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

Diffuse Large B-cell Lymphoma Clinical Trial

— ECHELON-3  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04404283
• Other study ID #: SGN35-031
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 20, 2020
• Est. completion date: April 30, 2027

Study information

• Verified date: June 2024
• Source: Seagen Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 240
• Est. completion date: April 30, 2027
• Est. primary completion date: May 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diffuse Large B-cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Brentuximab vedotin
1.2 mg/kg administered into the vein (IV; intravenously) infusion every 3 weeks
• Rituximab
375 mg/m^2 administered via intravenous infusion on Cycle 1 Day 1. 1400 mg injected under the skin (subcutaneous) permitted every 3 weeks from Cycle 2 Day 1 through end of treatment.
• Lenalidomide
20 mg given by mouth (orally) daily

Other:
• Placebo
Administered via intravenous infusion every 3 weeks

Locations

Country	Name	City	State
Australia	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
Belgium	Ziekenhuis Netwerk Antwerpen Campus Stuivenberg	Antwerpen	Other
Belgium	Universitair Ziekenhuis Antwerpen	Edegem	Other
Belgium	Universitair Ziekenhuis Gent	Gent	Other
Belgium	Hopital de Jolimont	Haine-Saint-Paul	Other
Belgium	Clinique Saint Pierre	Ottignies	Other
Belgium	AZ Delta - Campus Wilgenstraat	Roeselare	Other
Belgium	CHU UCL Namur	Yvoir	Other
Canada	William Osler Health Sciences	East Brampton	Ontario
Canada	CISSS de la Monteregie-Centre	Greenfield Park	Quebec
Canada	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia
Canada	London Health Sciences Centre - Victoria Hospital	London	Ontario
Canada	CIUSS NIM/Hopital du Sacre-Coeur de Montreal	Montreal	Quebec
Canada	CIUSSS de L'Est de l'lle de Montreal / installation Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	Lakeridge Health - The R.S. McLaughlin Durham Regional Cancer Centre (MDRCC)	Oshawa	Ontario
Canada	University of Ottawa / Ottawa General Hospital	Ottawa	Ontario
Canada	H. Bliss Murphy Cancer Centre / Eastern Regional Health Authority	St John's	Newfoundland and Labrador
Czechia	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
Denmark	Aalborg Universitetshospital	Aalborg	Other
Denmark	Aarhus University Hospital	Aarhus N	Other
Denmark	Rigshospitalet	Copenhagen	Other
Denmark	Zealand University Hospital (Roskilde Sygehus)	Roskilde	Other
France	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	CHU Tours - Hopital Bretonneau	Paris
France	Hopital Saint-Antoine	Paris
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
Germany	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
Italy	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	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano
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
Korea, Republic of	Dong-A University Hospital	Busan	Other
Korea, Republic of	Inje University Busan-Paik Hospital	Busan	Other
Korea, Republic of	Kosin University Gospel Hospital	Busan	Other
Korea, Republic of	Pusan National University 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	Asan Medical Center - Oncology	Seoul	Other
Korea, Republic of	Ewha Womans University Mokdong Hospital	Seoul	Other
Korea, Republic of	Samsung Medical Center	Seoul	Other
Korea, Republic of	Seoul Saint Mary's Hospital	Seoul	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	St. Vincent's Hospital, The Catholic University of Korea	Suwon-si	Other
Netherlands	Slingeland ziekenhuis	Doetinchem	Other
Poland	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
Spain	Hospital Universitari Germans Trias i Pujol	Badalona	Other
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona	Other
Spain	Hospital del Mar	Barcelona	Other
Spain	Hospital Universitari Vall d'Hebron	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	Madrid	Other
Spain	Hospital Puerta de Hierro Majadahonda	Madrid	Other
Spain	Hospital Universitario 12 de Octubre	Madrid	Other
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid	Other
Spain	Hospital Universitario Infanta Leonor	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	Clinica Universidad de Navarra	Pamplona	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
Switzerland	Universitatsspital Basel	Basel	Other
Switzerland	Kantonsspital Winterthur (KSW)	Winterthur	Other
Switzerland	Universitatsspital Zurich	Zurich	Other
Taiwan	Chang Gung Memorial Hospital - Kaohsiung	Kaohsiung	Other
Taiwan	China Medical University Hospital	Taichung	Other
Taiwan	Chang Gung Memorial Hospital - Taoyuan	Tainan	Other
Taiwan	Chi Mei Hospital Liouying	Tainan	Other
Taiwan	National Cheng-Kung University Hospital	Tainan	Other
Taiwan	National Taiwan University Hospital	Taipei	Other
Taiwan	Taipei Veterans General Hospital	Taipei	Other
United Kingdom	East Sussex Healthcare NHS Trust	Eastbourne	Other
United Kingdom	University Hospitals Birmingham NHS Foundation Trust	Edgbaston, Birmingham	Other
United Kingdom	Guy's and St Thomas' NHS Foundation	London	Other
United Kingdom	St Bartholomew's Hospital	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 States	Texas Oncology - Austin Midtown	Austin	Texas
United States	University of Maryland	Baltimore	Maryland
United States	Alabama Oncology	Birmingham	Alabama
United States	Central Alabama Research	Birmingham	Alabama
United States	MD Anderson Cancer Center at Cooper Health	Camden	New Jersey
United States	Medical University of South Carolina/Hollings Cancer Center	Charleston	South Carolina
United States	Roper St. Francis Healthcare	Charleston	South Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Rush University Medical Center	Chicago	Illinois
United States	Oncology Hematology Care	Cincinnati	Ohio
United States	University of Cincinnati Cancer Institute	Cincinnati	Ohio
United States	Henry Ford Health System	Detroit	Michigan
United States	Karmanos Cancer Institute / Wayne State University	Detroit	Michigan
United States	Willamette Valley Cancer Institute and Research Center	Eugene	Oregon
United States	Summit Medical Group	Florham Park	New Jersey
United States	Florida Cancer Specialists - South Region	Fort Myers	Florida
United States	Arizona Oncology Associates, PC - NAHOA	Goodyear	Arizona
United States	Cancer and Hematology Centers of Western Michigan / Lemmen-Holton Cancer Pavilion	Grand Rapids	Michigan
United States	Prisma Health	Greenville	South Carolina
United States	Saint Francis Hospital / Bon Secours - South Carolina	Greenville	South Carolina
United States	Ascension St John Hospital	Grosse Pointe Woods	Michigan
United States	HCA Midwest Health Kansas City	Kansas City	Missouri
United States	University of Tennessee	Knoxville	Tennessee
United States	Carbone Cancer Center / University of Wisconsin	Madison	Wisconsin
United States	Illinois Cancer Specialists	Niles	Illinois
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	New York Cancer and Blood Specialists	Port Jefferson Station	New York
United States	The Oncology Institute of Hope & Innovation - California	Riverside	California
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	University of California Davis	Sacramento	California
United States	Saint Louis University	Saint Louis	Missouri
United States	Washington University in St Louis	Saint Louis	Missouri
United States	Florida Cancer Specialists - North Region	Saint Petersburg	Florida
United States	Texas Oncology - San Antonio Medical Center	San Antonio	Texas
United States	Lundquist Institute/Harbor-UCLA	Torrance	California
United States	Northwest Cancer Specialists, P.C.	Vancouver	Washington
United States	Aurora Health Care, Inc	Wauwatosa	Wisconsin
United States	Florida Cancer Specialists - East West Palm Beach, FL (SCRI)	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Seagen Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Czechia,  Denmark,  France,  Germany,  Italy,  Korea, Republic of,  Netherlands,  Poland,  Spain,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival (OS)	OS is defined as the time from the date of randomization to date of death due to any cause	Approximately 2 years
Secondary	Progression-free survival (PFS)	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)	Approximately 1 year
Secondary	Objective response rate (ORR)	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).	Approximately 1 year
Secondary	Complete response (CR) rate	Proportion of participants with best response of CR according to investigator assessment per the Lugano Criteria for Response Assessment (Cheson 2014)	Approximately 1 year
Secondary	Duration of response (DOR)	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.	Approximately 1 year
Secondary	Incidence of adverse events	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.	Approximately 1 year
Secondary	OS in CD30+ participants	Time from the date of randomization to date of death due to any cause.	Approximately 2 years