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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03336333
Ethics application status
Date submitted
1/11/2017
Date registered
8/11/2017
Date last updated
13/08/2020

Titles & IDs
Public title
A Study Comparing BGB-3111 With Bendamustine Plus Rituximab in Patients 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: Zanubrutinib (patients without del[17p]) - Approximately 225 subjects in Cohort 1 to receive zanubrutinib

Experimental: B+R - Approximately 225 subjects in Cohort 1 to receive bendamustine plus rituximab

Experimental: Zanubrutinib patients with del[17p]) - Approximately 100 subjects in Cohort 2 to receive zanubrutinib

Experimental: Zanubrutinib and venetoclax (patients with del[17p]) - Approximately 50 subjects in Cohort 3 to receive BGB-3111 and venetoclax


Treatment: Drugs: Zanubrutinib
Zanubrutinib will be administered as two 80-mg capsules by mouth twice a day (160 mg twice a day)

Treatment: Drugs: Bendamustine
Bendamustine will be administered intravenously at a dose of 90 mg/m2/day on the first 2 days of each cycle for 6 cycles. 1 cycle = 28 days.

Treatment: Drugs: Rituximab
Rituximab will be administered intravenously 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. 1 cycle = 28 days.

Treatment: Drugs: Venetoclax
Venetoclax will be administered by mouth once daily.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free survival between treatment groups in Cohort 1 (Zanubrutinib vs. B+R) as determined by independent central review (ICR).
Timepoint [1] 0 0
Up to 5 years.
Secondary outcome [1] 0 0
Overall response rate between treatment groups in Cohort 1
Timepoint [1] 0 0
Up to 5 years.
Secondary outcome [2] 0 0
Overall survival between treatment groups in Cohort 1.
Timepoint [2] 0 0
Up to 5 years.
Secondary outcome [3] 0 0
Duration of response between treatment groups in Cohort 1.
Timepoint [3] 0 0
Up to 5 years.
Secondary outcome [4] 0 0
Progression-free survival between treatment groups in Cohort 1 determined by investigator assessment (IA).
Timepoint [4] 0 0
Up to 5 years.
Secondary outcome [5] 0 0
Patient-reported outcomes in Cohort 1 measured by the EQ-5D-5L questionnaire.
Timepoint [5] 0 0
Up to 5 years.
Secondary outcome [6] 0 0
Overall response rate in Cohort 2.
Timepoint [6] 0 0
Up to 5 years.
Secondary outcome [7] 0 0
Progression-free survival in Cohort 2 as determined by ICR.
Timepoint [7] 0 0
Up to 5 years.
Secondary outcome [8] 0 0
Duration of response in Cohort 2 as determined by ICR.
Timepoint [8] 0 0
Up to 5 years.
Secondary outcome [9] 0 0
Overall response rate in Cohort 3.
Timepoint [9] 0 0
Up to 5 years.
Secondary outcome [10] 0 0
Progression-free survival in Cohort 3 as determined by ICR.
Timepoint [10] 0 0
Up to 5 years.
Secondary outcome [11] 0 0
Duration of response in Cohort 3 as determined by ICR.
Timepoint [11] 0 0
Up to 5 years.
Secondary outcome [12] 0 0
Rate of undetectable minimal residual disease in Cohort 3.
Timepoint [12] 0 0
Up to 5 years.
Secondary outcome [13] 0 0
Descriptive statistics will be used to summarize rate of adverse events.
Timepoint [13] 0 0
Up to 5 years.
Secondary outcome [14] 0 0
Plasma zanubrutinib concentrations will be summarized by scheduled time of collection.
Timepoint [14] 0 0
Up to 5 years.
Secondary outcome [15] 0 0
Patient-reported outcomes in Cohort 1 measured by the EORTC QLQ-C30 questionnaire.
Timepoint [15] 0 0
Up to 5 years.

Eligibility
Key inclusion criteria
All subjects

- Unsuitable for chemoimmunotherapy with FCR

- Confirmed diagnosis of CD20-positive CLL or SLL, requiring treatment.

- Measurable disease by imaging

- ECOG performance status of 0, 1 or 2.

- Life expectancy = 6 months.

- Adequate bone marrow function.

- Adequate renal and hepatic function.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
All subjects

- 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 CYP3A inhibitor or inducer.

- Concurrent participation in another therapeutic clinical trial.

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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
Czechia
State/province [28] 0 0
Brno
Country [29] 0 0
Czechia
State/province [29] 0 0
Hradec Králové
Country [30] 0 0
Czechia
State/province [30] 0 0
Olomouc
Country [31] 0 0
Czechia
State/province [31] 0 0
Ostrava-Poruba
Country [32] 0 0
Czechia
State/province [32] 0 0
Praha
Country [33] 0 0
France
State/province [33] 0 0
Poitou-charentes
Country [34] 0 0
France
State/province [34] 0 0
Argenteuil
Country [35] 0 0
France
State/province [35] 0 0
Bordeaux
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France
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Caen
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France
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La Roche sur Yon
Country [38] 0 0
France
State/province [38] 0 0
Le Mans
Country [39] 0 0
France
State/province [39] 0 0
Limoges
Country [40] 0 0
France
State/province [40] 0 0
Lyon
Country [41] 0 0
France
State/province [41] 0 0
Marseille
Country [42] 0 0
France
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Nantes
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France
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Paris
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France
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Pessac
Country [45] 0 0
France
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Pierre-Bénite
Country [46] 0 0
France
State/province [46] 0 0
Reims
Country [47] 0 0
France
State/province [47] 0 0
Rennes
Country [48] 0 0
France
State/province [48] 0 0
Rouen
Country [49] 0 0
France
State/province [49] 0 0
Tours
Country [50] 0 0
France
State/province [50] 0 0
Vandoeuvre-lès-Nancy
Country [51] 0 0
Italy
State/province [51] 0 0
Brescia
Country [52] 0 0
Italy
State/province [52] 0 0
Genova
Country [53] 0 0
Italy
State/province [53] 0 0
Meldola
Country [54] 0 0
Italy
State/province [54] 0 0
Milano
Country [55] 0 0
Italy
State/province [55] 0 0
Modena
Country [56] 0 0
Italy
State/province [56] 0 0
Ravenna
Country [57] 0 0
Italy
State/province [57] 0 0
Roma
Country [58] 0 0
Italy
State/province [58] 0 0
San Giovanni Rotondo
Country [59] 0 0
Italy
State/province [59] 0 0
Terni
Country [60] 0 0
Italy
State/province [60] 0 0
Torino
Country [61] 0 0
New Zealand
State/province [61] 0 0
Auckland
Country [62] 0 0
New Zealand
State/province [62] 0 0
Aukland
Country [63] 0 0
New Zealand
State/province [63] 0 0
Manawatu-wanganui
Country [64] 0 0
New Zealand
State/province [64] 0 0
Christchurch
Country [65] 0 0
New Zealand
State/province [65] 0 0
Tauranga
Country [66] 0 0
Poland
State/province [66] 0 0
Dolnoslaskie
Country [67] 0 0
Poland
State/province [67] 0 0
Brzozów
Country [68] 0 0
Poland
State/province [68] 0 0
Chorzów
Country [69] 0 0
Poland
State/province [69] 0 0
Gdansk
Country [70] 0 0
Poland
State/province [70] 0 0
Gdynia
Country [71] 0 0
Poland
State/province [71] 0 0
Gliwice
Country [72] 0 0
Poland
State/province [72] 0 0
Kraków
Country [73] 0 0
Poland
State/province [73] 0 0
Lublin
Country [74] 0 0
Poland
State/province [74] 0 0
Lódz
Country [75] 0 0
Russian Federation
State/province [75] 0 0
Ekaterinburg
Country [76] 0 0
Russian Federation
State/province [76] 0 0
Kaluga
Country [77] 0 0
Russian Federation
State/province [77] 0 0
Kazan
Country [78] 0 0
Russian Federation
State/province [78] 0 0
Kemerovo
Country [79] 0 0
Russian Federation
State/province [79] 0 0
Moscow
Country [80] 0 0
Russian Federation
State/province [80] 0 0
Nizhny Novgorod
Country [81] 0 0
Russian Federation
State/province [81] 0 0
Penza
Country [82] 0 0
Russian Federation
State/province [82] 0 0
Perm
Country [83] 0 0
Russian Federation
State/province [83] 0 0
Ryazan
Country [84] 0 0
Russian Federation
State/province [84] 0 0
Saint Petersburg
Country [85] 0 0
Russian Federation
State/province [85] 0 0
Sochi
Country [86] 0 0
Russian Federation
State/province [86] 0 0
Tula
Country [87] 0 0
Russian Federation
State/province [87] 0 0
Volgograd
Country [88] 0 0
Russian Federation
State/province [88] 0 0
Yekaterinburg
Country [89] 0 0
Spain
State/province [89] 0 0
Barcelona
Country [90] 0 0
Spain
State/province [90] 0 0
Madrid
Country [91] 0 0
Spain
State/province [91] 0 0
Majadahonda
Country [92] 0 0
Spain
State/province [92] 0 0
Pamplona
Country [93] 0 0
Spain
State/province [93] 0 0
Valencia
Country [94] 0 0
Spain
State/province [94] 0 0
Zaragoza
Country [95] 0 0
Sweden
State/province [95] 0 0
Skane
Country [96] 0 0
Sweden
State/province [96] 0 0
Vastra Gotaland
Country [97] 0 0
Sweden
State/province [97] 0 0
Lulea
Country [98] 0 0
Sweden
State/province [98] 0 0
Orebro
Country [99] 0 0
Sweden
State/province [99] 0 0
Stockholm
Country [100] 0 0
Sweden
State/province [100] 0 0
Uppsala
Country [101] 0 0
Taiwan
State/province [101] 0 0
Hualien City
Country [102] 0 0
Taiwan
State/province [102] 0 0
New Taipei City
Country [103] 0 0
Taiwan
State/province [103] 0 0
Tainan City
Country [104] 0 0
Taiwan
State/province [104] 0 0
Taipei
Country [105] 0 0
United Kingdom
State/province [105] 0 0
England
Country [106] 0 0
United Kingdom
State/province [106] 0 0
Bournemouth
Country [107] 0 0
United Kingdom
State/province [107] 0 0
Leeds
Country [108] 0 0
United Kingdom
State/province [108] 0 0
London
Country [109] 0 0
United Kingdom
State/province [109] 0 0
Norwich
Country [110] 0 0
United Kingdom
State/province [110] 0 0
Nottingham
Country [111] 0 0
United Kingdom
State/province [111] 0 0
Plymouth
Country [112] 0 0
United Kingdom
State/province [112] 0 0
Southampton
Country [113] 0 0
United Kingdom
State/province [113] 0 0
Sunderland
Country [114] 0 0
United Kingdom
State/province [114] 0 0
Sutton
Country [115] 0 0
United Kingdom
State/province [115] 0 0
Wolverhampton

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

Ethics approval
Ethics application status

Summary
Brief summary
This study will enroll subjects with previously untreated CLL/SLL into three cohorts (Cohort
1 without del[17p] and Cohorts 2 and 3 with del[17p]). Cohort 1 subjects will receive either
zanubrutinib alone or "bendamustine (B) and rituximab (R)". Cohort 2 subjects will receive
zanubrutinib alone. Once Cohort 2 has finished enrollment, Cohort 3 will be opened in
selected countries/sites where patients will receive zanubrutinib and venetoclax. The primary
purpose is to evaluate the efficacy and safety of zanubrutinib versus bendamustine and
rituximab in Cohort 1.
Trial website
https://clinicaltrials.gov/show/NCT03336333
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jason Paik, MD
Address 0 0
BeiGene
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
BeiGene
Address 0 0
Country 0 0
Phone 0 0
+1-877-828-5568
Fax 0 0
Email 0 0
clinicaltrials@beigene.com
Contact person for scientific queries

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