--- title: 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 nct_id: NCT04002297 overall_status: ACTIVE_NOT_RECRUITING phase: PHASE3 sponsor: BeiGene study_type: INTERVENTIONAL primary_condition: Mantle Cell Lymphoma; Non-Hodgkin Lymphoma countries: United States, Australia, Austria, Belgium, Canada, China, France, Germany, Ireland, Italy, Japan, Netherlands, New Zealand, Poland, Portugal, Romania, Russia, Spain, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom canonical_url: "https://parkinsonspathways.com/agent/trials/NCT04002297.md" clinicaltrials_gov: "https://clinicaltrials.gov/study/NCT04002297" ct_last_update_post_date: 2025-09-26 last_seen_at: "2026-05-12T06:54:06.485Z" source: ClinicalTrials.gov (mirrored, no enrichment) --- # 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 **NCT ID:** [NCT04002297](https://clinicaltrials.gov/study/NCT04002297) ## Key Facts - **Status:** ACTIVE_NOT_RECRUITING - **Phase:** PHASE3 - **Study Type:** INTERVENTIONAL - **Target Enrollment:** 510 - **Lead Sponsor:** BeiGene - **Conditions:** Mantle Cell Lymphoma; Non-Hodgkin Lymphoma - **Start Date:** 2019-08-20 - **Completion Date:** 2027-12 - **CT.gov Last Update:** 2025-09-26 ## 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 - **Minimum age:** 60 Years - **Sex:** ALL - **Healthy Volunteers:** No ``` 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. ``` ## Arms - **Arm A: zanubrutinib plus rituximab** (EXPERIMENTAL) — Participants will receive zanubrutinib plus rituximab, followed by zanubrutinib monotherapy until Independent Review Committee (IRC)-confirmed disease progression. - **Arm B: bendamustine plus rituximab** (ACTIVE_COMPARATOR) — Participants will receive bendamustine plus rituximab, followed by observation. ## Interventions - **zanubrutinib** (DRUG) — Administered as two 80 mg capsules by mouth twice a day - **bendamustine** (DRUG) — Administered intravenously at a dose of 90 mg/m2/day on Days 1 and 2 of Cycles 1 to 6 - **rituximab** (DRUG) — Administered intravenously at a dose of 375 mg/m2 on Day 1 of Cycles 1 to 6 ## Primary Outcomes - **Progression-free survival (PFS) determined by independent central review** _(time frame: 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 Outcomes - **PFS by investigator assessment** _(time frame: Up to approximately 7 years)_ - **Overall response rate (ORR)** _(time frame: Up to approximately 7 years)_ - **Duration of response (DOR)** _(time frame: Up to approximately 7 years)_ - **Overall survival (OS)** _(time frame: Up to approximately 7 years)_ - **Time to Response (TTR)** _(time frame: Up to approximately 7 years)_ - **Rate of complete response (CR) or complete metabolic response** _(time frame: Up to approximately 7 years)_ - **Participant-reported outcomes (PROs) as assessed by the European Quality of Life 5-Dimension 5 Level Questionnaire (EQ-5D-5L)** _(time frame: Up to approximately 7 years)_ - **PROs as assessed by the European Organization for Research on Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)** _(time frame: Up to approximately 7 years)_ - **Number of participants with adverse events and serious adverse events** _(time frame: Up to approximately 7 years)_ ## Locations (176) - 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 - Providence Portland Medical Center, Portland, Oregon, United States - West Penn Hospital, Pittsburgh, Pennsylvania, 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 - Calvary Mater Newcastle, Waratah, New South Wales, Australia - Sunshine Coast Hospital and Health Service, Birtinya, Queensland, Australia - Icon Cancer Foundation, South Brisbane, Queensland, Australia - Flinders Medical Centre, Bedford PK, South Australia, Australia - Royal Hobart Hospital, Hobart, Tasmania, 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, Bruges, 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, Liège, Belgium - Centre Hospitalier Universitaire Universite Catholique de Louvain Site Godinne, Yvoir, Belgium - The Ottawa Hospital, Ottawa, Ontario, Canada - Ciusss de Lestrie Chus, Sherbrooke, Quebec, Canada - Peking University Peoples Hospital, Beijing, Beijing Municipality, China - Beijing Friendship Hospital, Capital Medical University, Beijing, Beijing Municipality, China - Fujian Medical University Union Hospital, Fuzhou, Fujian, China - Quanzhou First Affliated Hospital of Fujian Medical University, Quanzhou, Fujian, China - Sun Yat Sen University Cancer Center, Guangzhou, Guangdong, China - Guangdong Provincial Peoples Hospital, Guangzhou, Guangdong, China - Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong, China - Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China - Henan Cancer Hospital, Zhengzhou, Henan, China - Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology, Wuhan, Hubei, China - Hunan Cancer Hospital, Changsha, Hunan, China - Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China - Jiangsu Province Hospital, Nanjing, Jiangsu, China - The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China - The First Affiliated Hospital of Nanchang University Branch Donghu, Nanchang, Jiangxi, China - Jilin Cancer Hospital, Changchun, Jilin, 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 Municipality, China - Shanghai East Hospital, Shanghai, Shanghai Municipality, China - West China Hospital, Sichuan University, Chengdu, Sichuan, China - Institute of Hematology and Hospital of Blood Disease, Tianjin, Tianjin Municipality, China - Tianjin Medical University Cancer Institute and Hospital, Tianjin, Tianjin Municipality, China - Affiliated Cancer Hospital of Xinjiang Medical University, Ürümqi, Xinjiang, China - The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China - Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China - Hwa Mei Hospital, University of Chinese Academy of Sciences (Ningbo No Hospital), Ningbo, Zhejiang, China - Centre de Lutte Contre Le Cancer Institut Bergonie, Bordeaux, France - Chru de Brest Hospital Morvan, Brest, France - Chu Dijon, Dijon, France - Chu Grenoble Alpes, Grenoble, France - Centre Hospitalier Le Mans, Le Mans, France - Hopital Claude Huriez Chu Lille, Lille, France - Institut Paoli Calmettes, Marseille, France - Centre Hospitalier Universitaire Nantes Hotel Dieu, Nantes, France - Institut Curie, Paris, France - Necker University Hospital, Paris, France - Chu Hopital Lyon Sud, PierreBenite, France - Centre Hospitalier Universitaire de Poitier Hopital de La Miletrie Hopital Jean Bernard, Poitiers, France - Ch Cornouaille, Quimper, France - Iuc Toulouse Oncopole, Toulouse, France - Uniklinik Koln (Aor), Cologne, Germany - Universitatsklinikum Heidelberg, Heidelberg, 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 - Mater Misericordiae University Hospital, Dublin, 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, Milan, 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 - National Hospital Organization Nagoya Medical Center, Nagoya, Aichi-ken, Japan - Toyohashi Municipal Hospital, Toyohashi, Aichi-ken, Japan - Chiba Cancer Center, Chiba, Chiba, Japan - Kurume University Hospital, Kurume, Fukuoka, Japan - Hiroshima Red Cross Hospital and Atomic Bomb Survivors Hospital, Hiroshima, Hiroshima, Japan - Kanagawa Cancer Center, Yokohama, Kanagawa, Japan - National Hospital Organization Kumamoto Medical Center, Kumamoto, Kumamoto, Japan - Tohoku University Hospital, Sendai, Miyagi, Japan - Kurashiki Central Hospital, Kurashikishi, Okayama-ken, Japan - Osaka Red Cross Hospital, Osakashi, Osaka, Japan - National Cancer Center Hospital, Chuoku, Tokyo, Japan - University Hospital, Kyoto Prefectural Univ of Medicine, Kyoto, 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, Yokohama, Japan - 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 - Hagaziekenhuis, The Hague, 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, Chorzów, 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 - Instytut Hematologii I Transfuzjologii W Warszawie, Warsaw, Poland - Specjalistyczny Szpital Im Dr Alfreda Sokolowskiego, Wałbrzych, Poland - Uniwersytecki Szpital Kliniczny Im Jana Mikulicza Radeckiego We Wroclawiu, Wroclaw, Poland - Instituto Portugues Oncologia de Lisboa Francisco Gentil, Epe, Lisbon, Portugal - Chuln Hospital de Santa Maria, Lisbon, Portugal - Centro Hospitalar Universitario Porto, Porto, Portugal - Instituto Portugues de Oncologia Do Porto Francisco Gentil, Epe, Porto, Portugal - Institutul Clinic Fundeni, Bucharest, Romania - Institutul Regional de Oncologie Iasi, Iași, Romania - Clinical Hospital, Sp Botkin, Moscow, Moscow, Russia - Fgu Russian Scientific Research Institute of Hematology and Transfusiology, Saint Petersburg, Sankt-Peterburg, Russia - Leningrad Regional Clinic and Hospital, Saint Petersburg, Sankt-Peterburg, Russia - Gbuz Mmcc Kommunarka Dzm, Moscow, Russia - 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, Málaga, Spain - Hospital Universitario Virgen Del Rocio, Seville, Spain - National Cheng Kung University Hospital, Tainan, Taiwan - Chi Mei Hospital Liouying, Tainan, Taiwan - Tri Service General Hospital, Taipei, Taiwan - Dr Abdurrahman Yurtaslan Oncology Teaching and Research Hospital, Ankara, Turkey (Türkiye) - Hematoloji Ve Hematolik Onkoloji Tani Ve Tedavi Merezi, Ankara, Turkey (Türkiye) - Gazi University, Ankara, Turkey (Türkiye) - Tr Trakya University Health Research and Application Center (Hospital), Edirne, Turkey (Türkiye) - Vkv American Hospital, Istanbul, Turkey (Türkiye) - Mersin Universitesi Tip Fakultesi Hastanesi, Mersin, Turkey (Türkiye) - 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 ## Recent Field Changes (last 30 days) - `status.overallStatus` — added _(2026-05-12)_ - `status.primaryCompletionDate` — added _(2026-05-12)_ - `status.completionDate` — added _(2026-05-12)_ - `status.lastUpdatePostDate` — added _(2026-05-12)_ - `design.phases` — added _(2026-05-12)_ - `design.enrollmentCount` — added _(2026-05-12)_ - `eligibility.criteria` — added _(2026-05-12)_ - `eligibility.minAge` — added _(2026-05-12)_ - `eligibility.sex` — added _(2026-05-12)_ - `outcomes.primary` — added _(2026-05-12)_ - `outcomes.secondary` — added _(2026-05-12)_ - `armsInterventions.arms` — added _(2026-05-12)_ - `armsInterventions.interventions` — added _(2026-05-12)_ - `sponsor.lead` — added _(2026-05-12)_ - `results.hasResults` — added _(2026-05-12)_ - `locations.chao family comprehensive cancer center|orange|california|united states` — added _(2026-05-12)_ - `locations.rush university medical center|chicago|illinois|united states` — added _(2026-05-12)_ - `locations.beth israel deaconess medical center (bidmc)|boston|massachusetts|united states` — added _(2026-05-12)_ - `locations.university of michigan health system|ann arbor|michigan|united states` — added _(2026-05-12)_ - `locations.comprehensive cancer centers of nevada|las vegas|nevada|united states` — added _(2026-05-12)_ - `locations.icahn school of medicine at mount sinai|new york|new york|united states` — added _(2026-05-12)_ - `locations.clinical research alliance, inc|westbury|new york|united states` — added _(2026-05-12)_ - `locations.providence portland medical center|portland|oregon|united states` — added _(2026-05-12)_ - `locations.west penn hospital|pittsburgh|pennsylvania|united states` — added _(2026-05-12)_ - `locations.the university of texas md anderson cancer center|houston|texas|united states` — added _(2026-05-12)_ - `locations.joe arrington cancer research and treatment center|lubbock|texas|united states` — added _(2026-05-12)_ - `locations.seattle cancer care alliance|seattle|washington|united states` — added _(2026-05-12)_ - `locations.canberra hospital|garran|australian capital territory|australia` — added _(2026-05-12)_ - `locations.concord repatriation general hospital|concord|new south wales|australia` — added _(2026-05-12)_ - `locations.the tweed valley hospital|cudgen|new south wales|australia` — added _(2026-05-12)_ - `locations.saint vincents hospital sydney|darlinghurst|new south wales|australia` — added _(2026-05-12)_ - `locations.gosford hospital|gosford|new south wales|australia` — added _(2026-05-12)_ - `locations.calvary mater newcastle|waratah|new south wales|australia` — added _(2026-05-12)_ - `locations.sunshine coast hospital and health service|birtinya|queensland|australia` — added _(2026-05-12)_ - `locations.icon cancer foundation|south brisbane|queensland|australia` — added _(2026-05-12)_ - `locations.flinders medical centre|bedford pk|south australia|australia` — added _(2026-05-12)_ - `locations.royal hobart hospital|hobart|tasmania|australia` — added _(2026-05-12)_ - `locations.monash health|clayton|victoria|australia` — added _(2026-05-12)_ - `locations.st vincents hospital melbourne|fitzroy|victoria|australia` — added _(2026-05-12)_ - `locations.peninsula private hospital|frankston|victoria|australia` — added _(2026-05-12)_ - `locations.barwon health the geelong hospital|geelong|victoria|australia` — added _(2026-05-12)_ - `locations.royal perth hospital|perth|western australia|australia` — added _(2026-05-12)_ - `locations.ordensklinikum linz gmbh elisabethinen|linz||austria` — added _(2026-05-12)_ - `locations.peking university peoples hospital|beijing|beijing municipality|china` — added _(2026-05-12)_ - `locations.universitatsklinik fur innere medizin iii universitatsklinikum der pmu landeskrankenhaus salzburg|salzburg||austria` — added _(2026-05-12)_ - `locations.medical university vienna oncology|vienna||austria` — added _(2026-05-12)_ - `locations.az sint jan brugge|bruges||belgium` — added _(2026-05-12)_ - `locations.universitair ziekenhuis brussel|brussels||belgium` — added _(2026-05-12)_ - `locations.uz antwerpen|edegem||belgium` — added _(2026-05-12)_ - `locations.az groeninge campus loofstraat|kortrijk||belgium` — added _(2026-05-12)_ --- *Canonical: https://parkinsonspathways.com/agent/trials/NCT04002297.md* *Source data (authoritative): https://clinicaltrials.gov/study/NCT04002297* *This page is a raw mirror with no AI summary, no editorial enrichment, and no Parkinson's-specific filtering.*