A Study Comparing Zanubrutinib With Bendamustine Plus Rituximab in Participants With Previously Untreated CLL or SLL (SEQUOIA)

An International, Phase 3, Open-Label, Randomized Study of BGB-3111 Compared With Bendamustine Plus Rituximab in Patients With Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (CLL/SLL)

To compare efficacy between zanubrutinib versus bendamustine and rituximab in patients with previously untreated CLL/SLL, as measured by progression free survival assess by Independent Central Review.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma
• Intervention / Treatment: Drug: Bendamustine; Drug: Rituximab; Drug: Zanubrutinib; Drug: Venetoclax

Detailed Description

This is a global phase 3, open label, randomized study of zanubrutinib versus bendamustine plus rituximab (B+R) in participants with previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL), including participants without del(17p) [Cohort 1] and participants with del(17p) [Cohort 2 and Cohort 3]. Participants in Cohort 1 are randomized 1:1 to zanubrutinib (Arm A) or bendamustine plus rituximab (Arm B). Randomization will be stratified by age, Binet stage, immunoglobulin variable region heavy chain (IGHV) mutational status, and geographic region. Participants in Cohort 2 will receive treatment with zanubrutinib. Participants in Cohort 3 will receive treatment with zanubrutinib and venetoclax.

• Study Type: Interventional
• Enrollment (Actual): 590
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • South Brisbane, Australia
    • Icon Cancer Care - South Brisbane
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Concord Hospital
    • Tweed Heads, New South Wales, Australia
      • The Tweed Hospital
    • Waratah, New South Wales, Australia
      • Calvary Mater Newcastle Hospital
    • Westmead, New South Wales, Australia
      • Westmead Hospital
  • Queensland
    • Auchenflower, Queensland, Australia
      • Icon Cancer Care - Wesley
    • Herston, Queensland, Australia
      • Royal Brisbane and Women'S Hospital
    • Woolloongabba, Queensland, Australia
      • Princess Alexandra Hospital
  • South Australia
    • Adelaide, South Australia, Australia
      • Royal Adelaide Hospital
    • Woodville South, South Australia, Australia
      • The Queen Elizabeth Hospital
  • Tasmania
    • Hobart, Tasmania, Australia
      • Royal Hobart Hospital
  • Victoria
    • Bentleigh East, Victoria, Australia
      • Monash Medical Centre
    • Box Hill, Victoria, Australia
      • Box Hill Hospital
    • East Melbourne, Victoria, Australia
      • Peter MacCallum Cancer Centre
    • Fitzroy, Victoria, Australia
      • Saint Vincent's Hospital Melbourne
    • Frankston, Victoria, Australia
      • Peninsula Private Hospital
  • Western Australia
    • Perth, Western Australia, Australia
      • Royal Perth Hospital
• Austria
  • Innsbruck, Austria
    • Medizinische Universitätsklinik Innsbruck
  • Linz, Austria
    • Krankenhaus der Barmherzigen Schwestern Linz
  • Linz, Austria
    • Allgemeines Krankenhaus der Stadt Linz
  • Salzburg, Austria
    • Universitätsklinik für Innere Medizin Salzburg
  • Wels, Austria
    • Klinikum Wels-Grieskirchen
• Belgium
  • Arlon, Belgium
    • Cliniques du Sud-Luxembourg Site Clinique Saint-Joseph
  • Brussels, Belgium
    • Universitair Ziekenhuis Brussel
  • Gent, Belgium
    • Universitair Ziekenhuis Gent
  • Liège, Belgium
    • Centre Hospitalier Universitaire (CHU) de Liege - Site du Sart Tilman
  • Ottignies, Belgium
    • Clinique Saint-Pierre
  • Antwerpen
    • Wilrijk, Antwerpen, Belgium
      • GasthuisZusters Antwerpen Sint-Augustinus
  • Namur
    • Yvoir, Namur, Belgium
      • Centre Hospitalier Universitaire Universite Catholique de Louvain Site Godinne
• China
  • Anhui
    • Hefei, Anhui, China, 230000
      • Anhui Provincial Hospital
  • Beijing
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital
    • Beijing, Beijing, China, 100050
      • Beijing Friendship Hospital, Capital Medical University
    • Beijing, Beijing, China, 100000
      • Peking University Third Hospital
  • Chongqing
    • Chongqing, Chongqing, China, 400037
      • Xinqiao Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Fujian Medical University Union Hospital
    • Quanzhou, Fujian, China, 362000
      • Quanzhou First Affiliated Hospital of Fujian Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong Provincial People's Hospital
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
  • Jiangsu
    • Nanjing, Jiangsu, China, 290029
      • Jiangsu Province Hospital
    • Suzhou, Jiangsu, China, 215006
      • The First Affiliated Hospital of Soochow University Branch Shizi
    • Wuxi, Jiangsu, China, 214023
      • Wuxi People's Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of Nanchang University Branch Donghu
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital
    • Tianjin, Tianjin, China, 300020
      • Institute of Hematology and Hospital of Blood Disease
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital, Zhejiang University School of Medicine
• Czechia
  • Brno, Czechia
    • Fakultní Nemocnice Brno
  • Hradec Králové, Czechia
    • Fakultní Nemocnice Hradec Králové - Ústav Klinické Imunologie a Alergologie
  • Olomouc, Czechia
    • Fakultni Nemocnice Olomouc
  • Ostrava-Poruba, Czechia
    • Fakultni Nemocnice Ostrava
  • Praha, Czechia
    • Vseobecna fakultni nemocnice v Praze
• France
  • Argenteuil, France
    • Centre Hospitalier Victor Dupouy d'Argenteuil
  • Bordeaux, France
    • Institut Bergonié
  • Caen, France
    • CHU de Caen Côte de Nacre
  • La Roche sur Yon, France
    • Centre Hospitalier Departemental Vendée
  • Le Mans, France
    • Centre Hospitalier Le Mans
  • Limoges, France
    • Centre Hospitalier Universitaire Limoges CHU de Limoges
  • Lyon, France
    • Centre Léon Bérard
  • Marseille, France
    • Institut Paoli Calmettes
  • Nantes, France
    • Centre Hospitalier Universitaire Nantes - Hotel Dieu
  • Paris, France
    • Groupe Hospitalier Pitie-Salpetriere
  • Pessac, France
    • Groupe Hospitalier du Haut Leveque
  • Pierre-Bénite, France
    • Centre Hospitalier Lyon Sud
  • Reims, France
    • Hopital Robert Debre
  • Rennes, France
    • Hôpital Pontchaillou
  • Rouen, France
    • Centre Henri-Becquerel
  • Tours, France
    • Centre Hospitalier Régional et Universitaire de Tours Hôpital Bretonneau
  • Vandoeuvre-lès-Nancy, France
    • Centre Hospitalier Universitaire de Nancy - Hopital de Brabois
  • Poitou-charentes
    • Poitiers Cedex, Poitou-charentes, France
      • Centre Hospitalier Universitaire de Poitier- Hopital de la Miletrie - Hopital Jean Bernard
• Italy
  • Brescia, Italy
    • Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
  • Brescia, Italy
    • Presidio Ospedale di Montichiari
  • Brescia, Italy
    • Presidio Ospedaliero di Gardone Val Trompia
  • Genova, Italy
    • Azienda Ospedaliera Universitaria San Martino
  • Meldola, Italy
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
  • Milano, Italy
    • Ospedale San Raffaele
  • Milano, Italy
    • Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico
  • Milano, Italy
    • Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
  • Modena, Italy
    • Universita Degli Studi di Modena-Azienda Ospedaliere Policlinco
  • Ravenna, Italy
    • Azienda Unita Sanitaria Locale Di Ravenna
  • Roma, Italy
    • Fondazione Policlinico Universitario Agostino Gemelli
  • Roma, Italy
    • Universita degli Studi di Roma "La Sapienza" - Umberto I Policlinico di Roma
  • San Giovanni Rotondo, Italy
    • Ospedale Casa Sollievo della Sofferenza
  • Terni, Italy
    • Azienda Ospedaliera Santa Maria di Terni
  • Torino, Italy
    • Azienda Ospedaliera Citta della Salute e della Scienza di Torino
• New Zealand
  • Christchurch, New Zealand
    • Christchurch Hospital
  • Tauranga, New Zealand
    • Tauranga Hospital
  • Auckland
    • North Shore, Auckland, New Zealand
      • North Shore Hospital
  • Aukland
    • Grafton, Aukland, New Zealand
      • Auckland City Hospital
  • Manawatu-wanganui
    • Palmerston North, Manawatu-wanganui, New Zealand
      • Palmerston North Hospital
• Poland
  • Brzozów, Poland
    • Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. ks. B. Markiewicza
  • Chorzów, Poland
    • Samodzielny Publiczny Zakład Opieki Zdrowotnej Zespół Szpitali Miejskich
  • Gdańsk, Poland
    • Copernicus Podmiot Leczniczy Wojewódzkiego Centrum Onkologii
  • Gdynia, Poland
    • Szpitale Pomorskie Spółka Z Ograniczoną Odpowiedzialnością
  • Gliwice, Poland
    • Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie, Oddział w Gliwicach
  • Kraków, Poland
    • Malopolskie Centrum Medyczne
  • Lublin, Poland
    • Centrum Onkologii Ziemi Lubelskiej
  • Łódź, Poland
    • Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Łodzi
  • Dolnoslaskie
    • Legnica, Dolnoslaskie, Poland
      • Wojewodzki Szpital Specjalistyczny w Legnicy
• Russian Federation
  • Ekaterinburg, Russian Federation
    • Sverdlovsk Regional Clinical Hospital #1
  • Kaluga, Russian Federation
    • Kaluga Regional Hospital
  • Kazan, Russian Federation
    • Clinical Oncology Dispensary, Kazan
  • Kemerovo, Russian Federation
    • Kemerovo Regional Clinical Hospital n.a. S.V. Belyaev
  • Moscow, Russian Federation
    • N. N. Blokhin Russian Cancer Research Center
  • Moscow, Russian Federation
    • City Clinical Hospital No. 52 of the Moscow Healthcare Department
  • Nizhny Novgorod, Russian Federation
    • Nizhniy Novgorod Regional Clinical Hospital N.A.
  • Penza, Russian Federation
    • Penza Regional Oncology Dispensary
  • Perm, Russian Federation
    • Municipal Healthcare Institution "Clinical Medical Sanitary Establishment #1"
  • Ryazan, Russian Federation
    • Ryazan Regional Clinical Hospital
  • Saint Petersburg, Russian Federation
    • FGU Russian Scientific Research Institute of Hematology and Transfusiology
  • Sochi, Russian Federation
    • State Healthcare Institution Oncologic Dispensary No. 2 - Health Department of Krasnodar Region
  • Tula, Russian Federation
    • Tula Area Clinical Hospital
  • Volgograd, Russian Federation
    • State Budgetary Healthcare Institution "Volgograd Regional Clinical Oncology Dispensary #1"
  • Yekaterinburg, Russian Federation
    • Central City Hospital # 7
• Spain
  • Barcelona, Spain
    • Hospital Del Mar
  • Barcelona, Spain
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain
    • Institut Català d'Oncologia - L'Hospitalet de Llobregat
  • Madrid, Spain
    • Hospital Universitario de La Princesa
  • Madrid, Spain
    • Hospital Universitario Ramon Y Cajal
  • Madrid, Spain
    • Clinica Universidad de Navarra Madrid
  • Madrid, Spain
    • MD Anderson Cancer Center - Madrid
  • Majadahonda, Spain
    • Hospital Universitario Puerta de Hierro - Majadahonda
  • Pamplona, Spain
    • Clinica Universidad de Navarra Pamplona
  • Valencia, Spain
    • Hospital Universitario La Fe
  • Zaragoza, Spain
    • Hospital de Día Quirónsalud Zaragoza
  • Barcelona
    • Badalona, Barcelona, Spain
      • Institut Catala d'Oncologia
    • Sabadell, Barcelona, Spain
      • Hospital Universitari Parc Tauli
• Sweden
  • Lulea, Sweden
    • Sunderby Sjukhus
  • Orebro, Sweden
    • Universitetssjukhuset Örebro
  • Stockholm, Sweden
    • Karolinska Universitetssjukhuset - Solna
  • Uppsala, Sweden
    • Uppsala Akademiska Sjukhus
  • Skane
    • Lund, Skane, Sweden
      • Skånes Universitetssjukhus i Lund
  • Vastra Gotaland
    • Borås, Vastra Gotaland, Sweden
      • Södra Älvsborgs Sjukhus - Borås
    • Göteborg, Vastra Gotaland, Sweden
      • Sahlgrenska Universitetssjukhuset, Östra sjukhuset
• Taiwan
  • Hualien City, Taiwan
    • Hualien Tzu Chi Hospital
  • New Taipei City, Taiwan
    • Taipei Medical University - Shuang Ho Hospital
  • Tainan City, Taiwan
    • Chi Mei Hospital Liouying
  • Taipei, Taiwan
    • National Taiwan University Hospital
• United Kingdom
  • Bournemouth, United Kingdom
    • The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust
  • Leeds, United Kingdom
    • The Leeds Teaching Hospitals NHS Trust
  • London, United Kingdom
    • Barts and the London NHS Trust
  • London, United Kingdom
    • The Royal Marsden NHS Foundation Trust
  • Norwich, United Kingdom
    • Norfolk and Norwich University Hospital
  • Nottingham, United Kingdom
    • Nottingham University Hospitals NHS Trust
  • Plymouth, United Kingdom
    • Derriford Hospital
  • Southampton, United Kingdom
    • Southampton General Hospital
  • Sunderland, United Kingdom
    • City Hospitals Sunderland NHS Foundation Trust
  • Sutton, United Kingdom
    • The Royal Marsden NHS Foundation Trust
  • Wolverhampton, United Kingdom
    • The Royal Wolverhampton NHS Trust
  • England
    • Birmingham, England, United Kingdom
      • Heart of England NHS Foundation Trust
    • Cambridge, England, United Kingdom
      • Cambridge University Hospitals NHS Foundation Trust
    • Canterbury, England, United Kingdom
      • East Kent Hospitals University NHS Foundation Trust
    • London, England, United Kingdom
      • Sarah Cannon Research Institute London
    • Maidstone, England, United Kingdom
      • Maidstone and Tunbridge Wells NHS Trust
    • Manchester, England, United Kingdom
      • The Christie NHS Foundation Trust
• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Illinois
    • Chicago, Illinois, United States, 60208
      • Northwestern University
  • Kentucky
    • Mount Sterling, Kentucky, United States, 40353
      • Montgomery Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • Research Medical Center - Kansas City
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • Nevada
    • Las Vegas, Nevada, United States, 89014
      • Comprehensive Cancer Centers of Nevada
  • New Jersey
    • Florham Park, New Jersey, United States, 07932
      • Summit Medical Group, PA
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10029
      • Mount Sinai
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • South Dakota
    • Watertown, South Dakota, United States, 57201
      • Prairie Lakes Healthcare System
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology - Centennial Clinic
  • Texas
    • Lubbock, Texas, United States, 79410
      • Joe Arrington Cancer Research and Treatment Center
    • Tyler, Texas, United States, 75702
      • Texas Oncology - Tyler
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98108
      • VA Puget Sound Health Care System, Pathology and Laboratory Medicine Services 113

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Unsuitable for chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR)
• Confirmed diagnosis of CD20-positive CLL or SLL, requiring treatment
• Measurable disease by imaging
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Life expectancy ≥ 6 months
• Adequate bone marrow function
• Adequate renal and hepatic function

Key Exclusion Criteria:

• Previous systemic treatment for CLL/SLL
• Requires ongoing need for corticosteroid treatment
• Known prolymphocytic leukemia or history of or suspected Richter's transformation.
• Clinically significant cardiovascular disease
• Prior malignancy within the past 3 years, except for curatively treated basal or squamous cell skin cancer, non-muscle-invasive bladder cancer, carcinoma in situ of the cervix of breast, or localized Gleason score 6 prostate cancer
• History of severe bleeding disorder
• History of stroke or intracranial hemorrhage within 6 months before the first dose of study drug
• Severe or debilitating pulmonary disease
• Inability to swallow capsules or disease affecting gastrointestinal function
• Active infection requiring systemic treatment
• Known central nervous system involvement by leukemia or lymphoma
• Underlying medical condition that will render the administration of study drug hazardous or obscure interpretation of toxicity or AEs
• Known infection with human immunodeficiency virus (HIV) or active hepatitis B or C infection
• Major surgery ≤ 4 weeks prior to start of study treatment
• Pregnant or nursing females
• Vaccination with live vaccine within 35 days prior to the first dose of study drug.
• Ongoing alcohol or drug addiction
• Known hypersensitivity to zanubrutinib, bendamustine, rituximab, or venetoclax (as applicable) or any other ingredients of the study drugs
• Requires ongoing treatment with strong cytochrome P450 (CYP3A) inhibitor or inducer
• Concurrent participation in another therapeutic clinical study

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Bendamustine + Rituximab; Participants will receive bendamustine plus rituximab for up to six 28-day cycles (Arm B)	Drug: Bendamustine; Administered intravenously (IV) at a dose of 90 mg/m^2/day on the first 2 days of each cycle for 6 cycles.; Other Names: Treanda, Ribomustin, and Levact; Drug: Rituximab; Administered intravenously (IV) at a dose of 375 mg/m^2 on day 0 of cycle 1, and at a dose of 500 mg/m^2 on day 1 of cycles 2 to 6; Other Names: Rituxan, MabThera
Experimental: Cohort 1: Zanubrutinib; Participants will receive zanubrutinib until unacceptable toxicity or disease progression (Arm A)	Drug: Zanubrutinib; Administered as two 80-milligram (mg) capsules by mouth twice a day (160 mg twice a day); Other Names: BGB-3111; BRUKINSA
Experimental: Cohort 1a (China only): Bendamustine + Rituximab; Participants will receive bendamustine plus rituximab for up to six 28-day cycles (Arm B, China only)	Drug: Bendamustine; Administered intravenously (IV) at a dose of 90 mg/m^2/day on the first 2 days of each cycle for 6 cycles.; Other Names: Treanda, Ribomustin, and Levact; Drug: Rituximab; Administered intravenously (IV) at a dose of 375 mg/m^2 on day 0 of cycle 1, and at a dose of 500 mg/m^2 on day 1 of cycles 2 to 6; Other Names: Rituxan, MabThera
Experimental: Cohort 1a (China only): Zanubrutinib; Participants will receive zanubrutinib until unacceptable toxicity or disease progression (Arm A, China only)	Drug: Zanubrutinib; Administered as two 80-milligram (mg) capsules by mouth twice a day (160 mg twice a day); Other Names: BGB-3111; BRUKINSA
Experimental: Cohort 2: Zanubrutinib; Participants will receive zanubrutinib until unacceptable toxicity or disease progression (Arm C)	Drug: Zanubrutinib; Administered as two 80-milligram (mg) capsules by mouth twice a day (160 mg twice a day); Other Names: BGB-3111; BRUKINSA
Experimental: Cohort 3: Venetoclax + Zanubrutinib; Approximately 110 participants, 50 without del17p and 60 with del[17p] or TP53 mutation will receive zanubrutinib plus venetoclax; Participants will also receive zanubrutinib starting on Cycle 1 Day 1 then daily for a minimum of 27 cycles, or until unacceptable toxicity or disease progression, whichever occurs first. Participants will receive venetoclax starting Cycle 4 Day 1 according to a 5-week dose-up schedule then daily until unacceptable toxicity, disease progression, or for a maximum of 24 cycles. Each cycle is 28 days. (Arm D)	Drug: Zanubrutinib; Administered as two 80-milligram (mg) capsules by mouth twice a day (160 mg twice a day); Other Names: BGB-3111; BRUKINSA; Drug: Venetoclax; 400 mg tablets administered orally once daily.; Other Names: Venclexta, Venclyxto

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort 1: Progression-free Survival (PFS) as Determined by Independent Central Review (ICR)	PFS is defined as the time from randomization until first documentation of progression or death from any cause, whichever occurs first, as assessed by the ICR per 2008 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines with modifications for treatment-related lymphocytosis in participants with CLL and the Revised Criteria for Response for Malignant Lymphoma in participants with small lymphocytic lymphoma (SLL).	Up to approximately 3 years and 7 months (as of cut-off date of 07MAY2021)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort 1: Overall Response Rate (ORR) Between Treatment Groups as Determined by ICR	ORR in Cohort 1 is defined as the percentage of participants who achieve a complete response, complete response with incomplete bone marrow recovery, partial response, or partial response with lymphocytosis, determined by the ICR.	Up to 5 years
Pooled Cohort 1/1a: Overall Response Rate (ORR) Between Treatment Groups		Up to 5 years
Cohort 1: Overall Survival (OS) Between Treatment Groups as Determined by the ICR	OS in Cohort 1 is defined as the time from randomization to the date of death due to any reason.	Up to 5 years
Cohort 1: Duration of Response (DOR) Between Treatment Groups as Determined by the ICR	Duration of response in Cohort 1 determined using the iwCLL criteria with modification for treatment related lymphocytosis (in participants with CLL) and the Lugano Classification for non-Hodgkin lymphoma (NHL; in participants with SLL), is defined as the time from the date that criteria for response (ie, partial response with lymphocytosis [PR-L] or better) are first met to the date that disease progression is objectively documented or death, whichever occurs first.	Up to 5 years
Pooled Cohort 1/1a: Duration of Response (DOR) Between Treatment Groups		Up to 5 years
Cohort 1: Progression-free Survival (PFS) Between Treatment Groups Determined by Investigator Assessment (IA)	PFS is defined as the time from randomization until first documentation of progression or death from any cause, whichever occurs first, as assessed by the investigator per iwCLL guidelines with modifications for treatment-related lymphocytosis in participants with CLL and the Revised Criteria for Response for Malignant Lymphoma in participants with SLL.	Up to 5 years
Pooled Cohort 1/1a: Progression-free Survival (PFS) Between Treatment Groups Determined by Investigator Assessment (IA)		Up to 5 years
Cohort 1: Patient-reported Outcomes as Assessed by the (European Quality Of Life 5D 5L) EQ-5D-5L Questionnaire		Up to 5 years
Cohort 1: Patient-reported Outcomes as Assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Questionnaire.		Up to 5 years
Cohort 2: Overall Response Rate (ORR)		Up to 5 years
Cohort 2: Progression-free Survival (PFS)		Up to 5 years
Cohort 2: Duration of Response (DOR)		Up to 5 years
Cohort 3: Overall Response Rate (ORR)		Up to 5 years
Cohort 3: Progression-free Survival (PFS)		Up to 5 years
Cohort 3: Duration of Response (DOR)		Up to 5 years
Cohort 3: Rate of Undetectable Minimal Residual Disease (MRD4)		Up to 5 years
Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs)		Up to 5 years
Apparent Rate of Clearance of Zanubrutinib From Plasma (CL/F)CL/F		Predose up to 12 hours postdose
Cohort 1 Zanubrutinib Only Arms: Area-Under-Curve From Time 0 to 12 Hours Postdose (AUC0-12)		Predose up to 12 hours postdose
Cohort 3: Area-Under-Curve From Time 0 to 12 Hours Postdose (AUC0-12) of Zanubrutinib		Predose up to 12 hours postdose

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Study Director: Study Director, BeiGene

Publications and helpful links

General Publications

• Mu S, Tang Z, Novotny W, Tawashi M, Li TK, Ou Y, Sahasranaman S. Effect of rifampin and itraconazole on the pharmacokinetics of zanubrutinib (a Bruton's tyrosine kinase inhibitor) in Asian and non-Asian healthy subjects. Cancer Chemother Pharmacol. 2020 Feb;85(2):391-399. doi: 10.1007/s00280-019-04015-w. Epub 2019 Dec 26.
• Tam CS, Robak T, Ghia P, Kahl BS, Walker P, Janowski W, Simpson D, Shadman M, Ganly PS, Laurenti L, Opat S, Tani M, Ciepluch H, Verner E, Simkovic M, Osterborg A, Trneny M, Tedeschi A, Paik JC, Kuwahara SB, Feng S, Ramakrishnan V, Cohen A, Huang J, Hillmen P, Brown JR. Zanubrutinib monotherapy for patients with treatment naive chronic lymphocytic leukemia and 17p deletion. Haematologica. 2020 Oct 13;106(9):2354-2363. doi: 10.3324/haematol.2020.259432.
• Tam CS, Brown JR, Kahl BS, Ghia P, Giannopoulos K, Jurczak W, Simkovic M, Shadman M, Osterborg A, Laurenti L, Walker P, Opat S, Chan H, Ciepluch H, Greil R, Tani M, Trneny M, Brander DM, Flinn IW, Grosicki S, Verner E, Tedeschi A, Li J, Tian T, Zhou L, Marimpietri C, Paik JC, Cohen A, Huang J, Robak T, Hillmen P. Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial. Lancet Oncol. 2022 Aug;23(8):1031-1043. doi: 10.1016/S1470-2045(22)00293-5. Epub 2022 Jul 7. Erratum In: Lancet Oncol. 2023 Mar;24(3):e106.

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2017
• Primary Completion (Actual): May 7, 2021
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: November 1, 2017
• First Submitted That Met QC Criteria: November 7, 2017
• First Posted (Actual): November 8, 2017

Study Record Updates

• Last Update Posted (Estimated): November 9, 2023
• Last Update Submitted That Met QC Criteria: November 7, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: rituximab; venetoclax; Phase 3; BTK inhibitor; BGB-3111; bendamustine; zanubrutinib
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Leukemia, B-Cell; Chronic Disease; Lymphoma; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Venetoclax; Bendamustine Hydrochloride; Rituximab; Zanubrutinib
• Other Study ID Numbers: BGB-3111-304; 2017-001551-31 (EudraCT Number); CTR20190416 (Registry Identifier: Center for drug evaluation, NMPA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No