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

Phase 3

Active, not recruiting

• Conditions: Mantle Cell Lymphoma; Non-Hodgkin Lymphoma
• Interventions: Drug: zanubrutinib; Drug: bendamustine; Drug: rituximab

• Registration Number: NCT04002297
• Lead Sponsor: BeiGene

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-06-27
• Study First Submitted QC: 2019-06-27
• Study First Posted: 2019-06-28
• Study Start: 2019-08-20
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-20
• Last Update Posted: 2025-02-21
• Primary Completion: 2027-03
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 510

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A: zanubrutinib plus rituximab	zanubrutinib	Participants will receive zanubrutinib plus rituximab, followed by zanubrutinib monotherapy until Independent Review Committee (IRC)-confirmed disease progression.
Arm A: zanubrutinib plus rituximab	rituximab	Participants will receive zanubrutinib plus rituximab, followed by zanubrutinib monotherapy until Independent Review Committee (IRC)-confirmed disease progression.
Arm B: bendamustine plus rituximab	bendamustine	Participants will receive bendamustine plus rituximab, followed by observation.
Arm B: bendamustine plus rituximab	rituximab	Participants will receive bendamustine plus rituximab, followed by observation.

Primary Outcome Measures

Name	Time	Method
Progression-free survival (PFS) determined by independent central review	Up to approximately 7 years	PFS is defined as the time from randomization to the date of first documentation of disease progression or death, whichever occurs first.

Secondary Outcome Measures

Name	Time	Method
PFS by investigator assessment	Up to approximately 7 years	PFS is defined as the time from randomization to the date of first documentation of disease progression or death, whichever occurs first.
Overall response rate (ORR)	Up to approximately 7 years	ORR is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR), determined by independent central review and by investigator assessment.
Time to Response (TTR)	Up to approximately 7 years	TTR, as determined by independent central review and by investigator assessment, and defined as the time from randomization to the first documentation of response.
Rate of complete response (CR) or complete metabolic response	Up to approximately 7 years	Rate of CR or complete metabolic response is defined as the percentage of participants who achieve a CR or complete metabolic response, determined by independent central review and by investigator assessment.
Duration of response (DOR)	Up to approximately 7 years	DOR, as determined by independent central review and by investigator assessment, and defined as the time from the date that response criteria are first met to the date that disease progression is objectively documented or death, whichever occurs first.
Overall survival (OS)	Up to approximately 7 years	OS is defined as the time from randomization to the date of death due to any reason.
Participant-reported outcomes (PROs) as assessed by the European Quality of Life 5-Dimension 5 Level Questionnaire (EQ-5D-5L)	Up to approximately 7 years	EuroQoL-Five Dimensions, Five Levels (EQ-5D-5L) is a generic, self-reported measure of utility that consists of a five-item descriptive system and a visual analogue scale (EQ VAS). The descriptive system involves five health dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). Participants may choose from the following response levels: no problems=1; slight problems=2; moderate problems=3; severe problems=4; and unable to/extreme problems=5. Higher values indicate worst health.
PROs as assessed by the European Organization for Research on Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)	Up to approximately 7 years	The EORTC QLQ-30 contains 30 questions that incorporate 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The participant answers questions about their health during the past week. There are 28 questions answered on a 4-point scale where 1 =Not at all (best) to 4 =Very Much (worst) and 2 questions answered on a 7-point scale where 1 =Very poor (worst) to 7 =Excellent (best).
Number of participants with adverse events and serious adverse events	Up to approximately 7 years	Number of participants with adverse events and serious adverse events, including laboratory values, vital signs, and physical examination findings.

Trial Locations

Locations (176)

West Penn Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

Beijing Friendship Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China

Fujian Medical University Union Hospital; 🇨🇳 Fuzhou, Fujian, China

The Ottawa Hospital; 🇨🇦 Ottawa, Ontario, Canada

Sun Yat Sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China

Guangdong Provincial Peoples Hospital; 🇨🇳 Guangzhou, Guangdong, China

Harbin Medical University Cancer Hospital; 🇨🇳 Harbin, Heilongjiang, China

Henan Cancer Hospital; 🇨🇳 Zhengzhou, Henan, China

Hunan Cancer Hospital; 🇨🇳 Changsha, Hunan, China

The Affiliated Hospital of Xuzhou Medical University; 🇨🇳 Xuzhou, Jiangsu, China

Nanfang Hospital of Southern Medical University; 🇨🇳 Guangzhou, Guangdong, China

The First Affiliated Hospital of Nanchang University Branch Donghu; 🇨🇳 Nanchang, Jiangxi, China

The First Hospital of Jilin University; 🇨🇳 Changchun, Jilin, China

Shengjing Hospital of China Medical University; 🇨🇳 Shenyang, Liaoning, China

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China

The First Affiliated Hospital, Zhejiang University School of Medicine; 🇨🇳 Hangzhou, Zhejiang, China

Zhejiang Cancer Hospital; 🇨🇳 Hangzhou, Zhejiang, China

Centre de Lutte Contre Le Cancer Institut Bergonie; 🇫🇷 Bordeaux, France

West China Hospital, Sichuan University; 🇨🇳 Chengdu, Sichuan, China

Institute of Hematology and Hospital of Blood Disease; 🇨🇳 Tianjin, Tianjin, China

Tianjin Medical University Cancer Institute and Hospital; 🇨🇳 Tianjin, Tianjin, China

Affiliated Cancer Hospital of Xinjiang Medical University; 🇨🇳 Urumqi, Xinjiang, China

Chru de Brest Hospital Morvan; 🇫🇷 Brest, France

Chu Dijon; 🇫🇷 Dijon, France

Chu Grenoble Alpes; 🇫🇷 Grenoble Cedex, France

Institut Paoli Calmettes; 🇫🇷 Marseille, France

Centre Hospitalier Universitaire Nantes Hotel Dieu; 🇫🇷 Nantes Cedex, France

Institut Curie; 🇫🇷 Paris, France

Chu Hopital Lyon Sud; 🇫🇷 PierreBenite, France

Centre Hospitalier Le Mans; 🇫🇷 Le Mans, France

Hopital Claude Huriez Chu Lille; 🇫🇷 Lille, France

Centre Hospitalier Universitaire de Poitier Hopital de La Miletrie Hopital Jean Bernard; 🇫🇷 Poitiers, France

Ch Cornouaille; 🇫🇷 Quimper, France

Iuc Toulouse Oncopole; 🇫🇷 Toulouse, France

Universitatsklinikum Heidelberg; 🇩🇪 Heidelberg, Germany

Uniklinik Koln (Aor); 🇩🇪 Koln, Germany

Dept of Medicine Iii, University Hospitallmu; 🇩🇪 Munich, Germany

Universitaetsklinikum Ulm, Innere Medizin Iii; 🇩🇪 Ulm, Germany

Petrus Krankenhaus Wuppertal; 🇩🇪 Wuppertal, Germany

Cork University Hospital; 🇮🇪 Cork, Ireland

St Jamess Hospital; 🇮🇪 Dublin, Ireland

University Hospital Galway; 🇮🇪 Galway, Ireland

University Hospital Limerick; 🇮🇪 Limerick, Ireland

University Hospital Waterford; 🇮🇪 Waterford, Ireland

Azienda Ospedaliera Nazionale Ssantonio E Biagio E Cesare Arrigo; 🇮🇹 Alessandria, Italy

Policlinico Sorsola Malpighi, Aou Di Bologna; 🇮🇹 Bologna, Italy

Azienda Ospedaliera Universitaria San Martino; 🇮🇹 Genova, Italy

Niguarda Cancer Center Division of Hematology; 🇮🇹 Milano, Italy

Aou Maggiore Della Carita; 🇮🇹 Novara, Italy

Aoor Villa Sofia Cervello; 🇮🇹 Palermo, Italy

Aou Pisana, Stabilimento Di Santa Chiara; 🇮🇹 Pisa, Italy

Unita Di Ematologia, Dipartimento Di Ematologia Ed Oncologia; 🇮🇹 Ravenna, Italy

Azienda Unita Sanitaria Locale Irccs; 🇮🇹 Reggio Emilia, Italy

Universita Degli Studi La Sapienza; 🇮🇹 Roma, Italy

Aou Senese Policlinico Santa Maria Alle Scotte; 🇮🇹 Siena, Italy

Ao Citta Della Salute E Della Scienza Di Torino Presidio O; 🇮🇹 Torino, Italy

University of Verona; 🇮🇹 Verona, Italy

Chiba Cancer Center; 🇯🇵 Chibashi, Chiba, Japan

Hiroshima Red Cross Hospital and Atomic Bomb Survivors Hospital; 🇯🇵 Hiroshimashi, Hiroshima, Japan

Kanagawa Cancer Center; 🇯🇵 Yokohamashi, Kanagawa, Japan

Tohoku University Hospital; 🇯🇵 Sendaishi, Miyagi, Japan

Kurashiki Central Hospital; 🇯🇵 Kurashikishi, Okayama, Japan

Osaka Red Cross Hospital; 🇯🇵 Osakashi, Osaka, Japan

National Cancer Center Hospital; 🇯🇵 Chuoku, Tokyo, Japan

National Hospital Organization Okayama Medical Center; 🇯🇵 Okayama, Japan

Osaka Metropolitan University Hospital; 🇯🇵 Osaka, Japan

Tokyo Medical and Dental University Hospital; 🇯🇵 Tokyo, Japan

Yokohama Municipal Citizens Hospital; 🇯🇵 Yokohamashi, Japan

Hagaziekenhuis; 🇳🇱 Den Haag, Netherlands

Admiraal de Ruijter Ziekenhuis; 🇳🇱 Goes, Netherlands

University of Medical Center Groningen (Umcg); 🇳🇱 Groningen, Netherlands

St Antonius Ziekenhuis, Randd Interne Geneeskunde (F); 🇳🇱 Nieuwegein, Netherlands

Albert Schweitzer Ziekenhuis; 🇳🇱 Nijmegen, Netherlands

Erasmus Mc; 🇳🇱 Rotterdam, Netherlands

Christchurch Hospital (Canterbury Health Laboratories); 🇳🇿 Christchurch, New Zealand

Tauranga Hospital; 🇳🇿 Tauranga, New Zealand

Szpital Uniwersytecki Nr Im Dr Jana Biziela; 🇵🇱 Bydgoszcz, Poland

Silesian Healthy Blood Clinic; 🇵🇱 Chorzow, Poland

Uniwersyteckie Centrum Kliniczne; 🇵🇱 Gdansk, Poland

Copernicus Podmiot Leczniczy Sp Z Oo Wojewodzkie Centrum Onkologii; 🇵🇱 Gdask, Poland

Szpitale Pomorskie Spolka Z Ograniczona Odpowiedzialnoscia; 🇵🇱 Gdynia, Poland

Pratia McM Krakow; 🇵🇱 Krakow, Poland

Wojewodzki Szpital Specjalistyczny W Legnicy; 🇵🇱 Legnica, Poland

Wielospecjalistyczne Centrum Onkologii I Traumatologii Im M Kopernika W Lodzi; 🇵🇱 Lodz, Poland

Centrum Onkologii Ziemi Lubelskiej; 🇵🇱 Lublin, Poland

Specjalistyczny Szpital Im Dr Alfreda Sokolowskiego; 🇵🇱 Walbrzych, Poland

Instytut Hematologii I Transfuzjologii W Warszawie; 🇵🇱 Warszawa, Poland

Uniwersytecki Szpital Kliniczny Im Jana Mikulicza Radeckiego We Wroclawiu; 🇵🇱 Wroclaw, Poland

Chuln Hospital de Santa Maria; 🇵🇹 Lisboa, Portugal

Instituto Portugues Oncologia de Lisboa Francisco Gentil, Epe; 🇵🇹 Lisbon, Portugal

Centro Hospitalar Universitario Porto; 🇵🇹 Porto, Portugal

Instituto Portugues de Oncologia Do Porto Francisco Gentil, Epe; 🇵🇹 Porto, Portugal

Institutul Clinic Fundeni; 🇷🇴 Bucuresti, Romania

Institutul Regional de Oncologie Iasi; 🇷🇴 Iasi, Romania

Clinical Hospital, Sp Botkin; 🇷🇺 Moscow, Moskva, Russian Federation

Tr Trakya University Health Research and Application Center (Hospital); 🇹🇷 Edirne, Turkey

Fgu Russian Scientific Research Institute of Hematology and Transfusiology; 🇷🇺 Saint Petersburg, Sankt-Peterburg, Russian Federation

Leningrad Regional Clinic and Hospital; 🇷🇺 Saint Petersburg, Sankt-Peterburg, Russian Federation

Gbuz Mmcc Kommunarka Dzm; 🇷🇺 Moscow, Russian Federation

Hospital Universitario Vall Dhebron; 🇪🇸 Barcelona, Spain

Institut Catala Doncologia; 🇪🇸 Barcelona, Spain

Ico Hug Trias I Pujol; 🇪🇸 Barcelona, Spain

Ico Girona; 🇪🇸 Girona, Spain

Hospital Universitario Gregorio Maranon; 🇪🇸 Madrid, Spain

Md Anderson Cancer Center Madrid Spain; 🇪🇸 Madrid, Spain

Start Madrid Fundacion Jimenez Diaz; 🇪🇸 Madrid, Spain

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

Hospital Regional Universitario de Malaga; 🇪🇸 Malaga, Spain

Hospital Universitario Virgen Del Rocio; 🇪🇸 Sevilla, Spain

Tri Service General Hospital; 🇨🇳 Taipei, Taiwan

Dr Abdurrahman Yurtaslan Oncology Teaching and Research Hospital; 🇹🇷 Ankara, Turkey

Hematoloji Ve Hematolik Onkoloji Tani Ve Tedavi Merezi; 🇹🇷 Ankara, Turkey

Gazi University; 🇹🇷 Ankara, Turkey

Vkv American Hospital; 🇹🇷 Istanbul, Turkey

Mersin Universitesi Tip Fakultesi Hastanesi; 🇹🇷 Mersin, Turkey

Cherkasy Regional Oncology Dispensary; 🇺🇦 Cherkasy, Ukraine

Municipal Non Profit Enterprise City Clinical Hospital; 🇺🇦 Dnipro, Ukraine

National Cancer Institute; 🇺🇦 Kiev, Ukraine

Si Institute of Blood Pathology and Transfusion Medicine Nams of Ukraine, Hematology Department; 🇺🇦 Lviv, Ukraine

Aneurin Bevan University Health Board; 🇬🇧 Abergavenny, United Kingdom

Birmingham Heartlands Hospital; 🇬🇧 Birmingham, United Kingdom

Russells Hall Hopsital; 🇬🇧 Dudley, United Kingdom

Royal Marsden Nhs Foundation Royal Marsden Hospital; 🇬🇧 Sutton, United Kingdom

Providence Portland Medical Center; 🇺🇸 Portland, Oregon, United States

Calvary Mater Newcastle; 🇦🇺 Waratah, New South Wales, Australia

Icon Cancer Foundation; 🇦🇺 South Brisbane, Queensland, Australia

Royal Hobart Hospital; 🇦🇺 Hobart, Tasmania, Australia

Quanzhou First Affliated Hospital of Fujian Medical University; 🇨🇳 Quanzhou, Fujian, China

Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology; 🇨🇳 Wuhan, Hubei, China

Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School; 🇨🇳 Nanjing, Jiangsu, China

Jiangsu Province Hospital; 🇨🇳 Nanjing, Jiangsu, China

Jilin Cancer Hospital; 🇨🇳 Changchun, Jilin, China

Shanghai East Hospital; 🇨🇳 Shanghai, Shanghai, China

Hwa Mei Hospital, University of Chinese Academy of Sciences (Ningbo No Hospital); 🇨🇳 Ningbo, Zhejiang, China

Necker University Hospital; 🇫🇷 Paris, France

Mater Misericordiae University Hospital; 🇮🇪 Dublin, Ireland

National Hospital Organization Nagoya Medical Center; 🇯🇵 Nagoyashi, Aichi, Japan

Toyohashi Municipal Hospital; 🇯🇵 Toyohashi, Aichi, Japan

Kurume University Hospital; 🇯🇵 Kurume, Fukuoka, Japan

National Hospital Organization Kumamoto Medical Center; 🇯🇵 Kumamotoshi, Kumamoto, Japan

University Hospital, Kyoto Prefectural Univ of Medicine; 🇯🇵 Kyoto, Japan

National Cheng Kung University Hospital; 🇨🇳 Tainan, Taiwan

Chi Mei Hospital Liouying; 🇨🇳 Tainan, Taiwan

Chao Family Comprehensive Cancer Center; 🇺🇸 Orange, California, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

Beth Israel Deaconess Medical Center (Bidmc); 🇺🇸 Boston, Massachusetts, United States

University of Michigan Health System; 🇺🇸 Ann Arbor, Michigan, United States

Comprehensive Cancer Centers of Nevada; 🇺🇸 Las Vegas, Nevada, United States

Icahn School of Medicine At Mount Sinai; 🇺🇸 New York, New York, United States

Clinical Research Alliance, Inc; 🇺🇸 Westbury, New York, United States

The University of Texas Md Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Joe Arrington Cancer Research and Treatment Center; 🇺🇸 Lubbock, Texas, United States

Seattle Cancer Care Alliance; 🇺🇸 Seattle, Washington, United States

Canberra Hospital; 🇦🇺 Garran, Australian Capital Territory, Australia

Concord Repatriation General Hospital; 🇦🇺 Concord, New South Wales, Australia

The Tweed Valley Hospital; 🇦🇺 Cudgen, New South Wales, Australia

Saint Vincents Hospital Sydney; 🇦🇺 Darlinghurst, New South Wales, Australia

Gosford Hospital; 🇦🇺 Gosford, New South Wales, Australia

Sunshine Coast Hospital and Health Service; 🇦🇺 Birtinya, Queensland, Australia

Flinders Medical Centre; 🇦🇺 Bedford PK, South Australia, Australia

Monash Health; 🇦🇺 Clayton, Victoria, Australia

St Vincents Hospital Melbourne; 🇦🇺 Fitzroy, Victoria, Australia

Peninsula Private Hospital; 🇦🇺 Frankston, Victoria, Australia

Barwon Health the Geelong Hospital; 🇦🇺 Geelong, Victoria, Australia

Royal Perth Hospital; 🇦🇺 Perth, Western Australia, Australia

Ordensklinikum Linz Gmbh Elisabethinen; 🇦🇹 Linz, Austria

Universitatsklinik Fur Innere Medizin Iii Universitatsklinikum Der Pmu Landeskrankenhaus Salzburg; 🇦🇹 Salzburg, Austria

Medical University Vienna Oncology; 🇦🇹 Vienna, Austria

Az Sint Jan Brugge; 🇧🇪 Brugge, Belgium

Universitair Ziekenhuis Brussel; 🇧🇪 Brussels, Belgium

Uz Antwerpen; 🇧🇪 Edegem, Belgium

Az Groeninge Campus Loofstraat; 🇧🇪 Kortrijk, Belgium

Centre Hospitalier Universitaire (Chu) de Liege Site Du Sart Tilman; 🇧🇪 Liege, Belgium

Centre Hospitalier Universitaire Universite Catholique de Louvain Site Godinne; 🇧🇪 Yvoir, Belgium

Ciusss de Lestrie Chus; 🇨🇦 Sherbrooke, Quebec, Canada

Peking University Peoples Hospital; 🇨🇳 Beijing, Beijing, China