Clinical trial NCT04002297: A Study to Investigate the Efficacy of Zanubrutinib Plus Rituximab Compared With Bendamustine Plus Rituximab in Adults With Previously Untreated Mantle Cell Lymphoma Who Are Ineligible for Stem Cell Transplantation
Official title: A Phase 3 Randomized, Open-Label, Multicenter Study Comparing Zanubrutinib (BGB-3111) Plus Rituximab Versus Bendamustine Plus Rituximab in Patients With Previously Untreated Mantle Cell Lymphoma Who Are Ineligible for Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Mantle Cell Lymphoma; Non-Hodgkin Lymphoma
Keywords: MCL, NHL, BTKi
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2019-06-28
Enrollment: 510
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized study to compare the efficacy and safety of zanubrutinib plus rituximab versus bendamustine plus rituximab in previously untreated participants with mantle cell lymphoma (MCL) who are not eligible for stem cell transplantation.


Eligibility criteria: Key Inclusion Criteria:

1. ≥70 years of age at the time of informed consent, OR ≥60 and \<70 years of age with comorbidities precluding autologous stem cell transplantation
2. Histologically confirmed diagnosis of MCL
3. No prior systemic treatments for MCL
4. Measurable disease by CT/MRI
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
6. Adequate marrow and organ function

Key Exclusion Criteria:

1. Known central nervous system involvement by lymphoma
2. Participants for whom the goal of therapy is tumor debulking prior to stem cell transplant
3. Clinically significant cardiovascular disease
4. History of severe bleeding disorder
5. Unable to swallow capsules or disease significantly affecting gastrointestinal function
6. Active fungal, bacterial and/or viral infection requiring systemic therapy
7. Requires ongoing treatment with a strong CYP3A inhibitor or inducer

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Progression-free survival (PFS) determined by independent central review
timeFrame: Up to approximately 7 years
Secondary outcomes:
measure: PFS by investigator assessment
timeFrame: Up to approximately 7 years
measure: Overall response rate (ORR)
timeFrame: Up to approximately 7 years
measure: Duration of response (DOR)
timeFrame: Up to approximately 7 years
measure: Overall survival (OS)
timeFrame: Up to approximately 7 years
measure: Time to Response (TTR)
timeFrame: Up to approximately 7 years
measure: Rate of complete response (CR) or complete metabolic response
timeFrame: Up to approximately 7 years
measure: Participant-reported outcomes (PROs) as assessed by the European Quality of Life 5-Dimension 5 Level Questionnaire (EQ-5D-5L)
timeFrame: Up to approximately 7 years
measure: PROs as assessed by the European Organization for Research on Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
timeFrame: Up to approximately 7 years
measure: Number of participants with adverse events and serious adverse events
timeFrame: Up to approximately 7 years
Other outcomes:
Locations:
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center
state: California
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center (Bidmc)
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: New York
country: United States
facility: Icahn School of Medicine At Mount Sinai
state: New York
city: Westbury
country: United States
facility: Clinical Research Alliance, Inc
state: New York
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Pittsburgh
country: United States
facility: West Penn Hospital
state: Pennsylvania
city: Houston
country: United States
facility: The University of Texas Md Anderson Cancer Center
state: Texas
city: Lubbock
country: United States
facility: Joe Arrington Cancer Research and Treatment Center
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Garran
country: Australia
facility: Canberra Hospital
state: Australian Capital Territory
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Cudgen
country: Australia
facility: The Tweed Valley Hospital
state: New South Wales
city: Darlinghurst
country: Australia
facility: Saint Vincents Hospital Sydney
state: New South Wales
city: Gosford
country: Australia
facility: Gosford Hospital
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Birtinya
country: Australia
facility: Sunshine Coast Hospital and Health Service
state: Queensland
city: South Brisbane
country: Australia
facility: Icon Cancer Foundation
state: Queensland
city: Bedford PK
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Fitzroy
country: Australia
facility: St Vincents Hospital Melbourne
state: Victoria
city: Frankston
country: Australia
facility: Peninsula Private Hospital
state: Victoria
city: Geelong
country: Australia
facility: Barwon Health the Geelong Hospital
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Linz
country: Austria
facility: Ordensklinikum Linz Gmbh Elisabethinen
city: Salzburg
country: Austria
facility: Universitatsklinik Fur Innere Medizin Iii Universitatsklinikum Der Pmu Landeskrankenhaus Salzburg
city: Vienna
country: Austria
facility: Medical University Vienna Oncology
city: Brugge
country: Belgium
facility: Az Sint Jan Brugge
city: Brussels
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Edegem
country: Belgium
facility: Uz Antwerpen
city: Kortrijk
country: Belgium
facility: Az Groeninge Campus Loofstraat
city: Liege
country: Belgium
facility: Centre Hospitalier Universitaire (Chu) de Liege Site Du Sart Tilman
city: Yvoir
country: Belgium
facility: Centre Hospitalier Universitaire Universite Catholique de Louvain Site Godinne
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Sherbrooke
country: Canada
facility: Ciusss de Lestrie Chus
state: Quebec
city: Beijing
country: China
facility: Peking University Peoples Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Quanzhou
country: China
facility: Quanzhou First Affliated Hospital of Fujian Medical University
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat Sen University Cancer Center
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Provincial Peoples Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guangdong
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University Branch Donghu
state: Jiangxi
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Shanghai
country: China
facility: Shanghai East Hospital
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Institute of Hematology and Hospital of Blood Disease
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Urumqi
country: China
facility: Affiliated Cancer Hospital of Xinjiang Medical University
state: Xinjiang
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Ningbo
country: China
facility: Hwa Mei Hospital, University of Chinese Academy of Sciences (Ningbo No Hospital)
state: Zhejiang
city: Bordeaux
country: France
facility: Centre de Lutte Contre Le Cancer Institut Bergonie
city: Brest
country: France
facility: Chru de Brest Hospital Morvan
city: Dijon
country: France
facility: Chu Dijon
city: Grenoble Cedex
country: France
facility: Chu Grenoble Alpes
city: Le Mans
country: France
facility: Centre Hospitalier Le Mans
city: Lille
country: France
facility: Hopital Claude Huriez Chu Lille
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Nantes Cedex
country: France
facility: Centre Hospitalier Universitaire Nantes Hotel Dieu
city: Paris
country: France
facility: Institut Curie
city: Paris
country: France
facility: Necker University Hospital
city: PierreBenite
country: France
facility: Chu Hopital Lyon Sud
city: Poitiers
country: France
facility: Centre Hospitalier Universitaire de Poitier Hopital de La Miletrie Hopital Jean Bernard
city: Quimper
country: France
facility: Ch Cornouaille
city: Toulouse
country: France
facility: Iuc Toulouse Oncopole
city: Heidelberg
country: Germany
facility: Universitatsklinikum Heidelberg
city: Koln
country: Germany
facility: Uniklinik Koln (Aor)
city: Munich
country: Germany
facility: Dept of Medicine Iii, University Hospitallmu
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm, Innere Medizin Iii
city: Wuppertal
country: Germany
facility: Petrus Krankenhaus Wuppertal
city: Cork
country: Ireland
facility: Cork University Hospital
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital
city: Dublin
country: Ireland
facility: St Jamess Hospital
city: Galway
country: Ireland
facility: University Hospital Galway
city: Limerick
country: Ireland
facility: University Hospital Limerick
city: Waterford
country: Ireland
facility: University Hospital Waterford
city: Alessandria
country: Italy
facility: Azienda Ospedaliera Nazionale Ssantonio E Biagio E Cesare Arrigo
city: Bologna
country: Italy
facility: Policlinico Sorsola Malpighi, Aou Di Bologna
city: Genova
country: Italy
facility: Azienda Ospedaliera Universitaria San Martino
city: Milano
country: Italy
facility: Niguarda Cancer Center Division of Hematology
city: Novara
country: Italy
facility: Aou Maggiore Della Carita
city: Palermo
country: Italy
facility: Aoor Villa Sofia Cervello
city: Pisa
country: Italy
facility: Aou Pisana, Stabilimento Di Santa Chiara
city: Ravenna
country: Italy
facility: Unita Di Ematologia, Dipartimento Di Ematologia Ed Oncologia
city: Reggio Emilia
country: Italy
facility: Azienda Unita Sanitaria Locale Irccs
city: Roma
country: Italy
facility: Universita Degli Studi La Sapienza
city: Siena
country: Italy
facility: Aou Senese Policlinico Santa Maria Alle Scotte
city: Torino
country: Italy
facility: Ao Citta Della Salute E Della Scienza Di Torino Presidio O
city: Verona
country: Italy
facility: University of Verona
city: Nagoyashi
country: Japan
facility: National Hospital Organization Nagoya Medical Center
state: Aichi
city: Toyohashi
country: Japan
facility: Toyohashi Municipal Hospital
state: Aichi
city: Chibashi
country: Japan
facility: Chiba Cancer Center
state: Chiba
city: Kurume
country: Japan
facility: Kurume University Hospital
state: Fukuoka
city: Hiroshimashi
country: Japan
facility: Hiroshima Red Cross Hospital and Atomic Bomb Survivors Hospital
state: Hiroshima
city: Yokohamashi
country: Japan
facility: Kanagawa Cancer Center
state: Kanagawa
city: Kumamotoshi
country: Japan
facility: National Hospital Organization Kumamoto Medical Center
state: Kumamoto
city: Sendaishi
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Kurashikishi
country: Japan
facility: Kurashiki Central Hospital
state: Okayama
city: Osakashi
country: Japan
facility: Osaka Red Cross Hospital
state: Osaka
city: Chuoku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Kyoto
country: Japan
facility: University Hospital, Kyoto Prefectural Univ of Medicine
city: Okayama
country: Japan
facility: National Hospital Organization Okayama Medical Center
city: Osaka
country: Japan
facility: Osaka Metropolitan University Hospital
city: Tokyo
country: Japan
facility: Tokyo Medical and Dental University Hospital
city: Yokohamashi
country: Japan
facility: Yokohama Municipal Citizens Hospital
city: Den Haag
country: Netherlands
facility: Hagaziekenhuis
city: Goes
country: Netherlands
facility: Admiraal de Ruijter Ziekenhuis
city: Groningen
country: Netherlands
facility: University of Medical Center Groningen (Umcg)
city: Nieuwegein
country: Netherlands
facility: St Antonius Ziekenhuis, Randd Interne Geneeskunde (F)
city: Nijmegen
country: Netherlands
facility: Albert Schweitzer Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus Mc
city: Christchurch
country: New Zealand
facility: Christchurch Hospital (Canterbury Health Laboratories)
city: Tauranga
country: New Zealand
facility: Tauranga Hospital
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki Nr Im Dr Jana Biziela
city: Chorzow
country: Poland
facility: Silesian Healthy Blood Clinic
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Gdask
country: Poland
facility: Copernicus Podmiot Leczniczy Sp Z Oo Wojewodzkie Centrum Onkologii
city: Gdynia
country: Poland
facility: Szpitale Pomorskie Spolka Z Ograniczona Odpowiedzialnoscia
city: Krakow
country: Poland
facility: Pratia McM Krakow
city: Legnica
country: Poland
facility: Wojewodzki Szpital Specjalistyczny W Legnicy
city: Lodz
country: Poland
facility: Wielospecjalistyczne Centrum Onkologii I Traumatologii Im M Kopernika W Lodzi
city: Lublin
country: Poland
facility: Centrum Onkologii Ziemi Lubelskiej
city: Walbrzych
country: Poland
facility: Specjalistyczny Szpital Im Dr Alfreda Sokolowskiego
city: Warszawa
country: Poland
facility: Instytut Hematologii I Transfuzjologii W Warszawie
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny Im Jana Mikulicza Radeckiego We Wroclawiu
city: Lisboa
country: Portugal
facility: Chuln Hospital de Santa Maria
city: Lisbon
country: Portugal
facility: Instituto Portugues Oncologia de Lisboa Francisco Gentil, Epe
city: Porto
country: Portugal
facility: Centro Hospitalar Universitario Porto
city: Porto
country: Portugal
facility: Instituto Portugues de Oncologia Do Porto Francisco Gentil, Epe
city: Bucuresti
country: Romania
facility: Institutul Clinic Fundeni
city: Iasi
country: Romania
facility: Institutul Regional de Oncologie Iasi
city: Moscow
country: Russian Federation
facility: Clinical Hospital, Sp Botkin
state: Moskva
city: Saint Petersburg
country: Russian Federation
facility: Fgu Russian Scientific Research Institute of Hematology and Transfusiology
state: Sankt-Peterburg
city: Saint Petersburg
country: Russian Federation
facility: Leningrad Regional Clinic and Hospital
state: Sankt-Peterburg
city: Moscow
country: Russian Federation
facility: Gbuz Mmcc Kommunarka Dzm
city: Barcelona
country: Spain
facility: Hospital Universitario Vall Dhebron
city: Barcelona
country: Spain
facility: Institut Catala Doncologia
city: Barcelona
country: Spain
facility: Ico Hug Trias I Pujol
city: Girona
country: Spain
facility: Ico Girona
city: Madrid
country: Spain
facility: Hospital Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Md Anderson Cancer Center Madrid Spain
city: Madrid
country: Spain
facility: Start Madrid Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Tainan
country: Taiwan
facility: Chi Mei Hospital Liouying
city: Taipei
country: Taiwan
facility: Tri Service General Hospital
city: Ankara
country: Turkey
facility: Dr Abdurrahman Yurtaslan Oncology Teaching and Research Hospital
city: Ankara
country: Turkey
facility: Hematoloji Ve Hematolik Onkoloji Tani Ve Tedavi Merezi
city: Ankara
country: Turkey
facility: Gazi University
city: Edirne
country: Turkey
facility: Tr Trakya University Health Research and Application Center (Hospital)
city: Istanbul
country: Turkey
facility: Vkv American Hospital
city: Mersin
country: Turkey
facility: Mersin Universitesi Tip Fakultesi Hastanesi
city: Cherkasy
country: Ukraine
facility: Cherkasy Regional Oncology Dispensary
city: Dnipro
country: Ukraine
facility: Municipal Non Profit Enterprise City Clinical Hospital
city: Kiev
country: Ukraine
facility: National Cancer Institute
city: Lviv
country: Ukraine
facility: Si Institute of Blood Pathology and Transfusion Medicine Nams of Ukraine, Hematology Department
city: Abergavenny
country: United Kingdom
facility: Aneurin Bevan University Health Board
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Dudley
country: United Kingdom
facility: Russells Hall Hopsital
city: Sutton
country: United Kingdom
facility: Royal Marsden Nhs Foundation Royal Marsden Hospital
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Dreyling M, Tam CS, Wang M, Smith SD, Ladetto M, Huang H, Novotny W, Co M, Romano A, Holmgren E, Huang J, Gouill SL. A Phase III study of zanubrutinib plus rituximab versus bendamustine plus rituximab in transplant-ineligible, untreated mantle cell lymphoma. Future Oncol. 2021 Jan;17(3):255-262. doi: 10.2217/fon-2020-0794. Epub 2020 Sep 28.