Clinical trial NCT04404283: Brentuximab Vedotin Plus Lenalidomide and Rituximab for the Treatment of Relapsed/Refractory DLBCL
Official title: A Randomized, Double-blind, Placebo-Controlled, Active-Comparator, Multicenter, Phase 3 Study of Brentuximab Vedotin or Placebo in Combination With Lenalidomide and Rituximab in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Diffuse Large B-cell Lymphoma
Keywords: Seattle Genetics
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
First posted: 2020-05-27
Enrollment: 241
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Overall survival (OS)
timeFrame: Approximately 2 years
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Approximately 1 year
measure: Objective response rate (ORR)
timeFrame: Approximately 1 year
measure: Complete response (CR) rate
timeFrame: Approximately 1 year
measure: Duration of response (DOR)
timeFrame: Approximately 1 year
measure: Incidence of adverse events
timeFrame: Approximately 1 year
measure: OS in CD30+ participants
timeFrame: Approximately 2 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Central Alabama Research
state: Alabama
city: Birmingham
country: United States
facility: Alabama Oncology
state: Alabama
city: Goodyear
country: United States
facility: Arizona Oncology Associates, PC - NAHOA
state: Arizona
city: Riverside
country: United States
facility: The Oncology Institute of Hope & Innovation - California
state: California
city: Sacramento
country: United States
facility: University of California Davis
state: California
city: Torrance
country: United States
facility: Lundquist Institute/Harbor-UCLA
state: California
city: Fort Myers
country: United States
facility: Florida Cancer Specialists - South Region
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists - North Region
state: Florida
city: West Palm Beach
country: United States
facility: Florida Cancer Specialists - East West Palm Beach, FL (SCRI)
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Niles
country: United States
facility: Illinois Cancer Specialists
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Detroit
country: United States
facility: Karmanos Cancer Institute / Wayne State University
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Grand Rapids
country: United States
facility: Cancer and Hematology Centers of Western Michigan / Lemmen-Holton Cancer Pavilion
state: Michigan
city: Grosse Pointe Woods
country: United States
facility: Ascension St John Hospital
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Kansas City
country: United States
facility: HCA Midwest Health Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Saint Louis
country: United States
facility: Washington University in St Louis
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Camden
country: United States
facility: MD Anderson Cancer Center at Cooper Health
state: New Jersey
city: Florham Park
country: United States
facility: Summit Medical Group
state: New Jersey
city: Shirley
country: United States
facility: New York Cancer and Blood Specialists
state: New York
city: Cincinnati
country: United States
facility: Oncology Hematology Care
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Cancer Institute
state: Ohio
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute and Research Center
state: Oregon
city: Charleston
country: United States
facility: Roper St. Francis Healthcare
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina/Hollings Cancer Center
state: South Carolina
city: Greenville
country: United States
facility: Saint Francis Hospital / Bon Secours - South Carolina
state: South Carolina
city: Greenville
country: United States
facility: Prisma Health
state: South Carolina
city: Knoxville
country: United States
facility: University of Tennessee
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology - Austin Midtown
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology - San Antonio Medical Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Vancouver
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Washington
city: Madison
country: United States
facility: Carbone Cancer Center / University of Wisconsin
state: Wisconsin
city: Wauwatosa
country: United States
facility: Aurora Health Care, Inc
state: Wisconsin
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: Other
city: Gosford
country: Australia
facility: Central Coast Local Health District (Gosford and Wyong Hospitals)
state: Other
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Other
city: Nedlands
country: Australia
facility: Hollywood Haematology
state: Other
city: Saint Leonards
country: Australia
facility: Royal North Shore Hospital
state: Other
city: Antwerpen
country: Belgium
facility: Ziekenhuis Netwerk Antwerpen Campus Stuivenberg
state: Other
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
state: Other
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
state: Other
city: Haine-Saint-Paul
country: Belgium
facility: CHU Helora Hopital de La Louviere Site Jolimont
state: Other
city: Ottignies
country: Belgium
facility: Clinique Saint Pierre
state: Other
city: Roeselare
country: Belgium
facility: AZ Delta - Campus Wilgenstraat
state: Other
city: Yvoir
country: Belgium
facility: CHU UCL Namur
state: Other
city: St John's
country: Canada
facility: H. Bliss Murphy Cancer Centre / Eastern Regional Health Authority
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre
state: Nova Scotia
city: East Brampton
country: Canada
facility: William Osler Health Sciences
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre - Victoria Hospital
state: Ontario
city: Oshawa
country: Canada
facility: Lakeridge Health - The R.S. McLaughlin Durham Regional Cancer Centre (MDRCC)
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa / Ottawa General Hospital
state: Ontario
city: Greenfield Park
country: Canada
facility: CISSS de la Monteregie-Centre
state: Quebec
city: Montreal
country: Canada
facility: CIUSSS de L'Est de l'lle de Montreal / installation Hopital Maisonneuve-Rosemont
state: Quebec
city: Montreal
country: Canada
facility: CIUSS NIM/Hopital du Sacre-Coeur de Montreal
state: Quebec
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove-oddeleni klinicke hematologie
state: Other
city: Praha 10
country: Czechia
facility: Fakultni Nemocnice Kralovske Vinohrady
state: Other
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
state: Other
city: Aalborg
country: Denmark
facility: Aalborg Universitetshospital
state: Other
city: Aarhus N
country: Denmark
facility: Aarhus University Hospital
state: Other
city: Copenhagen
country: Denmark
facility: Rigshospitalet
state: Other
city: Roskilde
country: Denmark
facility: Zealand University Hospital (Roskilde Sygehus)
state: Other
city: Angers Cedex 9
country: France
facility: Center Hospitalier Universitaire d' Angers
state: Other
city: Bordeaux
country: France
facility: Centre de Lutte Contre le Cancer (CLCC) - Institut Bergonie
state: Other
city: Brest Cedex
country: France
facility: Centre Hospitalier Regional Universitaire (CHRU) Brest - Hopital Morvan
state: Other
city: Cedex 9
country: France
facility: CHD Vendee, Site de La Roche-sur-Yon, Les Oudairies
state: Other
city: Chambery
country: France
facility: Centre Hospitalier Metropole Savoie - Chambery
state: Other
city: Corbeil-Essonnes
country: France
facility: Centre Hospitalier Sud Francilien
state: Other
city: Dijon
country: France
facility: Centre Hospitalier Universitaire (CHU) Dijon Bourgogne
state: Other
city: Grenoble
country: France
facility: Centre Hospitalier Universitaire de Grenoble
state: Other
city: Le Mans
country: France
facility: Centre Hospitalier Le Mans
state: Other
city: Limoges Cedex
country: France
facility: Centre Hospitalier Universitaire (CHU) De Limoges - Hopital Dupuytren
state: Other
city: Lyon
country: France
facility: Centre Leon Berard - Centre regional de lutte contre le cancer Rhone-Alpes
state: Other
city: Metz
country: France
facility: Centre Hospitalier Regional Metz-Thionville, Hopital Mercy
state: Other
city: Mulhouse
country: France
facility: Hopital Emile Muller
state: Other
city: Nantes cedex 1
country: France
facility: Centre Hospitalier Universitaire Nantes-Hotel Dieu
state: Other
city: Nice Cedex 2
country: France
facility: Centre de Lutte contre le Cancer (CLCC) - Centre Antoine Lacassagne
state: Other
city: Perpignan CEDEX
country: France
facility: Centre Hospitalier de Perpignan
state: Other
city: Pessac Cedex
country: France
facility: CHU Bordeaux Hopital Haut-Leveque
state: Other
city: Pierre-Benite Cedex
country: France
facility: Centre Hospitalier Lyon Sud
state: Other
city: Rouen
country: France
facility: Centre Henri Becquerel / Centre Regional de Lutte Contre le Cancer
state: Other
city: Saint Etienne Cedex 2
country: France
facility: Institut de Cancerologie Hematologie Universitaire de Saint Etienne (I.CHU.SE)
state: Other
city: Vandoeuvre-Les-Nancy Cedex 9
country: France
facility: Centre Hospitalier Universitaire de Nancy - Hopital de Brabois
state: Other
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy
state: Other
city: Paris
country: France
facility: CHU Tours - Hopital Bretonneau
city: Paris
country: France
facility: Hopital Saint-Antoine
city: Bonn
country: Germany
facility: Medizinische Klinik & Poliklinik III (Bonn)nUniversitätsklinikum Bonn
state: Other
city: Brandenburg
country: Germany
facility: Stadtisches Klinikum Brandenburg GmbH
state: Other
city: Duesseldorf
country: Germany
facility: Universitaetsklinikum Dusseldorf
state: Other
city: Halle (S.)
country: Germany
facility: Universitaetsklinikum Halle (Saale)
state: Other
city: Aviano (Pordenone)
country: Italy
facility: Centro di Riferimento Oncologico di Aviano
state: Other
city: Bari
country: Italy
facility: IRCCS Istituto Tumori Giovanni Paolo II
state: Other
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi
state: Other
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi
state: Other
city: Genova
country: Italy
facility: Azienda Ospedaliera Universitaria San Martino
state: Other
city: Lecce
country: Italy
facility: Azienda Ospedaliera Cardinale Giovanni Panico
state: Other
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
state: Other
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
state: Other
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria (AOU) Federico II
state: Other
city: Palermo
country: Italy
facility: AOOR Villa Sofia Cervello - Presidio V. Cervello
state: Other
city: Parma
country: Italy
facility: Azienda Ospedaliero Universitaria di Parma
state: Other
city: Pavia
country: Italy
facility: IRCSS Policlinico San Matteo
state: Other
city: Perugia
country: Italy
facility: Universita degli Studi di Perugia Azienda Ospedaliera di Perugia (Ospedale Santa Maria della Misericordia)
state: Other
city: Ravenna
country: Italy
facility: UO Ematologia Ravenna
state: Other
city: Rimini
country: Italy
facility: AUSL della Romagna Ospedale Infermi
state: Other
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
state: Other
city: San Giovanni Rotondo (Foggia)
country: Italy
facility: IRCCS Ospedale Casa Sollievo della Sofferenza
state: Other
city: Trieste
country: Italy
facility: Azienda Sanitaria Universitaria Giuliano Isontina
state: Other
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
state: Other
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
state: Other
city: Busan
country: Korea, Republic of
facility: Kosin University Gospel Hospital
state: Other
city: Busan
country: Korea, Republic of
facility: Inje University Busan-Paik Hospital
state: Other
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
state: Other
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Other
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
state: Other
city: Jeonju-Si
country: Korea, Republic of
facility: Jeonbuk National University Hospital
state: Other
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
state: Other
city: Seoul
country: Korea, Republic of
facility: Soon Chun Hyang University Hospital Seoul
state: Other
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center - Oncology
state: Other
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Other
city: Seoul
country: Korea, Republic of
facility: Ewha Womans University Mokdong Hospital
state: Other
city: Seoul
country: Korea, Republic of
facility: Seoul Saint Mary's Hospital
state: Other
city: Suwon-si
country: Korea, Republic of
facility: St. Vincent's Hospital, The Catholic University of Korea
state: Other
city: Doetinchem
country: Netherlands
facility: Slingeland ziekenhuis
state: Other
city: Katowice
country: Poland
facility: Pratia Onkologia Katowice
state: Other
city: Krakow
country: Poland
facility: Pratia MCM Krakow
state: Other
city: Olsztyn
country: Poland
facility: Warmian-Masurian Cancer Center of The Ministry of The Interior and Administraton's Hospital
state: Other
city: Skorzewo
country: Poland
facility: Pratia Poznan
state: Other
city: Torun
country: Poland
facility: Nasz Lekarz Osrodek Badan Klinicznych
state: Other
city: Warsaw
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy
state: Other
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: Other
city: Barcelona
country: Spain
facility: Hospital del Mar
state: Other
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Other
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
state: Other
city: Caceres
country: Spain
facility: Hospital San Pedro de Alcantara
state: Other
city: L'Hospitalet de Llobregat
country: Spain
facility: Institut Catala d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
state: Other
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra
state: Other
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor
state: Other
city: Madrid
country: Spain
facility: Hospital Puerta de Hierro Majadahonda
state: Other
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
state: Other
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
state: Other
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
state: Other
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga - Hospital General
state: Other
city: Marbella
country: Spain
facility: Hospital Costa del Sol
state: Other
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Other
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
state: Other
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Universitario Quironsalud Madrid
state: Other
city: Salamanca
country: Spain
facility: Hospital Clínico Universitario de Salamanca
state: Other
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Basel
country: Switzerland
facility: Universitatsspital Basel
state: Other
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur (KSW)
state: Other
city: Zurich
country: Switzerland
facility: Universitatsspital Zurich
state: Other
city: Kaohsiung
country: Taiwan
facility: Chang Gung Memorial Hospital - Kaohsiung
state: Other
city: Taichung
country: Taiwan
facility: China Medical University Hospital
state: Other
city: Tainan
country: Taiwan
facility: Chang Gung Memorial Hospital - Taoyuan
state: Other
city: Tainan
country: Taiwan
facility: National Cheng-Kung University Hospital
state: Other
city: Tainan
country: Taiwan
facility: Chi Mei Hospital Liouying
state: Other
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
state: Other
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
state: Other
city: Eastbourne
country: United Kingdom
facility: East Sussex Healthcare NHS Trust
state: Other
city: Edgbaston, Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
state: Other
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
state: Other
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation
state: Other
city: London
country: United Kingdom
facility: The Royal Marsden Hospital
state: Other
city: Maidstone
country: United Kingdom
facility: Maidstone and Tunbridge Wells NHS Trust
state: Other
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital (Surrey)
state: Other
city: Swansea
country: United Kingdom
facility: Singleton Hospital
state: Other
Study officials:
affiliation: Pfizer
name: Pfizer Ct.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Ward JP, Berrien-Elliott MM, Gomez F, Luo J, Becker-Hapak M, Cashen AF, Wagner-Johnston ND, Maddocks K, Mosior M, Foster M, Krysiak K, Schmidt A, Skidmore ZL, Desai S, Watkins MP, Fischer A, Griffith M, Griffith OL, Fehniger TA, Bartlett NL. Phase 1/dose expansion trial of brentuximab vedotin and lenalidomide in relapsed or refractory diffuse large B-cell lymphoma. Blood. 2022 Mar 31;139(13):1999-2010. doi: 10.1182/blood.2021011894.