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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 Repatriation General Hospital - Concord
Recruitment hospital [2] 0 0
The Tweed Valley Hospital - Cudgen
Recruitment hospital [3] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [4] 0 0
Westmead Hospital - Westmead
Recruitment hospital [5] 0 0
Icon Cancer Centre Wesley - Auchenflower
Recruitment hospital [6] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [7] 0 0
Royal Brisbane and Womens Hospital - Herston
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
Box Hill Hospital - Box Hill
Recruitment hospital [12] 0 0
Monash Health - Clayton
Recruitment hospital [13] 0 0
St Vincents Hospital Melbourne - Fitzroy
Recruitment hospital [14] 0 0
Peninsula Private Hospital - Frankston
Recruitment hospital [15] 0 0
Peter Maccallum Cancer Centre - Melbourne
Recruitment hospital [16] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
2487 - Cudgen
Recruitment postcode(s) [3] 0 0
2298 - Waratah
Recruitment postcode(s) [4] 0 0
2145 - Westmead
Recruitment postcode(s) [5] 0 0
4066 - Auchenflower
Recruitment postcode(s) [6] 0 0
4102 - Brisbane
Recruitment postcode(s) [7] 0 0
4029 - Herston
Recruitment postcode(s) [8] 0 0
5000 - Adelaide
Recruitment postcode(s) [9] 0 0
5011 - Woodville South
Recruitment postcode(s) [10] 0 0
7000 - Hobart
Recruitment postcode(s) [11] 0 0
3128 - Box Hill
Recruitment postcode(s) [12] 0 0
3168 - Clayton
Recruitment postcode(s) [13] 0 0
3065 - Fitzroy
Recruitment postcode(s) [14] 0 0
3199 - Frankston
Recruitment postcode(s) [15] 0 0
3000 - Melbourne
Recruitment postcode(s) [16] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Georgia
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Missouri
Country [5] 0 0
United States of America
State/province [5] 0 0
Nevada
Country [6] 0 0
United States of America
State/province [6] 0 0
New Jersey
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Oregon
Country [10] 0 0
United States of America
State/province [10] 0 0
South Dakota
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Virginia
Country [14] 0 0
United States of America
State/province [14] 0 0
Washington
Country [15] 0 0
Austria
State/province [15] 0 0
Innsbruck
Country [16] 0 0
Austria
State/province [16] 0 0
Linz
Country [17] 0 0
Austria
State/province [17] 0 0
Salzburg
Country [18] 0 0
Austria
State/province [18] 0 0
Wels
Country [19] 0 0
Belgium
State/province [19] 0 0
Brussels
Country [20] 0 0
Belgium
State/province [20] 0 0
Gent
Country [21] 0 0
Belgium
State/province [21] 0 0
Liege
Country [22] 0 0
Belgium
State/province [22] 0 0
Ottignies
Country [23] 0 0
Belgium
State/province [23] 0 0
Yvoir
Country [24] 0 0
China
State/province [24] 0 0
Anhui
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China
State/province [25] 0 0
Beijing
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China
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Chongqing
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China
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Fujian
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China
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Guangdong
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China
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Henan
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China
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Hubei
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China
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Jiangsu
Country [32] 0 0
China
State/province [32] 0 0
Jiangxi
Country [33] 0 0
China
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Jilin
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China
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Sichuan
Country [35] 0 0
China
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Tianjin
Country [36] 0 0
China
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Zhejiang
Country [37] 0 0
Czechia
State/province [37] 0 0
Brno
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Czechia
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Hradec Kralove
Country [39] 0 0
Czechia
State/province [39] 0 0
Olomouc
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Czechia
State/province [40] 0 0
Praha
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France
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Argenteuil cedex
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France
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Bordeaux
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France
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Caen cedex
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France
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La Roche sur Yon
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France
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Le Mans
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France
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Limoges Cedex
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France
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Marseille
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France
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Nantes Cedex
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France
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Paris
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France
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Pessac Cedex
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France
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PierreBenite
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Poitiers
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Reims Cedex
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Rennes Cedex
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Rouen Cedex
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Tours
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VandoeuvrelesNancy
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Italy
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Brescia
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Italy
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Meldola
Country [60] 0 0
Italy
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Milano
Country [61] 0 0
Italy
State/province [61] 0 0
Modena
Country [62] 0 0
Italy
State/province [62] 0 0
Ravenna
Country [63] 0 0
Italy
State/province [63] 0 0
Roma
Country [64] 0 0
Italy
State/province [64] 0 0
Terni
Country [65] 0 0
Italy
State/province [65] 0 0
Torino
Country [66] 0 0
New Zealand
State/province [66] 0 0
Auckland
Country [67] 0 0
New Zealand
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Christchurch
Country [68] 0 0
New Zealand
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Palmerston North
Country [69] 0 0
New Zealand
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Takapuna
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New Zealand
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Tauranga
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Poland
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Brzozow
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Poland
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Chorzow
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Poland
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Gdansk
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Gdynia
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Gliwice
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Poland
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Krakow
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Legnica
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Lodz
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Poland
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Lublin
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Russian Federation
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Kaluzhskaya Oblast'
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Russian Federation
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Krasnodarskiy Kray
Country [82] 0 0
Russian Federation
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Moskva
Country [83] 0 0
Russian Federation
State/province [83] 0 0
Nizhegorodskaya Oblast'
Country [84] 0 0
Russian Federation
State/province [84] 0 0
Penzenskaya Oblast'
Country [85] 0 0
Russian Federation
State/province [85] 0 0
Permskiy Kray
Country [86] 0 0
Russian Federation
State/province [86] 0 0
Pskovskaya Oblast'
Country [87] 0 0
Russian Federation
State/province [87] 0 0
Ryazanskaya Oblast'
Country [88] 0 0
Russian Federation
State/province [88] 0 0
Sankt-Peterburg
Country [89] 0 0
Russian Federation
State/province [89] 0 0
Sverdlovskaya Oblast'
Country [90] 0 0
Russian Federation
State/province [90] 0 0
Tambovskaya Oblast'
Country [91] 0 0
Russian Federation
State/province [91] 0 0
Tul'skaya Oblast'
Country [92] 0 0
Russian Federation
State/province [92] 0 0
Volgogradskaya Oblast'
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Spain
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Badalona
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Majadahonda
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Spain
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Pamplona
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Spain
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Valencia
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Spain
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Zaragoza
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Sweden
State/province [100] 0 0
Boras
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Sweden
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Goteborg
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Sweden
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Lund
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Sweden
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Orebro
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Sweden
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Stockholm
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Sweden
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Uppsala
Country [106] 0 0
Taiwan
State/province [106] 0 0
Hualien
Country [107] 0 0
Taiwan
State/province [107] 0 0
New Taipei City
Country [108] 0 0
Taiwan
State/province [108] 0 0
Taipei
Country [109] 0 0
United Kingdom
State/province [109] 0 0
Birmingham
Country [110] 0 0
United Kingdom
State/province [110] 0 0
Bournemouth
Country [111] 0 0
United Kingdom
State/province [111] 0 0
Cambridge
Country [112] 0 0
United Kingdom
State/province [112] 0 0
Canterbury
Country [113] 0 0
United Kingdom
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Greater Manchester
Country [114] 0 0
United Kingdom
State/province [114] 0 0
Leeds
Country [115] 0 0
United Kingdom
State/province [115] 0 0
London
Country [116] 0 0
United Kingdom
State/province [116] 0 0
Maidstone
Country [117] 0 0
United Kingdom
State/province [117] 0 0
Norwich
Country [118] 0 0
United Kingdom
State/province [118] 0 0
Nottingham
Country [119] 0 0
United Kingdom
State/province [119] 0 0
Plymouth
Country [120] 0 0
United Kingdom
State/province [120] 0 0
Southampton
Country [121] 0 0
United Kingdom
State/province [121] 0 0
Sunderland
Country [122] 0 0
United Kingdom
State/province [122] 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


What supporting documents are/will be available?




Results publications and other study-related documents



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