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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03734016




Registration number
NCT03734016
Ethics application status
Date submitted
2/11/2018
Date registered
7/11/2018
Date last updated
8/11/2023

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
Active, not recruiting
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
30/04/2024
Actual
Sample size
Target
Accrual to date
Final
652
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Poland
State/province [1] 0 0
Bialystok
Country [2] 0 0
Poland
State/province [2] 0 0
Brzozow
Country [3] 0 0
Poland
State/province [3] 0 0
Chorzow
Country [4] 0 0
Poland
State/province [4] 0 0
Gdansk
Country [5] 0 0
Poland
State/province [5] 0 0
Gdask
Country [6] 0 0
Poland
State/province [6] 0 0
Krakow
Country [7] 0 0
Poland
State/province [7] 0 0
Legnica
Country [8] 0 0
Poland
State/province [8] 0 0
Lodz
Country [9] 0 0
Poland
State/province [9] 0 0
Poznan

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/ct2/show/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.
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

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/ct2/show/NCT03734016