A Study Comparing Zanubrutinib With Bendamustine Plus Rituximab in Participants With Previously Untreated CLL or SLL (SEQUOIA)
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
About this trial
This is an interventional treatment trial for Chronic Lymphocytic Leukemia focused on measuring zanubrutinib, BTK inhibitor, bendamustine, rituximab, venetoclax, BGB-3111, Phase 3
Eligibility Criteria
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 trial.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Sites / Locations
- Georgetown University Medical Center
- Emory University
- Augusta University
- Northwestern University
- Montgomery Cancer Center
- Dana Farber Cancer Institute
- Research Medical Center - Kansas City
- Washington University
- Comprehensive Cancer Centers of Nevada
- Summit Medical Group, PA
- Mount Sinai
- Columbia University Medical Center
- Memorial Sloan Kettering Cancer Center
- University of Rochester
- Duke University Medical Center
- Oregon Health & Science University
- Prairie Lakes Healthcare System
- Tennessee Oncology - Centennial Clinic
- Joe Arrington Cancer Research and Treatment Center
- Texas Oncology - Tyler
- University of Virginia
- VA Puget Sound Health Care System, Pathology and Laboratory Medicine Services 113
- Fred Hutchinson Cancer Research Center
- Concord Hospital
- The Tweed Hospital
- Calvary Mater Newcastle Hospital
- Westmead Hospital
- Icon Cancer Care - Wesley
- Royal Brisbane and Women's Hospital
- Princess Alexandra Hospital
- Royal Adelaide Hospital
- The Queen Elizabeth Hospital
- Royal Hobart Hospital
- Monash Medical Centre
- Box Hill Hospital
- Peter MacCallum Cancer Centre
- Saint Vincent's Hospital Melbourne
- Peninsula Private Hospital
- Royal Perth Hospital
- Icon Cancer Care - South Brisbane
- Medizinische Universitätsklinik Innsbruck
- Allgemeines Krankenhaus der Stadt Linz
- Krankenhaus der Barmherzigen Schwestern Linz
- Universitätsklinik für Innere Medizin Salzburg
- Klinikum Wels-Grieskirchen
- GasthuisZusters Antwerpen Sint-Augustinus
- Centre Hospitalier Universitaire Universite Catholique de Louvain Site Godinne
- Cliniques du Sud-Luxembourg Site Clinique Saint-Joseph
- Universitair Ziekenhuis Brussel
- Universitair Ziekenhuis Gent
- Centre Hospitalier Universitaire (CHU) de Liège - Site du Sart Tilman
- Clinique Saint-Pierre
- Fakultní Nemocnice Brno
- Fakultní Nemocnice Hradec Králové - Ústav Klinické Imunologie a Alergologie
- Fakultní Nemocnice Olomouc
- Fakultní Nemocnice Ostrava
- Všeobecná Fakultní Nemocnice v Praze
- Centre Hospitalier Universitaire de Poitier- Hopital de la Miletrie - Hopital Jean Bernard
- Centre Hospitalier Victor Dupouy d'Argenteuil
- Institut Bergonié
- CHU de Caen Côte de Nacre
- Centre Hospitalier Départemental Vendée
- Centre Hospitalier Le Mans
- Centre Hospitalier Universitaire Limoges CHU de Limoges
- Centre Léon Bérard
- Institut Paoli Calmettes
- Centre Hospitalier Universitaire Nantes - Hotel Dieu
- Groupe Hospitalier Pitie-Salpetriere
- Groupe Hospitalier du Haut Leveque
- Centre hospitalier Lyon Sud
- Hôpital Robert Debré
- Hôpital Pontchaillou
- Centre Henri-Becquerel
- Centre Hospitalier Régional et Universitaire de Tours Hôpital Bretonneau
- Centre Hospitalier Universitaire de Nancy - Hôpital de Brabois
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
- Presidio Ospedale di Montichiari
- Presidio Ospedaliero di Gardone Val Trompia
- Azienda Ospedaliera Universitaria San Martino
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
- Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
- Ospedale San Raffaele
- Universita Degli Studi di Modena-Azienda Ospedaliere Policlinco
- Azienda Unita Sanitaria Locale di Ravenna
- Fondazione Policlinico Universitario Agostino Gemelli
- Universita degli Studi di Roma "La Sapienza" - Umberto I Policlinico di Roma
- Ospedale Casa Sollievo della Sofferenza
- Azienda Ospedaliera Santa Maria di Terni
- Azienda Ospedaliera Città della Salute e della Scienza di Torino
- North Shore Hospital
- Auckland City Hospital
- Palmerston North Hospital
- Christchurch Hospital
- Tauranga Hospital
- Wojewódzki Szpital Specjalistyczny w Legnicy
- Szpital Specjalistyczny w Brzozowie Podkarpacki Ośrodek Onkologiczny im. Ks. B. Markiewicza
- Samodzielny Publiczny Zakład Opieki Zdrowotnej Zespół Szpitali Miejskich
- Copernicus Podmiot Leczniczy Wojewódzkiego Centrum Onkologii
- Szpitale Pomorskie Spółka z ograniczoną odpowiedzialnością
- Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie, Oddział w Gliwicach
- Malopolskie Centrum Medyczne
- Centrum Onkologii Ziemi Lubelskiej
- Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Łodzi
- Sverdlovsk Regional Clinical Hospital #1
- Kaluga Regional Hospital
- Clinical Oncology Dispensary, Kazan
- Kemerovo Regional Clinical Hospital n.a. S.V. Belyaev
- City Clinical Hospital No. 52 of the Moscow Healthcare Department
- N. N. Blokhin Russian Cancer Research Center
- Nizhniy Novgorod Regional Clinical Hospital N.A.
- Penza Regional Oncology Dispensary
- Municipal Healthcare Institution "Clinical Medical Sanitary Establishment #1"
- Ryazan Regional Clinical Hospital
- FGU Russian Scientific Research Institute of Hematology and Transfusiology
- State Healthcare Institution Oncologic Dispensary No. 2 - Health Department of Krasnodar Region
- Tula Area Clinical Hospital
- State Budgetary Healthcare Institution "Volgograd Regional Clinical Oncology Dispensary #1"
- Central City Hospital # 7
- Institut Català d'Oncologia
- Hospital Universitari Parc Taulí
- Hospital del Mar
- Hospital Universitario Vall d'Hebron
- Institut Català d'Oncologia - L'Hospitalet de Llobregat
- Clinica Universidad de Navarra Madrid
- Hospital Universitario de La Princesa
- Hospital Universitario Ramón Y Cajal
- MD Anderson Cancer Center - Madrid
- Hospital Universitario Puerta de Hierro - Majadahonda
- Clínica Universidad de Navarra Pamplona
- Hospital Universitario La Fe
- Hospital de Día Quirónsalud Zaragoza
- Skånes Universitetssjukhus i Lund
- Södra Älvsborgs Sjukhus - Borås
- Sahlgrenska Universitetssjukhuset, Östra sjukhuset
- Sunderby Sjukhus
- Universitetssjukhuset Örebro
- Karolinska Universitetssjukhuset - Solna
- Uppsala Akademiska Sjukhus
- Hualien Tzu Chi Hospital
- Taipei Medical University - Shuang Ho Hospital
- Chi Mei Hospital Liouying
- National Taiwan University Hospital
- Heart of England NHS Foundation Trust
- Cambridge University Hospitals NHS Foundation Trust
- East Kent Hospitals University NHS Foundation Trust
- Sarah Cannon Research Institute London
- Maidstone and Tunbridge Wells NHS Trust
- The Christie NHS Foundation Trust
- The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust
- The Leeds Teaching Hospitals NHS Trust
- Barts and The London NHS Trust
- The Royal Marsden NHS Foundation Trust
- Norfolk and Norwich University Hospital
- Nottingham University Hospitals NHS Trust
- Derriford Hospital
- Southampton General Hospital
- City Hospitals Sunderland NHS Foundation Trust
- The Royal Marsden NHS Foundation Trust
- The Royal Wolverhampton NHS Trust
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Cohort 1, Arm A: Zanubrutinib
Cohort 1, Arm B: B+R
Cohort 1a, Arm A (China only): Zanubrutinib
Cohort 1a, Arm B (China only): B + R
Cohort 2, Arm C: Zanubrutinib
Cohort 3, Arm D: Venetoclax + zanubrutinib
Participants will receive zanubrutinib until unacceptable toxicity or disease progression
Participants will receive bendamustine plus rituximab for up to six 28-day cycles
Participants will receive zanubrutinib until unacceptable toxicity or disease progression
Participants will receive bendamustine plus rituximab for up to six 28-day cycles
Participants will receive zanubrutinib until unacceptable toxicity or disease progression
Approximately 110 participants, 50 without del17p and 60 with del[17p] or TP53 mutation will receive venetoclax until unacceptable toxicity, disease progression, or for maximum of 24 cycles; Participants will also receive zanubrutinib for a minimum of 27 cycles, or until unacceptable toxicity or disease progression, whichever occurs first. Each cycle is 28 days.