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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
Date last updated
26/10/2024

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
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United States of America
State/province [2] 0 0
California
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United States of America
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Colorado
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United States of America
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Florida
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United States of America
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Georgia
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United States of America
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Kansas
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Kentucky
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Massachusetts
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Mississippi
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Nebraska
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Nevada
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New Jersey
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New York
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North Carolina
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Oregon
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Tennessee
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Texas
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United States of America
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Virginia
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United States of America
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Washington
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Belgium
State/province [20] 0 0
Wilrijk
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China
State/province [21] 0 0
Beijing
Country [22] 0 0
China
State/province [22] 0 0
Fujian
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China
State/province [23] 0 0
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
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China
State/province [27] 0 0
Jilin
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China
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Liaoning
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China
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Shanghai
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China
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Sichuan
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China
State/province [31] 0 0
Tianjin
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China
State/province [32] 0 0
Zhejiang
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Czechia
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Brno
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Czechia
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Hradec Kralove
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Czechia
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Olomouc
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Czechia
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Ostrava
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France
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Cesson Sevigne
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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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PierreBenite
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France
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Poitiers
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France
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Tours
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Germany
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Hamm
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Germany
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Koln
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Italy
State/province [45] 0 0
Milano
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Italy
State/province [46] 0 0
Roma
Country [47] 0 0
Italy
State/province [47] 0 0
Torino
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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
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New Zealand
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Hamilton Waikato
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New Zealand
State/province [53] 0 0
Takapuna
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New Zealand
State/province [54] 0 0
Tauranga
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New Zealand
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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
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Poland
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Lodz
Country [64] 0 0
Poland
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Poznan
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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
State/province [67] 0 0
Girona
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Spain
State/province [68] 0 0
Madrid
Country [69] 0 0
Spain
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Majadahonda
Country [70] 0 0
Spain
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Santander
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Spain
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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
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United Kingdom
State/province [78] 0 0
Canterbury
Country [79] 0 0
United Kingdom
State/province [79] 0 0
Leeds
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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
This study is designed to compare the overall response rate of zanubrutinib versus ibrutinib in participants with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma.
Trial website
https://clinicaltrials.gov/study/NCT03734016
Trial related presentations / publications
Brown JR, Eichhorst B, Hillmen P, Jurczak W, Kazmierczak M, Lamanna N, O'Brien SM, Tam CS, Qiu L, Zhou K, Simkovic M, Mayer J, Gillespie-Twardy A, Ferrajoli A, Ganly PS, Weinkove R, Grosicki S, Mital A, Robak T, Osterborg A, Yimer HA, Salmi T, Wang MD, Fu L, Li J, Wu K, Cohen A, Shadman M. Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia. N Engl J Med. 2023 Jan 26;388(4):319-332. doi: 10.1056/NEJMoa2211582. Epub 2022 Dec 13.
Hillmen P, Eichhorst B, Brown JR, Lamanna N, O'Brien SM, Tam CS, Qiu L, Kazmierczak M, Zhou K, Simkovic M, Mayer J, Gillespie-Twardy A, Shadman M, Ferrajoli A, Ganly PS, Weinkove R, Grosicki S, Mital A, Robak T, Osterborg A, Yimer HA, Salmi T, Ji M, Yecies J, Idoine A, Wu K, Huang J, Jurczak W. Zanubrutinib Versus Ibrutinib in Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma: Interim Analysis of a Randomized Phase III Trial. J Clin Oncol. 2023 Feb 10;41(5):1035-1045. doi: 10.1200/JCO.22.00510. Epub 2022 Nov 17.
Hillmen P, Brown JR, Eichhorst BF, Lamanna N, O'Brien SM, Qiu L, Salmi T, Hilger J, Wu K, Cohen A, Huang J, Tam CS. ALPINE: zanubrutinib versus ibrutinib in relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma. Future Oncol. 2020 Apr;16(10):517-523. doi: 10.2217/fon-2019-0844. Epub 2020 Mar 24.
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/study/NCT03734016