The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03734016
Ethics application status
Date submitted
2/11/2018
Date registered
7/11/2018
Date last updated
9/08/2019

Titles & IDs
Public title
A Study of Zanubrutinib (BGB-3111) Versus Ibrutinib in Patients 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 - BGB-3111
Treatment: Drugs - Ibrutinib

Experimental: Zanubrutinib - Zanubrutinib (BGB-3111) will be orally administered until disease progression or unacceptable toxicity.

Active Comparator: Ibrutinib - Ibrutinib will be orally administered until disease progression or unacceptable toxicity.


Treatment: Drugs: BGB-3111
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 determined by independent central review
Timepoint [1] 0 0
29 months
Secondary outcome [1] 0 0
Progression-free survival determined by independent central review
Timepoint [1] 0 0
65 months
Secondary outcome [2] 0 0
Progression-free survival determined by investigator assessment
Timepoint [2] 0 0
65 months
Secondary outcome [3] 0 0
Duration of response determined by independent central review
Timepoint [3] 0 0
65 months
Secondary outcome [4] 0 0
Duration of response determined by investigator assessment
Timepoint [4] 0 0
65 months
Secondary outcome [5] 0 0
Time to treatment failure
Timepoint [5] 0 0
65 months
Secondary outcome [6] 0 0
Overall survival
Timepoint [6] 0 0
65 months
Secondary outcome [7] 0 0
Patient reported outcomes as assessed by EORTC-QLQ-C30
Timepoint [7] 0 0
65 months
Secondary outcome [8] 0 0
Patient reported outcomes as assessed by EQ-5D-5L
Timepoint [8] 0 0
65 months
Secondary outcome [9] 0 0
Incidence of adverse events as assessed by CTCAE v4.03 [Safety and Tolerability]
Timepoint [9] 0 0
80 months

Eligibility
Key inclusion criteria
Inclusion Criteria

1. Age 18 years or older

2. Confirmed diagnosis of CLL or SLL that meets the 2008 IWCLL criteria

3. CLL/SLL requiring treatment per 2008 IWCLL criteria

4. Relapsed or refractory to at least 1 prior systemic therapy for CLL/SLL

5. Measurable disease by CT/magnetic resonance imaging (MRI)

6. ECOG performance status of 0, 1, or 2

7. Life expectancy = 6 months

8. Adequate bone marrow function

9. 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
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, superficial bladder cancer, or 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 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

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,VictoraVIC
Recruitment hospital [1] 0 0
Calvary Mater Newcastle - Newcastle
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [3] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [4] 0 0
St Vincents Hospital Melbourne - Fitzroy
Recruitment hospital [5] 0 0
Monash Health, Monash Medical Centre - Clayton
Recruitment hospital [6] 0 0
Peninsula Private Hospital - Frankston
Recruitment hospital [7] 0 0
Ashford Cancer Centre Research - Kurralta Park
Recruitment hospital [8] 0 0
Icon Cancer Foundation - Milton
Recruitment hospital [9] 0 0
Border Medical Oncology - Wodonga
Recruitment postcode(s) [1] 0 0
- Newcastle
Recruitment postcode(s) [2] 0 0
- Woolloongabba
Recruitment postcode(s) [3] 0 0
- Box Hill
Recruitment postcode(s) [4] 0 0
- Fitzroy
Recruitment postcode(s) [5] 0 0
- Clayton
Recruitment postcode(s) [6] 0 0
3199 - Frankston
Recruitment postcode(s) [7] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [8] 0 0
4066 - Milton
Recruitment postcode(s) [9] 0 0
- Wodonga
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
Illinois
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
Missouri
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
State/province [15] 0 0
Oregon
Country [16] 0 0
United States of America
State/province [16] 0 0
South Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Tennessee
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Virginia
Country [20] 0 0
United States of America
State/province [20] 0 0
Washington
Country [21] 0 0
Belgium
State/province [21] 0 0
Namur
Country [22] 0 0
Belgium
State/province [22] 0 0
Wilrijk
Country [23] 0 0
China
State/province [23] 0 0
Anhui
Country [24] 0 0
China
State/province [24] 0 0
Beijing
Country [25] 0 0
China
State/province [25] 0 0
Fujian
Country [26] 0 0
China
State/province [26] 0 0
Guangdong
Country [27] 0 0
China
State/province [27] 0 0
Henan
Country [28] 0 0
China
State/province [28] 0 0
Hubei
Country [29] 0 0
China
State/province [29] 0 0
Jiangsu
Country [30] 0 0
China
State/province [30] 0 0
Jiangxi
Country [31] 0 0
China
State/province [31] 0 0
Jilin
Country [32] 0 0
China
State/province [32] 0 0
Liaoning
Country [33] 0 0
China
State/province [33] 0 0
Shanghai
Country [34] 0 0
China
State/province [34] 0 0
Sichuan
Country [35] 0 0
China
State/province [35] 0 0
Tianjin
Country [36] 0 0
China
State/province [36] 0 0
Zhejiang
Country [37] 0 0
Czechia
State/province [37] 0 0
Jihomoravský Kraj
Country [38] 0 0
Czechia
State/province [38] 0 0
Hradec Králové
Country [39] 0 0
Czechia
State/province [39] 0 0
Olomouc
Country [40] 0 0
Czechia
State/province [40] 0 0
Ostrava
Country [41] 0 0
France
State/province [41] 0 0
Cesson-Sévigné
Country [42] 0 0
France
State/province [42] 0 0
La Roche-sur-Yon
Country [43] 0 0
France
State/province [43] 0 0
Le Mans
Country [44] 0 0
France
State/province [44] 0 0
Pierre Benite
Country [45] 0 0
France
State/province [45] 0 0
Poitiers
Country [46] 0 0
France
State/province [46] 0 0
Rennes
Country [47] 0 0
France
State/province [47] 0 0
Tours
Country [48] 0 0
Italy
State/province [48] 0 0
Emilia-Romagna
Country [49] 0 0
Italy
State/province [49] 0 0
Lazio
Country [50] 0 0
Italy
State/province [50] 0 0
Milano
Country [51] 0 0
Italy
State/province [51] 0 0
San Giovanni Rotondo
Country [52] 0 0
Netherlands
State/province [52] 0 0
Zuid-Holland
Country [53] 0 0
Netherlands
State/province [53] 0 0
Apeldoorn
Country [54] 0 0
Netherlands
State/province [54] 0 0
Groningen
Country [55] 0 0
New Zealand
State/province [55] 0 0
Auckland
Country [56] 0 0
New Zealand
State/province [56] 0 0
South Island
Country [57] 0 0
New Zealand
State/province [57] 0 0
Hamilton
Country [58] 0 0
New Zealand
State/province [58] 0 0
Newtown
Country [59] 0 0
New Zealand
State/province [59] 0 0
Tauranga
Country [60] 0 0
Poland
State/province [60] 0 0
Dolnoslaskie
Country [61] 0 0
Poland
State/province [61] 0 0
JPodkarpackie
Country [62] 0 0
Poland
State/province [62] 0 0
Lódzkie
Country [63] 0 0
Poland
State/province [63] 0 0
Slaskie
Country [64] 0 0
Poland
State/province [64] 0 0
Bialystok
Country [65] 0 0
Poland
State/province [65] 0 0
Gdansk
Country [66] 0 0
Poland
State/province [66] 0 0
Kraków
Country [67] 0 0
Poland
State/province [67] 0 0
Opole
Country [68] 0 0
Poland
State/province [68] 0 0
Skorzewo
Country [69] 0 0
Spain
State/province [69] 0 0
Asturias
Country [70] 0 0
Spain
State/province [70] 0 0
Cantabria
Country [71] 0 0
Spain
State/province [71] 0 0
Madried
Country [72] 0 0
Spain
State/province [72] 0 0
Navarra
Country [73] 0 0
Spain
State/province [73] 0 0
Barcelona
Country [74] 0 0
Spain
State/province [74] 0 0
Girona
Country [75] 0 0
Spain
State/province [75] 0 0
Madrid
Country [76] 0 0
Spain
State/province [76] 0 0
Majadahonda
Country [77] 0 0
Spain
State/province [77] 0 0
Toledo
Country [78] 0 0
Turkey
State/province [78] 0 0
Ankara
Country [79] 0 0
Turkey
State/province [79] 0 0
Kayseri
Country [80] 0 0
Turkey
State/province [80] 0 0
Mersin
Country [81] 0 0
Turkey
State/province [81] 0 0
Tekirdag
Country [82] 0 0
United Kingdom
State/province [82] 0 0
Aberdeen City
Country [83] 0 0
United Kingdom
State/province [83] 0 0
Glasgow City
Country [84] 0 0
United Kingdom
State/province [84] 0 0
Norfolk
Country [85] 0 0
United Kingdom
State/province [85] 0 0
Northumberland
Country [86] 0 0
United Kingdom
State/province [86] 0 0
Oxfordshire
Country [87] 0 0
United Kingdom
State/province [87] 0 0
Birmingham
Country [88] 0 0
United Kingdom
State/province [88] 0 0
Canterbury
Country [89] 0 0
United Kingdom
State/province [89] 0 0
Leeds
Country [90] 0 0
United Kingdom
State/province [90] 0 0
London
Country [91] 0 0
United Kingdom
State/province [91] 0 0
Manchester
Country [92] 0 0
United Kingdom
State/province [92] 0 0
Nottingham
Country [93] 0 0
United Kingdom
State/province [93] 0 0
Plymouth
Country [94] 0 0
United Kingdom
State/province [94] 0 0
Southampton

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 patients with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic
lymphoma.
Trial website
https://clinicaltrials.gov/show/NCT03734016
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Tommi Salmi, MD
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/NCT03734016