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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03336333
Ethics application status
Date submitted
1/11/2017
Date registered
8/11/2017

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
State/province [53] 0 0
Lyon
Country [54] 0 0
France
State/province [54] 0 0
Marseille
Country [55] 0 0
France
State/province [55] 0 0
Nantes
Country [56] 0 0
France
State/province [56] 0 0
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
State/province [104] 0 0
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
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?




Results publications and other study-related documents



Results are available at https://clinicaltrials.gov/study/NCT03336333