🇷

Saint Etienne Cedex 2, Other, France

Centre Hospitalier Universitaire de Nancy - Hopital de Brabois

🇫🇷

Vandoeuvre-Les-Nancy Cedex 9, Other, France

Institut Gustave Roussy

🇫🇷

Villejuif Cedex, Other, France

CHU Tours - Hopital Bretonneau

🇫🇷

Paris, France

Hopital Saint-Antoine

🇫🇷

Paris, France

Medizinische Klinik & Poliklinik III (Bonn)nUniversitätsklinikum Bonn

🇩🇪

Bonn, Other, Germany

Stadtisches Klinikum Brandenburg GmbH

🇩🇪

Brandenburg, Other, Germany

Universitaetsklinikum Dusseldorf

🇩🇪

Duesseldorf, Other, Germany

Universitaetsklinikum Halle (Saale)

🇩🇪

Halle (S.), Other, Germany

Centro di Riferimento Oncologico di Aviano

🇮🇹

Aviano (Pordenone), Other, Italy

IRCCS Istituto Tumori Giovanni Paolo II

🇮🇹

Bari, Other, Italy

Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi

🇮🇹

Bologna, Other, Italy

Azienda Ospedaliero Universitaria Careggi

🇮🇹

Firenze, Other, Italy

Azienda Ospedaliera Universitaria San Martino

🇮🇹

Genova, Other, Italy

Azienda Ospedaliera Cardinale Giovanni Panico

🇮🇹

Lecce, Other, Italy

IRCCS Ospedale San Raffaele

🇮🇹

Milano, Other, Italy

Istituto Europeo di Oncologia

🇮🇹

Milano, Other, Italy

Azienda Ospedaliera Universitaria (AOU) Federico II

🇮🇹

Napoli, Other, Italy

AOOR Villa Sofia Cervello - Presidio V. Cervello

🇮🇹

Palermo, Other, Italy

Azienda Ospedaliero Universitaria di Parma

🇮🇹

Parma, Other, Italy

IRCSS Policlinico San Matteo

🇮🇹

Pavia, Other, Italy

Universita degli Studi di Perugia Azienda Ospedaliera di Perugia (Ospedale Santa Maria della Misericordia)

🇮🇹

Perugia, Other, Italy

UO Ematologia Ravenna

🇮🇹

Ravenna, Other, Italy

AUSL della Romagna Ospedale Infermi

🇮🇹

Rimini, Other, Italy

Policlinico Universitario Agostino Gemelli

🇮🇹

Roma, Other, Italy

IRCCS Ospedale Casa Sollievo della Sofferenza

🇮🇹

San Giovanni Rotondo (Foggia), Other, Italy

Azienda Sanitaria Universitaria Giuliano Isontina

🇮🇹

Trieste, Other, Italy

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

🇮🇹

Milano, Italy

Dong-A University Hospital

🇰🇷

Busan, Other, Korea, Republic of

Pusan National University Hospital

🇰🇷

Busan, Other, Korea, Republic of

Kosin University Gospel Hospital

🇰🇷

Busan, Other, Korea, Republic of

Inje University Busan-Paik Hospital

🇰🇷

Busan, Other, Korea, Republic of

Keimyung University Dongsan Medical Center

🇰🇷

Daegu, Other, Korea, Republic of

National Cancer Center

🇰🇷

Goyang-si, Other, Korea, Republic of

Gachon University Gil Medical Center

🇰🇷

Incheon, Other, Korea, Republic of

Jeonbuk National University Hospital

🇰🇷

Jeonju-Si, Other, Korea, Republic of

Severance Hospital, Yonsei University Health System

🇰🇷

Seoul, Other, Korea, Republic of

Soon Chun Hyang University Hospital Seoul

🇰🇷

Seoul, Other, Korea, Republic of

Asan Medical Center - Oncology

🇰🇷

Seoul, Other, Korea, Republic of

Samsung Medical Center

🇰🇷

Seoul, Other, Korea, Republic of

Ewha Womans University Mokdong Hospital

🇰🇷

Seoul, Other, Korea, Republic of

Seoul Saint Mary's Hospital

🇰🇷

Seoul, Other, Korea, Republic of

St. Vincent's Hospital, The Catholic University of Korea

🇰🇷

Suwon-si, Other, Korea, Republic of

Slingeland ziekenhuis

🇳🇱

Doetinchem, Other, Netherlands

Pratia Onkologia Katowice

🇵🇱

Katowice, Other, Poland

Pratia MCM Krakow

🇵🇱

Krakow, Other, Poland

Warmian-Masurian Cancer Center of The Ministry of The Interior and Administraton's Hospital

🇵🇱

Olsztyn, Other, Poland

Pratia Poznan

🇵🇱

Skorzewo, Other, Poland

Nasz Lekarz Osrodek Badan Klinicznych

🇵🇱

Torun, Other, Poland

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy

🇵🇱

Warsaw, Other, Poland

Hospital Universitari Germans Trias i Pujol

🇪🇸

Badalona, Other, Spain

Hospital del Mar

🇪🇸

Barcelona, Other, Spain

Hospital Universitari Vall d'Hebron

🇪🇸

Barcelona, Other, Spain

Hospital de la Santa Creu i Sant Pau

🇪🇸

Barcelona, Other, Spain

Hospital San Pedro de Alcantara

🇪🇸

Caceres, Other, Spain

Institut Catala d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)

🇪🇸

L'Hospitalet de Llobregat, Other, Spain

Clinica Universidad de Navarra

🇪🇸

Pamplona, Spain

Hospital Universitario Infanta Leonor

🇪🇸

Madrid, Other, Spain

Hospital Universitario Fundacion Jimenez Diaz

🇪🇸

Madrid, Other, Spain

Hospital Puerta de Hierro Majadahonda

🇪🇸

Madrid, Other, Spain

Hospital Universitario 12 de Octubre

🇪🇸

Madrid, Other, Spain

Hospital Universitario La Paz

🇪🇸

Madrid, Other, Spain

Hospital Regional Universitario de Malaga - Hospital General

🇪🇸

Malaga, Other, Spain

Hospital Costa del Sol

🇪🇸

Marbella, Other, Spain

Hospital Universitario Central de Asturias

🇪🇸

Oviedo, Other, Spain

Complejo Hospitalario de Navarra

🇪🇸

Pamplona, Other, Spain

Hospital Universitario Quironsalud Madrid

🇪🇸

Pozuelo de Alarcon, Other, Spain

Hospital Clínico Universitario de Salamanca

🇪🇸

Salamanca, Other, Spain

Universitatsspital Basel

🇨🇭

Basel, Other, Switzerland

Kantonsspital Winterthur (KSW)

🇨🇭

Winterthur, Other, Switzerland

Universitatsspital Zurich

🇨🇭

Zurich, Other, Switzerland

Chang Gung Memorial Hospital - Kaohsiung

🇨🇳

Kaohsiung, Other, Taiwan

China Medical University Hospital

🇨🇳

Taichung, Other, Taiwan

Chang Gung Memorial Hospital - Taoyuan

🇨🇳

Tainan, Other, Taiwan

National Cheng-Kung University Hospital

🇨🇳

Tainan, Other, Taiwan

Chi Mei Hospital Liouying

🇨🇳

Tainan, Other, Taiwan

National Taiwan University Hospital

🇨🇳

Taipei, Other, Taiwan

Taipei Veterans General Hospital

🇨🇳

Taipei, Other, Taiwan

East Sussex Healthcare NHS Trust

🇬🇧

Eastbourne, Other, United Kingdom

University Hospitals Birmingham NHS Foundation Trust

🇬🇧

Edgbaston, Birmingham, Other, United Kingdom

St Bartholomew's Hospital

🇬🇧

London, Other, United Kingdom

Guy's and St Thomas' NHS Foundation

🇬🇧

London, Other, United Kingdom

The Royal Marsden Hospital

🇬🇧

London, Other, United Kingdom

Maidstone and Tunbridge Wells NHS Trust

🇬🇧

Maidstone, Other, United Kingdom

The Royal Marsden Hospital (Surrey)

🇬🇧

Sutton, Other, United Kingdom

Singleton Hospital

🇬🇧

Swansea, Other, United Kingdom

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