A Study of Zanubrutinib (BGB-3111) Versus Ibrutinib in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia

Chronic Lymphocytic Leukemia Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03734016
• Other study ID #: BGB-3111-305
• Secondary ID: 2018-001366-42CT
• Status: Completed
• Phase: Phase 3
• Start date: November 1, 2018
• Est. completion date: February 28, 2024

Study information

• Verified date: March 2024
• Source: BeiGene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 652
• Est. completion date: February 28, 2024
• Est. primary completion date: August 8, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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.

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Small Lymphocytic Lymphoma

Intervention

Drug:
• Zanubrutinib
160 mg orally twice daily
• Ibrutinib
Ibrutinib 420 mg orally once daily

Locations

Country	Name	City	State
Poland	Interhem Opieka Szpitalna	Bialystok
Poland	Szpital Specjalist W Brzozowie,Podkarpacki Osrodek Onkologiczny	Brzozow
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich	Chorzow
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Copernicus Podmiot Leczniczy Sp Z Oo Wojewodzkie Centrum Onkologii	Gdask
Poland	Malopolskie Centrum Medyczne Sc	Krakow
Poland	Wojewodzki Szpital Specjalistyczny W Legnicy	Legnica
Poland	Wielospecjalistyczne Centrum Onkologii I Traumatologii Im M Kopernika W Lodzi	Lodz
Poland	Examen Sp Z Oo	Poznan

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Country where clinical trial is conducted

Poland, 

References & Publications (3)

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. — View 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 Ap — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Correlation Between Prognostic and Predictive Biomarkers and Clinical Outcomes		Up to 51 months
Primary	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)	Up to approximately 3 years and 9 months
Primary	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	Up to approximately 3 years and 9 months
Secondary	Progression-free Survival Determined by Independent Central Review		Up to 51 months
Secondary	Progression-free Survival Determined by Investigator Assessment		Up to 51 months
Secondary	Duration of Response Determined by Investigator Assessment		Up to 51 months
Secondary	Duration of Response Determined by Independent Central Review		Up to 51 months
Secondary	Time to Treatment Failure		Up to 51 months
Secondary	Overall Survival		Up to 51 months
Secondary	Patient Reported Outcomes as Assessed by EORTC-QLQ-C30		Up to 51 months
Secondary	Patient Reported Outcomes as Assessed by EQ-5D-5L		Up to 51 months
Secondary	Incidence of Adverse Events as Assessed by CTCAE v4.03 [Safety and Tolerability]		51 months
Secondary	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	Up to 51 months
Secondary	Overall Response Rate Determined by Independent Central Review		51 months