Back to resultsA Study of Zanubrutinib (BGB-3111) Versus Ibrutinib in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia (ALPINE)
Primary Purpose
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Status
Active
Phase
Phase 3
Locations
Poland
Study Type
Interventional
Intervention
Zanubrutinib
Ibrutinib
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Lymphocytic Leukemia focused on measuring Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, CLL, SLL, relapsed, refractory
Eligibility Criteria
Key Inclusion Criteria
- Confirmed diagnosis of CLL or SLL that meets the 2008 IWCLL criteria
- CLL/SLL requiring treatment per 2008 IWCLL criteria
- Relapsed or refractory to at least 1 prior systemic therapy for CLL/SLL
- Measurable disease by CT/magnetic resonance imaging (MRI)
- ECOG performance status of 0, 1, or 2
- Life expectancy ≥ 6 months
- Adequate bone marrow function
- Adequate renal and hepatic function
Key Exclusion Criteria
- Known prolymphocytic leukemia or history of, or currently 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 or breast
- History of severe bleeding disorder or history of spontaneous bleeding requiring blood transfusion or other medical intervention
- History of stroke or intracranial hemorrhage within 180 days before first dose of study drug
- Severe or debilitating pulmonary disease
- Active fungal, bacterial, and/or viral infection requiring systemic therapy
- Known central nervous system involvement by leukemia or lymphoma
- Known infection with HIV or active viral hepatitis B or C infection
- Moderate or severe hepatic impairment, ie, Child-Pugh class B or C
- Major surgery within 4 weeks of the first dose of study drug
- Prior treatment with a BTK inhibitor
- Toxicity from prior anticancer therapy that has not recovered to ≤ Grade 1
- Pregnant or lactating women
- Vaccination with a live vaccine within 35 days prior to the first dose of study drug
- Hypersensitivity to zanubrutinib, ibrutinib, or any of the other ingredients in either drug
- Concurrent participation in another therapeutic clinical trial
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Sites / Locations
- Interhem Opieka Szpitalna
- Szpital Specjalist W Brzozowie,Podkarpacki Osrodek Onkologiczny
- Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich
- Uniwersyteckie Centrum Kliniczne
- Copernicus Podmiot Leczniczy Sp Z Oo Wojewodzkie Centrum Onkologii
- Malopolskie Centrum Medyczne Sc
- Wojewodzki Szpital Specjalistyczny W Legnicy
- Wielospecjalistyczne Centrum Onkologii I Traumatologii Im M Kopernika W Lodzi
- Examen Sp Z Oo
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Zanubrutinib
Ibrutinib
Arm Description
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
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
Outcomes
Primary Outcome Measures
Overall Response Rate (ORR) as Determined by Investigator Assessment
ORR is percentage of participants with partial response (PR) or higher, (defined as Complete response/ Complete response with incomplete bone marrow recovery (CR/CRi) + PR + nodular PR) per investigator assessment using the "modified" 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines with modification for treatment-related lymphocytosis for participants with CLL and per Lugano Classification for non-Hodgkin lymphoma (NHL)) for participants with Small lymphocytic lymphoma (SLL)
ORR as Determined by Independent Review Committee (IRC)
ORR is the percentage of participants with PR or higher, (CR/CRi) + PR + nodular PR per IRC assessment using the "modified" 2008 IWCLL guidelines with modification for treatment-related lymphocytosis for participants with CLL and per Lugano Classification for NHL for participants with SLL
Secondary Outcome Measures
Progression-free Survival Determined by Independent Central Review
Progression-free Survival Determined by Investigator Assessment
Duration of Response Determined by Investigator Assessment
Duration of Response Determined by Independent Central Review
Time to Treatment Failure
Overall Survival
Patient Reported Outcomes as Assessed by EORTC-QLQ-C30
Patient Reported Outcomes as Assessed by EQ-5D-5L
Incidence of Adverse Events as Assessed by CTCAE v4.03 [Safety and Tolerability]
Rate of Partial Response With Lymphocytosis (PR-L) or Higher Determined by Independent Central Review
Proportion of participants who achieve a CR/CRi + PR + nodular PR + PR-L
Overall Response Rate Determined by Independent Central Review
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03734016
Brief Title
A Study of Zanubrutinib (BGB-3111) Versus Ibrutinib in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia
Acronym
ALPINE
Official 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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 1, 2018 (Actual)
Primary Completion Date
August 8, 2022 (Actual)
Study Completion Date
September 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BeiGene
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
Detailed Description
This is a global, Phase 3, randomized study of zanubrutinib versus ibrutinib in 652 participants with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma.
The primary efficacy endpoint is overall response rate determined by investigator assessment. Participants were randomized in a 1:1 manner to either zanubrutinib or ibrutinib. Treatment with zanubrutinib and ibrutinib was open label.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Keywords
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, CLL, SLL, relapsed, refractory
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
652 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Zanubrutinib
Arm Type
Experimental
Arm Description
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
Arm Title
Ibrutinib
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Zanubrutinib
Other Intervention Name(s)
BGB-3111, Brukinsa
Intervention Description
160 mg orally twice daily
Intervention Type
Drug
Intervention Name(s)
Ibrutinib
Other Intervention Name(s)
Imbruvica
Intervention Description
Ibrutinib 420 mg orally once daily
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR) as Determined by Investigator Assessment
Description
ORR is percentage of participants with partial response (PR) or higher, (defined as Complete response/ Complete response with incomplete bone marrow recovery (CR/CRi) + PR + nodular PR) per investigator assessment using the "modified" 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines with modification for treatment-related lymphocytosis for participants with CLL and per Lugano Classification for non-Hodgkin lymphoma (NHL)) for participants with Small lymphocytic lymphoma (SLL)
Time Frame
Up to approximately 3 years and 9 months
Title
ORR as Determined by Independent Review Committee (IRC)
Description
ORR is the percentage of participants with PR or higher, (CR/CRi) + PR + nodular PR per IRC assessment using the "modified" 2008 IWCLL guidelines with modification for treatment-related lymphocytosis for participants with CLL and per Lugano Classification for NHL for participants with SLL
Time Frame
Up to approximately 3 years and 9 months
Secondary Outcome Measure Information:
Title
Progression-free Survival Determined by Independent Central Review
Time Frame
Up to 51 months
Title
Progression-free Survival Determined by Investigator Assessment
Time Frame
Up to 51 months
Title
Duration of Response Determined by Investigator Assessment
Time Frame
Up to 51 months
Title
Duration of Response Determined by Independent Central Review
Time Frame
Up to 51 months
Title
Time to Treatment Failure
Time Frame
Up to 51 months
Title
Overall Survival
Time Frame
Up to 51 months
Title
Patient Reported Outcomes as Assessed by EORTC-QLQ-C30
Time Frame
Up to 51 months
Title
Patient Reported Outcomes as Assessed by EQ-5D-5L
Time Frame
Up to 51 months
Title
Incidence of Adverse Events as Assessed by CTCAE v4.03 [Safety and Tolerability]
Time Frame
51 months
Title
Rate of Partial Response With Lymphocytosis (PR-L) or Higher Determined by Independent Central Review
Description
Proportion of participants who achieve a CR/CRi + PR + nodular PR + PR-L
Time Frame
Up to 51 months
Title
Overall Response Rate Determined by Independent Central Review
Time Frame
51 months
Other Pre-specified Outcome Measures:
Title
Correlation Between Prognostic and Predictive Biomarkers and Clinical Outcomes
Time Frame
Up to 51 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria
Confirmed diagnosis of CLL or SLL that meets the 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria
CLL/SLL requiring treatment per 2008 IWCLL criteria
Relapsed or refractory to at least 1 prior systemic therapy for CLL/SLL
Measurable disease by Computerized Tomography (CT)/magnetic resonance imaging (MRI)
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 Exclusion Criteria
Known prolymphocytic leukemia or history of, or currently 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 or breast
History of severe bleeding disorder or history of spontaneous bleeding requiring blood transfusion or other medical intervention
History of stroke or intracranial hemorrhage within 180 days before first dose of study drug
Severe or debilitating pulmonary disease
Active fungal, bacterial, and/or viral infection requiring systemic therapy
Known central nervous system involvement by leukemia or lymphoma
Known infection with HIV or active viral hepatitis B or C infection
Moderate or severe hepatic impairment, ie, Child-Pugh class B or C
Major surgery within 4 weeks of the first dose of study drug
Prior treatment with a (Burton's Kinase) BTK inhibitor
Toxicity from prior anticancer therapy that has not recovered to ≤ Grade 1
Pregnant or lactating women
Vaccination with a live vaccine within 35 days prior to the first dose of study drug
Hypersensitivity to zanubrutinib, ibrutinib, or any of the other ingredients in either drug
Concurrent participation in another therapeutic clinical trial
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
BeiGene
Official's Role
Study Director
Facility Information:
Facility Name
Interhem Opieka Szpitalna
City
Bialystok
ZIP/Postal Code
15748
Country
Poland
Facility Name
Szpital Specjalist W Brzozowie,Podkarpacki Osrodek Onkologiczny
City
Brzozow
ZIP/Postal Code
36-200
Country
Poland
Facility Name
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich
City
Chorzow
ZIP/Postal Code
41-500
Country
Poland
Facility Name
Uniwersyteckie Centrum Kliniczne
City
Gdansk
ZIP/Postal Code
80-952
Country
Poland
Facility Name
Copernicus Podmiot Leczniczy Sp Z Oo Wojewodzkie Centrum Onkologii
City
Gdask
ZIP/Postal Code
80-219
Country
Poland
Facility Name
Malopolskie Centrum Medyczne Sc
City
Krakow
ZIP/Postal Code
30-510
Country
Poland
Facility Name
Wojewodzki Szpital Specjalistyczny W Legnicy
City
Legnica
ZIP/Postal Code
59-220
Country
Poland
Facility Name
Wielospecjalistyczne Centrum Onkologii I Traumatologii Im M Kopernika W Lodzi
City
Lodz
ZIP/Postal Code
93-510
Country
Poland
Facility Name
Examen Sp Z Oo
City
Poznan
ZIP/Postal Code
60-569
Country
Poland
12. IPD Sharing Statement
Plan to Share IPD
Yes
Citations:
PubMed Identifier
36511784
Citation
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.
Results Reference
background
PubMed Identifier
36395435
Citation
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.
Results Reference
background
PubMed Identifier
32207333
Citation
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.
Results Reference
result
Learn more about this trial
A Study of Zanubrutinib (BGB-3111) Versus Ibrutinib in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia
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