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

Sponsor

BeiGene (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03336333

Collaborator

(none)

740

Enrollment

160

Locations

Arms

83.9

Anticipated Duration (Months)

4.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma	Drug: Zanubrutinib Drug: Bendamustine Drug: Rituximab Drug: Venetoclax	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

740 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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)

Actual Study Start Date :

Nov 2, 2017

Actual Primary Completion Date :

May 31, 2022

Anticipated Study Completion Date :

Oct 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1, Arm A: Zanubrutinib Participants will receive zanubrutinib until unacceptable toxicity or disease progression	Drug: Zanubrutinib Administered as two 80-mg capsules by mouth twice a day (160 mg twice a day) Other Names: BGB-3111 BRUKINSA
Experimental: Cohort 1, Arm B: B+R Participants will receive bendamustine plus rituximab for up to six 28-day cycles	Drug: Bendamustine Administered intravenously (IV) at a dose of 90 mg/m2/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/m2 on day 0 of cycle 1, and at a dose of 500 mg/m2 on day 1 of cycles 2 to 6. Other Names: Rituxan, MabThera
Experimental: Cohort 1a, Arm A (China only): Zanubrutinib Participants will receive zanubrutinib until unacceptable toxicity or disease progression	Drug: Zanubrutinib Administered as two 80-mg capsules by mouth twice a day (160 mg twice a day) Other Names: BGB-3111 BRUKINSA
Experimental: Cohort 1a, Arm B (China only): B + R Participants will receive bendamustine plus rituximab for up to six 28-day cycles	Drug: Bendamustine Administered intravenously (IV) at a dose of 90 mg/m2/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/m2 on day 0 of cycle 1, and at a dose of 500 mg/m2 on day 1 of cycles 2 to 6. Other Names: Rituxan, MabThera
Experimental: Cohort 2, Arm C: Zanubrutinib Participants will receive zanubrutinib until unacceptable toxicity or disease progression	Drug: Zanubrutinib Administered as two 80-mg capsules by mouth twice a day (160 mg twice a day) Other Names: BGB-3111 BRUKINSA
Experimental: Cohort 3, Arm D: Venetoclax + zanubrutinib 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.	Drug: Zanubrutinib Administered as two 80-mg capsules by mouth twice a day (160 mg twice a day) Other Names: BGB-3111 BRUKINSA Drug: Venetoclax 400mg tablets administered orally once daily. Other Names: Venclexta, Venclyxto

Outcome Measures

Primary Outcome Measures

Cohort 1: Progression-free survival (PFS) between treatment groups (Zanubrutinib vs. B+R) as determined by independent central review (ICR). [Up to 5 years]

Secondary Outcome Measures

Cohort 1: Overall response rate (ORR) between treatment groups [Up to 5 years]
Pooled Cohort 1/1a: Overall response rate (ORR) between treatment groups [Up to 5 yearsl]
Cohort 1: Overall survival (OS) between treatment groups [Up to 5 years.]
Cohort 1: Duration of response (DOR) between treatment groups [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). [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) [Up to 5 years.]
Number of participants experiencing 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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Georgetown University Medical Center	Washington	District of Columbia	United States	20007
2	Emory University	Atlanta	Georgia	United States	30322
3	Augusta University	Augusta	Georgia	United States	30912
4	Northwestern University	Chicago	Illinois	United States	60208
5	Montgomery Cancer Center	Mount Sterling	Kentucky	United States	40353
6	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
7	Research Medical Center - Kansas City	Kansas City	Missouri	United States	64132
8	Washington University	Saint Louis	Missouri	United States	63110
9	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89014
10	Summit Medical Group, PA	Florham Park	New Jersey	United States	07932
11	Mount Sinai	New York	New York	United States	10029
12	Columbia University Medical Center	New York	New York	United States	10032
13	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
14	University of Rochester	Rochester	New York	United States	14642
15	Duke University Medical Center	Durham	North Carolina	United States	27705
16	Oregon Health & Science University	Portland	Oregon	United States	97239
17	Prairie Lakes Healthcare System	Watertown	South Dakota	United States	57201
18	Tennessee Oncology - Centennial Clinic	Nashville	Tennessee	United States	37203
19	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas	United States	79410
20	Texas Oncology - Tyler	Tyler	Texas	United States	75702
21	University of Virginia	Charlottesville	Virginia	United States	22908
22	VA Puget Sound Health Care System, Pathology and Laboratory Medicine Services 113	Seattle	Washington	United States	98108
23	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
24	Concord Hospital	Concord	New South Wales	Australia	2139
25	The Tweed Hospital	Tweed Heads	New South Wales	Australia
26	Calvary Mater Newcastle Hospital	Waratah	New South Wales	Australia
27	Westmead Hospital	Westmead	New South Wales	Australia
28	Icon Cancer Care - Wesley	Auchenflower	Queensland	Australia
29	Royal Brisbane and Women's Hospital	Herston	Queensland	Australia
30	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia
31	Royal Adelaide Hospital	Adelaide	South Australia	Australia
32	The Queen Elizabeth Hospital	Woodville South	South Australia	Australia
33	Royal Hobart Hospital	Hobart	Tasmania	Australia
34	Monash Medical Centre	Bentleigh East	Victoria	Australia
35	Box Hill Hospital	Box Hill	Victoria	Australia
36	Peter MacCallum Cancer Centre	East Melbourne	Victoria	Australia
37	Saint Vincent's Hospital Melbourne	Fitzroy	Victoria	Australia
38	Peninsula Private Hospital	Frankston	Victoria	Australia
39	Royal Perth Hospital	Perth	Western Australia	Australia
40	Icon Cancer Care - South Brisbane	South Brisbane		Australia
41	Medizinische Universitätsklinik Innsbruck	Innsbruck		Austria
42	Allgemeines Krankenhaus der Stadt Linz	Linz		Austria
43	Krankenhaus der Barmherzigen Schwestern Linz	Linz		Austria
44	Universitätsklinik für Innere Medizin Salzburg	Salzburg		Austria
45	Klinikum Wels-Grieskirchen	Wels		Austria
46	GasthuisZusters Antwerpen Sint-Augustinus	Wilrijk	Antwerpen	Belgium
47	Centre Hospitalier Universitaire Universite Catholique de Louvain Site Godinne	Yvoir	Namur	Belgium
48	Cliniques du Sud-Luxembourg Site Clinique Saint-Joseph	Arlon		Belgium
49	Universitair Ziekenhuis Brussel	Brussels		Belgium
50	Universitair Ziekenhuis Gent	Gent		Belgium
51	Centre Hospitalier Universitaire (CHU) de Liège - Site du Sart Tilman	Liège		Belgium
52	Clinique Saint-Pierre	Ottignies		Belgium
53	Fakultní Nemocnice Brno	Brno		Czechia
54	Fakultní Nemocnice Hradec Králové - Ústav Klinické Imunologie a Alergologie	Hradec Králové		Czechia
55	Fakultní Nemocnice Olomouc	Olomouc		Czechia
56	Fakultní Nemocnice Ostrava	Ostrava-Poruba		Czechia
57	Všeobecná Fakultní Nemocnice v Praze	Praha		Czechia
58	Centre Hospitalier Universitaire de Poitier- Hopital de la Miletrie - Hopital Jean Bernard	Poitiers Cedex	Poitou-charentes	France
59	Centre Hospitalier Victor Dupouy d'Argenteuil	Argenteuil		France
60	Institut Bergonié	Bordeaux		France
61	CHU de Caen Côte de Nacre	Caen		France
62	Centre Hospitalier Départemental Vendée	La Roche sur Yon		France
63	Centre Hospitalier Le Mans	Le Mans		France
64	Centre Hospitalier Universitaire Limoges CHU de Limoges	Limoges		France
65	Centre Léon Bérard	Lyon		France
66	Institut Paoli Calmettes	Marseille		France
67	Centre Hospitalier Universitaire Nantes - Hotel Dieu	Nantes		France
68	Groupe Hospitalier Pitie-Salpetriere	Paris		France
69	Groupe Hospitalier du Haut Leveque	Pessac		France
70	Centre hospitalier Lyon Sud	Pierre-Bénite		France
71	Hôpital Robert Debré	Reims		France
72	Hôpital Pontchaillou	Rennes		France
73	Centre Henri-Becquerel	Rouen		France
74	Centre Hospitalier Régional et Universitaire de Tours Hôpital Bretonneau	Tours		France
75	Centre Hospitalier Universitaire de Nancy - Hôpital de Brabois	Vandoeuvre-lès-Nancy		France
76	Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia	Brescia		Italy
77	Presidio Ospedale di Montichiari	Brescia		Italy
78	Presidio Ospedaliero di Gardone Val Trompia	Brescia		Italy
79	Azienda Ospedaliera Universitaria San Martino	Genova		Italy
80	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori	Meldola		Italy
81	Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda	Milano		Italy
82	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano		Italy
83	Ospedale San Raffaele	Milano		Italy
84	Universita Degli Studi di Modena-Azienda Ospedaliere Policlinco	Modena		Italy
85	Azienda Unita Sanitaria Locale di Ravenna	Ravenna		Italy
86	Fondazione Policlinico Universitario Agostino Gemelli	Roma		Italy
87	Universita degli Studi di Roma "La Sapienza" - Umberto I Policlinico di Roma	Roma		Italy
88	Ospedale Casa Sollievo della Sofferenza	San Giovanni Rotondo		Italy
89	Azienda Ospedaliera Santa Maria di Terni	Terni		Italy
90	Azienda Ospedaliera Città della Salute e della Scienza di Torino	Torino		Italy
91	North Shore Hospital	North Shore	Auckland	New Zealand
92	Auckland City Hospital	Grafton	Aukland	New Zealand
93	Palmerston North Hospital	Palmerston North	Manawatu-wanganui	New Zealand
94	Christchurch Hospital	Christchurch		New Zealand
95	Tauranga Hospital	Tauranga		New Zealand
96	Wojewódzki Szpital Specjalistyczny w Legnicy	Legnica	Dolnoslaskie	Poland
97	Szpital Specjalistyczny w Brzozowie Podkarpacki Ośrodek Onkologiczny im. Ks. B. Markiewicza	Brzozów		Poland
98	Samodzielny Publiczny Zakład Opieki Zdrowotnej Zespół Szpitali Miejskich	Chorzów		Poland
99	Copernicus Podmiot Leczniczy Wojewódzkiego Centrum Onkologii	Gdańsk		Poland
100	Szpitale Pomorskie Spółka z ograniczoną odpowiedzialnością	Gdynia		Poland
101	Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie, Oddział w Gliwicach	Gliwice		Poland
102	Malopolskie Centrum Medyczne	Kraków		Poland
103	Centrum Onkologii Ziemi Lubelskiej	Lublin		Poland
104	Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Łodzi	Łódź		Poland
105	Sverdlovsk Regional Clinical Hospital #1	Ekaterinburg		Russian Federation
106	Kaluga Regional Hospital	Kaluga		Russian Federation
107	Clinical Oncology Dispensary, Kazan	Kazan		Russian Federation
108	Kemerovo Regional Clinical Hospital n.a. S.V. Belyaev	Kemerovo		Russian Federation
109	City Clinical Hospital No. 52 of the Moscow Healthcare Department	Moscow		Russian Federation
110	N. N. Blokhin Russian Cancer Research Center	Moscow		Russian Federation
111	Nizhniy Novgorod Regional Clinical Hospital N.A.	Nizhny Novgorod		Russian Federation
112	Penza Regional Oncology Dispensary	Penza		Russian Federation
113	Municipal Healthcare Institution "Clinical Medical Sanitary Establishment #1"	Perm		Russian Federation
114	Ryazan Regional Clinical Hospital	Ryazan		Russian Federation
115	FGU Russian Scientific Research Institute of Hematology and Transfusiology	Saint Petersburg		Russian Federation
116	State Healthcare Institution Oncologic Dispensary No. 2 - Health Department of Krasnodar Region	Sochi		Russian Federation
117	Tula Area Clinical Hospital	Tula		Russian Federation
118	State Budgetary Healthcare Institution "Volgograd Regional Clinical Oncology Dispensary #1"	Volgograd		Russian Federation
119	Central City Hospital # 7	Yekaterinburg		Russian Federation
120	Institut Català d'Oncologia	Badalona	Barcelona	Spain
121	Hospital Universitari Parc Taulí	Sabadell	Barcelona	Spain
122	Hospital del Mar	Barcelona		Spain
123	Hospital Universitario Vall d'Hebron	Barcelona		Spain
124	Institut Català d'Oncologia - L'Hospitalet de Llobregat	Barcelona		Spain
125	Clinica Universidad de Navarra Madrid	Madrid		Spain
126	Hospital Universitario de La Princesa	Madrid		Spain
127	Hospital Universitario Ramón Y Cajal	Madrid		Spain
128	MD Anderson Cancer Center - Madrid	Madrid		Spain
129	Hospital Universitario Puerta de Hierro - Majadahonda	Majadahonda		Spain
130	Clínica Universidad de Navarra Pamplona	Pamplona		Spain
131	Hospital Universitario La Fe	Valencia		Spain
132	Hospital de Día Quirónsalud Zaragoza	Zaragoza		Spain
133	Skånes Universitetssjukhus i Lund	Lund	Skane	Sweden
134	Södra Älvsborgs Sjukhus - Borås	Borås	Vastra Gotaland	Sweden
135	Sahlgrenska Universitetssjukhuset, Östra sjukhuset	Göteborg	Vastra Gotaland	Sweden
136	Sunderby Sjukhus	Lulea		Sweden
137	Universitetssjukhuset Örebro	Orebro		Sweden
138	Karolinska Universitetssjukhuset - Solna	Stockholm		Sweden
139	Uppsala Akademiska Sjukhus	Uppsala		Sweden
140	Hualien Tzu Chi Hospital	Hualien City		Taiwan
141	Taipei Medical University - Shuang Ho Hospital	New Taipei City		Taiwan
142	Chi Mei Hospital Liouying	Tainan City		Taiwan
143	National Taiwan University Hospital	Taipei		Taiwan
144	Heart of England NHS Foundation Trust	Birmingham	England	United Kingdom
145	Cambridge University Hospitals NHS Foundation Trust	Cambridge	England	United Kingdom
146	East Kent Hospitals University NHS Foundation Trust	Canterbury	England	United Kingdom
147	Sarah Cannon Research Institute London	London	England	United Kingdom
148	Maidstone and Tunbridge Wells NHS Trust	Maidstone	England	United Kingdom
149	The Christie NHS Foundation Trust	Manchester	England	United Kingdom
150	The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust	Bournemouth		United Kingdom
151	The Leeds Teaching Hospitals NHS Trust	Leeds		United Kingdom
152	Barts and The London NHS Trust	London		United Kingdom
153	The Royal Marsden NHS Foundation Trust	London		United Kingdom
154	Norfolk and Norwich University Hospital	Norwich		United Kingdom
155	Nottingham University Hospitals NHS Trust	Nottingham		United Kingdom
156	Derriford Hospital	Plymouth		United Kingdom
157	Southampton General Hospital	Southampton		United Kingdom
158	City Hospitals Sunderland NHS Foundation Trust	Sunderland		United Kingdom
159	The Royal Marsden NHS Foundation Trust	Sutton		United Kingdom
160	The Royal Wolverhampton NHS Trust	Wolverhampton		United Kingdom