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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03336333




Registration number
NCT03336333
Ethics application status
Date submitted
1/11/2017
Date registered
8/11/2017
Date last updated
9/11/2023

Titles & IDs
Public title
A Study Comparing Zanubrutinib With Bendamustine Plus Rituximab in Participants With Previously Untreated CLL or SLL
Scientific 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)
Secondary ID [1] 0 0
2017-001551-31
Secondary ID [2] 0 0
BGB-3111-304
Universal Trial Number (UTN)
Trial acronym
SEQUOIA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Lymphocytic Leukemia 0 0
Small Lymphocytic Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Zanubrutinib
Treatment: Drugs - Bendamustine
Treatment: Drugs - Rituximab
Treatment: Drugs - Venetoclax

Experimental: Cohort 1: Bendamustine + Rituximab - Participants will receive bendamustine plus rituximab for up to six 28-day cycles (Arm B)

Experimental: Cohort 1: Zanubrutinib - Participants will receive zanubrutinib until unacceptable toxicity or disease progression (Arm A)

Experimental: Cohort 1a (China only): Bendamustine + Rituximab - Participants will receive bendamustine plus rituximab for up to six 28-day cycles (Arm B, China only)

Experimental: Cohort 1a (China only): Zanubrutinib - Participants will receive zanubrutinib until unacceptable toxicity or disease progression (Arm A, China only)

Experimental: Cohort 2: Zanubrutinib - Participants will receive zanubrutinib until unacceptable toxicity or disease progression (Arm C)

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)


Treatment: Drugs: Zanubrutinib
Administered as two 80-milligram (mg) capsules by mouth twice a day (160 mg twice a day)

Treatment: Drugs: Bendamustine
Administered intravenously (IV) at a dose of 90 mg/m^2/day on the first 2 days of each cycle for 6 cycles.

Treatment: Drugs: 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

Treatment: Drugs: Venetoclax
400 mg tablets administered orally once daily.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Cohort 1: Progression-free Survival (PFS) as Determined by Independent Central Review (ICR)
Timepoint [1] 0 0
Up to approximately 3 years and 7 months (as of cut-off date of 07MAY2021)
Secondary outcome [1] 0 0
Cohort 1: Overall Response Rate (ORR) Between Treatment Groups as Determined by ICR
Timepoint [1] 0 0
Up to 5 years
Secondary outcome [2] 0 0
Pooled Cohort 1/1a: Overall Response Rate (ORR) Between Treatment Groups
Timepoint [2] 0 0
Up to 5 years
Secondary outcome [3] 0 0
Cohort 1: Overall Survival (OS) Between Treatment Groups as Determined by the ICR
Timepoint [3] 0 0
Up to 5 years
Secondary outcome [4] 0 0
Cohort 1: Duration of Response (DOR) Between Treatment Groups as Determined by the ICR
Timepoint [4] 0 0
Up to 5 years
Secondary outcome [5] 0 0
Pooled Cohort 1/1a: Duration of Response (DOR) Between Treatment Groups
Timepoint [5] 0 0
Up to 5 years
Secondary outcome [6] 0 0
Cohort 1: Progression-free Survival (PFS) Between Treatment Groups Determined by Investigator Assessment (IA)
Timepoint [6] 0 0
Up to 5 years
Secondary outcome [7] 0 0
Pooled Cohort 1/1a: Progression-free Survival (PFS) Between Treatment Groups Determined by Investigator Assessment (IA)
Timepoint [7] 0 0
Up to 5 years
Secondary outcome [8] 0 0
Cohort 1: Patient-reported Outcomes as Assessed by the (European Quality Of Life 5D 5L) EQ-5D-5L Questionnaire
Timepoint [8] 0 0
Up to 5 years
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
Up to 5 years
Secondary outcome [10] 0 0
Cohort 2: Overall Response Rate (ORR)
Timepoint [10] 0 0
Up to 5 years
Secondary outcome [11] 0 0
Cohort 2: Progression-free Survival (PFS)
Timepoint [11] 0 0
Up to 5 years
Secondary outcome [12] 0 0
Cohort 2: Duration of Response (DOR)
Timepoint [12] 0 0
Up to 5 years
Secondary outcome [13] 0 0
Cohort 3: Overall Response Rate (ORR)
Timepoint [13] 0 0
Up to 5 years
Secondary outcome [14] 0 0
Cohort 3: Progression-free Survival (PFS)
Timepoint [14] 0 0
Up to 5 years
Secondary outcome [15] 0 0
Cohort 3: Duration of Response (DOR)
Timepoint [15] 0 0
Up to 5 years
Secondary outcome [16] 0 0
Cohort 3: Rate of Undetectable Minimal Residual Disease (MRD4)
Timepoint [16] 0 0
Up to 5 years
Secondary outcome [17] 0 0
Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [17] 0 0
Up to 5 years
Secondary outcome [18] 0 0
Apparent Rate of Clearance of Zanubrutinib From Plasma (CL/F)CL/F
Timepoint [18] 0 0
Predose up to 12 hours postdose
Secondary outcome [19] 0 0
Cohort 1 Zanubrutinib Only Arms: Area-Under-Curve From Time 0 to 12 Hours Postdose (AUC0-12)
Timepoint [19] 0 0
Predose up to 12 hours postdose
Secondary outcome [20] 0 0
Cohort 3: Area-Under-Curve From Time 0 to 12 Hours Postdose (AUC0-12) of Zanubrutinib
Timepoint [20] 0 0
Predose up to 12 hours postdose

Eligibility
Key inclusion criteria
Key

- 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/10/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/09/2026
Actual
Sample size
Target
Accrual to date
Final
590
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Concord Hospital - Concord
Recruitment hospital [2] 0 0
The Tweed Hospital - Tweed Heads
Recruitment hospital [3] 0 0
Calvary Mater Newcastle Hospital - Waratah
Recruitment hospital [4] 0 0
Westmead Hospital - Westmead
Recruitment hospital [5] 0 0
Icon Cancer Care - Wesley - Auchenflower
Recruitment hospital [6] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [7] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [8] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [9] 0 0
The Queen Elizabeth Hospital - Woodville South
Recruitment hospital [10] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [11] 0 0
Monash Medical Centre - Bentleigh East
Recruitment hospital [12] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [13] 0 0
Peter MacCallum Cancer Centre - East Melbourne
Recruitment hospital [14] 0 0
Saint Vincent's Hospital Melbourne - Fitzroy
Recruitment hospital [15] 0 0
Peninsula Private Hospital - Frankston
Recruitment hospital [16] 0 0
Royal Perth Hospital - Perth
Recruitment hospital [17] 0 0
Icon Cancer Care - South Brisbane - South Brisbane
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
- Tweed Heads
Recruitment postcode(s) [3] 0 0
- Waratah
Recruitment postcode(s) [4] 0 0
- Westmead
Recruitment postcode(s) [5] 0 0
- Auchenflower
Recruitment postcode(s) [6] 0 0
- Herston
Recruitment postcode(s) [7] 0 0
- Woolloongabba
Recruitment postcode(s) [8] 0 0
- Adelaide
Recruitment postcode(s) [9] 0 0
- Woodville South
Recruitment postcode(s) [10] 0 0
- Hobart
Recruitment postcode(s) [11] 0 0
- Bentleigh East
Recruitment postcode(s) [12] 0 0
- Box Hill
Recruitment postcode(s) [13] 0 0
- East Melbourne
Recruitment postcode(s) [14] 0 0
- Fitzroy
Recruitment postcode(s) [15] 0 0
- Frankston
Recruitment postcode(s) [16] 0 0
- Perth
Recruitment postcode(s) [17] 0 0
- South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
District of Columbia
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Kentucky
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
Nevada
Country [8] 0 0
United States of America
State/province [8] 0 0
New Jersey
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Oregon
Country [12] 0 0
United States of America
State/province [12] 0 0
South Dakota
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Virginia
Country [16] 0 0
United States of America
State/province [16] 0 0
Washington
Country [17] 0 0
Austria
State/province [17] 0 0
Innsbruck
Country [18] 0 0
Austria
State/province [18] 0 0
Linz
Country [19] 0 0
Austria
State/province [19] 0 0
Salzburg
Country [20] 0 0
Austria
State/province [20] 0 0
Wels
Country [21] 0 0
Belgium
State/province [21] 0 0
Antwerpen
Country [22] 0 0
Belgium
State/province [22] 0 0
Namur
Country [23] 0 0
Belgium
State/province [23] 0 0
Arlon
Country [24] 0 0
Belgium
State/province [24] 0 0
Brussels
Country [25] 0 0
Belgium
State/province [25] 0 0
Gent
Country [26] 0 0
Belgium
State/province [26] 0 0
Liège
Country [27] 0 0
Belgium
State/province [27] 0 0
Ottignies
Country [28] 0 0
China
State/province [28] 0 0
Anhui
Country [29] 0 0
China
State/province [29] 0 0
Beijing
Country [30] 0 0
China
State/province [30] 0 0
Chongqing
Country [31] 0 0
China
State/province [31] 0 0
Fujian
Country [32] 0 0
China
State/province [32] 0 0
Guangdong
Country [33] 0 0
China
State/province [33] 0 0
Henan
Country [34] 0 0
China
State/province [34] 0 0
Hubei
Country [35] 0 0
China
State/province [35] 0 0
Jiangsu
Country [36] 0 0
China
State/province [36] 0 0
Jiangxi
Country [37] 0 0
China
State/province [37] 0 0
Jilin
Country [38] 0 0
China
State/province [38] 0 0
Sichuan
Country [39] 0 0
China
State/province [39] 0 0
Tianjin
Country [40] 0 0
China
State/province [40] 0 0
Zhejiang
Country [41] 0 0
Czechia
State/province [41] 0 0
Brno
Country [42] 0 0
Czechia
State/province [42] 0 0
Hradec Králové
Country [43] 0 0
Czechia
State/province [43] 0 0
Olomouc
Country [44] 0 0
Czechia
State/province [44] 0 0
Ostrava-Poruba
Country [45] 0 0
Czechia
State/province [45] 0 0
Praha
Country [46] 0 0
France
State/province [46] 0 0
Poitou-charentes
Country [47] 0 0
France
State/province [47] 0 0
Argenteuil
Country [48] 0 0
France
State/province [48] 0 0
Bordeaux
Country [49] 0 0
France
State/province [49] 0 0
Caen
Country [50] 0 0
France
State/province [50] 0 0
La Roche sur Yon
Country [51] 0 0
France
State/province [51] 0 0
Le Mans
Country [52] 0 0
France
State/province [52] 0 0
Limoges
Country [53] 0 0
France
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Lyon
Country [54] 0 0
France
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Marseille
Country [55] 0 0
France
State/province [55] 0 0
Nantes
Country [56] 0 0
France
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Paris
Country [57] 0 0
France
State/province [57] 0 0
Pessac
Country [58] 0 0
France
State/province [58] 0 0
Pierre-Bénite
Country [59] 0 0
France
State/province [59] 0 0
Reims
Country [60] 0 0
France
State/province [60] 0 0
Rennes
Country [61] 0 0
France
State/province [61] 0 0
Rouen
Country [62] 0 0
France
State/province [62] 0 0
Tours
Country [63] 0 0
France
State/province [63] 0 0
Vandoeuvre-lès-Nancy
Country [64] 0 0
Italy
State/province [64] 0 0
Brescia
Country [65] 0 0
Italy
State/province [65] 0 0
Genova
Country [66] 0 0
Italy
State/province [66] 0 0
Meldola
Country [67] 0 0
Italy
State/province [67] 0 0
Milano
Country [68] 0 0
Italy
State/province [68] 0 0
Modena
Country [69] 0 0
Italy
State/province [69] 0 0
Ravenna
Country [70] 0 0
Italy
State/province [70] 0 0
Roma
Country [71] 0 0
Italy
State/province [71] 0 0
San Giovanni Rotondo
Country [72] 0 0
Italy
State/province [72] 0 0
Terni
Country [73] 0 0
Italy
State/province [73] 0 0
Torino
Country [74] 0 0
New Zealand
State/province [74] 0 0
Auckland
Country [75] 0 0
New Zealand
State/province [75] 0 0
Aukland
Country [76] 0 0
New Zealand
State/province [76] 0 0
Manawatu-wanganui
Country [77] 0 0
New Zealand
State/province [77] 0 0
Christchurch
Country [78] 0 0
New Zealand
State/province [78] 0 0
Tauranga
Country [79] 0 0
Poland
State/province [79] 0 0
Dolnoslaskie
Country [80] 0 0
Poland
State/province [80] 0 0
Brzozów
Country [81] 0 0
Poland
State/province [81] 0 0
Chorzów
Country [82] 0 0
Poland
State/province [82] 0 0
Gdansk
Country [83] 0 0
Poland
State/province [83] 0 0
Gdynia
Country [84] 0 0
Poland
State/province [84] 0 0
Gliwice
Country [85] 0 0
Poland
State/province [85] 0 0
Kraków
Country [86] 0 0
Poland
State/province [86] 0 0
Lublin
Country [87] 0 0
Poland
State/province [87] 0 0
Lódz
Country [88] 0 0
Russian Federation
State/province [88] 0 0
Ekaterinburg
Country [89] 0 0
Russian Federation
State/province [89] 0 0
Kaluga
Country [90] 0 0
Russian Federation
State/province [90] 0 0
Kazan
Country [91] 0 0
Russian Federation
State/province [91] 0 0
Kemerovo
Country [92] 0 0
Russian Federation
State/province [92] 0 0
Moscow
Country [93] 0 0
Russian Federation
State/province [93] 0 0
Nizhny Novgorod
Country [94] 0 0
Russian Federation
State/province [94] 0 0
Penza
Country [95] 0 0
Russian Federation
State/province [95] 0 0
Perm
Country [96] 0 0
Russian Federation
State/province [96] 0 0
Ryazan
Country [97] 0 0
Russian Federation
State/province [97] 0 0
Saint Petersburg
Country [98] 0 0
Russian Federation
State/province [98] 0 0
Sochi
Country [99] 0 0
Russian Federation
State/province [99] 0 0
Tula
Country [100] 0 0
Russian Federation
State/province [100] 0 0
Volgograd
Country [101] 0 0
Russian Federation
State/province [101] 0 0
Yekaterinburg
Country [102] 0 0
Spain
State/province [102] 0 0
Barcelona
Country [103] 0 0
Spain
State/province [103] 0 0
Madrid
Country [104] 0 0
Spain
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Majadahonda
Country [105] 0 0
Spain
State/province [105] 0 0
Pamplona
Country [106] 0 0
Spain
State/province [106] 0 0
Valencia
Country [107] 0 0
Spain
State/province [107] 0 0
Zaragoza
Country [108] 0 0
Sweden
State/province [108] 0 0
Skane
Country [109] 0 0
Sweden
State/province [109] 0 0
Vastra Gotaland
Country [110] 0 0
Sweden
State/province [110] 0 0
Lulea
Country [111] 0 0
Sweden
State/province [111] 0 0
Orebro
Country [112] 0 0
Sweden
State/province [112] 0 0
Stockholm
Country [113] 0 0
Sweden
State/province [113] 0 0
Uppsala
Country [114] 0 0
Taiwan
State/province [114] 0 0
Hualien City
Country [115] 0 0
Taiwan
State/province [115] 0 0
New Taipei City
Country [116] 0 0
Taiwan
State/province [116] 0 0
Tainan City
Country [117] 0 0
Taiwan
State/province [117] 0 0
Taipei
Country [118] 0 0
United Kingdom
State/province [118] 0 0
England
Country [119] 0 0
United Kingdom
State/province [119] 0 0
Bournemouth
Country [120] 0 0
United Kingdom
State/province [120] 0 0
Leeds
Country [121] 0 0
United Kingdom
State/province [121] 0 0
London
Country [122] 0 0
United Kingdom
State/province [122] 0 0
Norwich
Country [123] 0 0
United Kingdom
State/province [123] 0 0
Nottingham
Country [124] 0 0
United Kingdom
State/province [124] 0 0
Plymouth
Country [125] 0 0
United Kingdom
State/province [125] 0 0
Southampton
Country [126] 0 0
United Kingdom
State/province [126] 0 0
Sunderland
Country [127] 0 0
United Kingdom
State/province [127] 0 0
Sutton
Country [128] 0 0
United Kingdom
State/province [128] 0 0
Wolverhampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
BeiGene
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03336333
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
BeiGene
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03336333