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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03734016




Registration number
NCT03734016
Ethics application status
Date submitted
2/11/2018
Date registered
7/11/2018

Titles & IDs
Public title
A Study of Zanubrutinib (BGB-3111) Versus Ibrutinib in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia
Scientific title
A Phase 3, Randomized Study of Zanubrutinib (BGB-3111) Compared With Ibrutinib in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Secondary ID [1] 0 0
2018-001366-42
Secondary ID [2] 0 0
BGB-3111-305
Universal Trial Number (UTN)
Trial acronym
ALPINE
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 - Ibrutinib

Experimental: Zanubrutinib - Participants received 160 mg zanubrutinib orally twice daily until disease progression, intolerable toxicity, initiation of alternative anticancer therapy, investigator/Sponsor decision, need for prohibited medication, study withdrawal, or pregnancy

Active comparator: Ibrutinib - Participants received Ibrutinib 420 mg orally once daily until disease progression, intolerable toxicity, initiation of alternative anticancer therapy, investigator/Sponsor decision, need for prohibited medication, study withdrawal, or pregnancy


Treatment: Drugs: Zanubrutinib
160 mg orally twice daily

Treatment: Drugs: Ibrutinib
Ibrutinib 420 mg orally once daily
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Response Rate (ORR) as Determined by Investigator Assessment
Timepoint [1] 0 0
Up to approximately 3 years and 9 months
Primary outcome [2] 0 0
ORR as Determined by Independent Review Committee (IRC)
Timepoint [2] 0 0
Up to approximately 3 years and 9 months
Secondary outcome [1] 0 0
Progression-free Survival Determined by Independent Central Review
Timepoint [1] 0 0
Up to 51 months
Secondary outcome [2] 0 0
Progression-free Survival Determined by Investigator Assessment
Timepoint [2] 0 0
Up to 51 months
Secondary outcome [3] 0 0
Duration of Response Determined by Investigator Assessment
Timepoint [3] 0 0
Up to 51 months
Secondary outcome [4] 0 0
Duration of Response Determined by Independent Central Review
Timepoint [4] 0 0
Up to 51 months
Secondary outcome [5] 0 0
Time to Treatment Failure
Timepoint [5] 0 0
Up to 51 months
Secondary outcome [6] 0 0
Overall Survival
Timepoint [6] 0 0
Up to 51 months
Secondary outcome [7] 0 0
Patient Reported Outcomes as Assessed by EORTC-QLQ-C30
Timepoint [7] 0 0
Up to 51 months
Secondary outcome [8] 0 0
Patient Reported Outcomes as Assessed by EQ-5D-5L
Timepoint [8] 0 0
Up to 51 months
Secondary outcome [9] 0 0
Incidence of Adverse Events as Assessed by CTCAE v4.03 [Safety and Tolerability]
Timepoint [9] 0 0
51 months
Secondary outcome [10] 0 0
Rate of Partial Response With Lymphocytosis (PR-L) or Higher Determined by Independent Central Review
Timepoint [10] 0 0
Up to 51 months
Secondary outcome [11] 0 0
Overall Response Rate Determined by Independent Central Review
Timepoint [11] 0 0
51 months

Eligibility
Key inclusion criteria
Key Inclusion Criteria

1. Confirmed diagnosis of CLL or SLL that meets the 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria
2. CLL/SLL requiring treatment per 2008 IWCLL criteria
3. Relapsed or refractory to at least 1 prior systemic therapy for CLL/SLL
4. Measurable disease by Computerized Tomography (CT)/magnetic resonance imaging (MRI)
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
6. Life expectancy = 6 months
7. Adequate bone marrow function
8. 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
Exclusion Criteria

1. Known prolymphocytic leukemia or history of, or currently suspected, Richter's transformation
2. Clinically significant cardiovascular disease.
3. 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 or breast
4. History of severe bleeding disorder or history of spontaneous bleeding requiring blood transfusion or other medical intervention
5. History of stroke or intracranial hemorrhage within 180 days before first dose of study drug
6. Severe or debilitating pulmonary disease
7. Active fungal, bacterial, and/or viral infection requiring systemic therapy
8. Known central nervous system involvement by leukemia or lymphoma
9. Known infection with HIV or active viral hepatitis B or C infection
10. Moderate or severe hepatic impairment, ie, Child-Pugh class B or C
11. Major surgery within 4 weeks of the first dose of study drug
12. Prior treatment with a (Burton's Kinase) BTK inhibitor
13. Toxicity from prior anticancer therapy that has not recovered to = Grade 1
14. Pregnant or lactating women
15. Vaccination with a live vaccine within 35 days prior to the first dose of study drug
16. Hypersensitivity to zanubrutinib, ibrutinib, or any of the other ingredients in either drug
17. Concurrent participation in another therapeutic clinical trial

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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/02/2024
Sample size
Target
Accrual to date
Final
652
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [3] 0 0
Icon Cancer Foundation - South Brisbane
Recruitment hospital [4] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [5] 0 0
Monash Health - Clayton
Recruitment hospital [6] 0 0
Peninsula Private Hospital - Frankston
Recruitment hospital [7] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2298 - Waratah
Recruitment postcode(s) [2] 0 0
4102 - Brisbane
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
3128 - Box Hill
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment postcode(s) [6] 0 0
3199 - Frankston
Recruitment postcode(s) [7] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Kansas
Country [7] 0 0
United States of America
State/province [7] 0 0
Kentucky
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Mississippi
Country [10] 0 0
United States of America
State/province [10] 0 0
Nebraska
Country [11] 0 0
United States of America
State/province [11] 0 0
Nevada
Country [12] 0 0
United States of America
State/province [12] 0 0
New Jersey
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
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Oregon
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United States of America
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Tennessee
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
United States of America
State/province [18] 0 0
Virginia
Country [19] 0 0
United States of America
State/province [19] 0 0
Washington
Country [20] 0 0
Belgium
State/province [20] 0 0
Wilrijk
Country [21] 0 0
China
State/province [21] 0 0
Beijing
Country [22] 0 0
China
State/province [22] 0 0
Fujian
Country [23] 0 0
China
State/province [23] 0 0
Guangdong
Country [24] 0 0
China
State/province [24] 0 0
Henan
Country [25] 0 0
China
State/province [25] 0 0
Hubei
Country [26] 0 0
China
State/province [26] 0 0
Jiangsu
Country [27] 0 0
China
State/province [27] 0 0
Jilin
Country [28] 0 0
China
State/province [28] 0 0
Liaoning
Country [29] 0 0
China
State/province [29] 0 0
Shanghai
Country [30] 0 0
China
State/province [30] 0 0
Sichuan
Country [31] 0 0
China
State/province [31] 0 0
Tianjin
Country [32] 0 0
China
State/province [32] 0 0
Zhejiang
Country [33] 0 0
Czechia
State/province [33] 0 0
Brno
Country [34] 0 0
Czechia
State/province [34] 0 0
Hradec Kralove
Country [35] 0 0
Czechia
State/province [35] 0 0
Olomouc
Country [36] 0 0
Czechia
State/province [36] 0 0
Ostrava
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France
State/province [37] 0 0
Cesson Sevigne
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France
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La Roche sur Yon
Country [39] 0 0
France
State/province [39] 0 0
Le Mans
Country [40] 0 0
France
State/province [40] 0 0
PierreBenite
Country [41] 0 0
France
State/province [41] 0 0
Poitiers
Country [42] 0 0
France
State/province [42] 0 0
Tours
Country [43] 0 0
Germany
State/province [43] 0 0
Hamm
Country [44] 0 0
Germany
State/province [44] 0 0
Koln
Country [45] 0 0
Italy
State/province [45] 0 0
Milano
Country [46] 0 0
Italy
State/province [46] 0 0
Roma
Country [47] 0 0
Italy
State/province [47] 0 0
Torino
Country [48] 0 0
Netherlands
State/province [48] 0 0
Apeldoorn
Country [49] 0 0
Netherlands
State/province [49] 0 0
Nijmegen
Country [50] 0 0
New Zealand
State/province [50] 0 0
Auckland
Country [51] 0 0
New Zealand
State/province [51] 0 0
Christchurch
Country [52] 0 0
New Zealand
State/province [52] 0 0
Hamilton Waikato
Country [53] 0 0
New Zealand
State/province [53] 0 0
Takapuna
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New Zealand
State/province [54] 0 0
Tauranga
Country [55] 0 0
New Zealand
State/province [55] 0 0
Wellington
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Poland
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Bialystok
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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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Poland
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Gdask
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Poland
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Krakow
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Poland
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Legnica
Country [63] 0 0
Poland
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Lodz
Country [64] 0 0
Poland
State/province [64] 0 0
Poznan
Country [65] 0 0
Spain
State/province [65] 0 0
Badalona
Country [66] 0 0
Spain
State/province [66] 0 0
Barcelona
Country [67] 0 0
Spain
State/province [67] 0 0
Girona
Country [68] 0 0
Spain
State/province [68] 0 0
Madrid
Country [69] 0 0
Spain
State/province [69] 0 0
Majadahonda
Country [70] 0 0
Spain
State/province [70] 0 0
Santander
Country [71] 0 0
Spain
State/province [71] 0 0
Toledo
Country [72] 0 0
Sweden
State/province [72] 0 0
Lund
Country [73] 0 0
Sweden
State/province [73] 0 0
Stockholm
Country [74] 0 0
Turkey
State/province [74] 0 0
Tekirdag
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Aberdeen
Country [76] 0 0
United Kingdom
State/province [76] 0 0
Birmingham
Country [77] 0 0
United Kingdom
State/province [77] 0 0
Bournemouth
Country [78] 0 0
United Kingdom
State/province [78] 0 0
Canterbury
Country [79] 0 0
United Kingdom
State/province [79] 0 0
Leeds
Country [80] 0 0
United Kingdom
State/province [80] 0 0
Norwich
Country [81] 0 0
United Kingdom
State/province [81] 0 0
Nottingham
Country [82] 0 0
United Kingdom
State/province [82] 0 0
Plymouth
Country [83] 0 0
United Kingdom
State/province [83] 0 0
Southampton
Country [84] 0 0
United Kingdom
State/province [84] 0 0
Sunderland

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

TypeCitations or Other Details
Journal Hillmen P, Brown JR, Eichhorst BF, Lamanna N, O'Br... [More Details]


Results are available at https://clinicaltrials.gov/study/NCT03734016