ALPINE: A Study of Zanubrutinib (BGB-3111) Versus Ibrutinib in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia
Study Details
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 3 |
Detailed Description
This is a global, Phase 3, randomized study of zanubrutinib versus ibrutinib in approximately 600 participants with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma.
The primary efficacy endpoint is overall response rate determined by investigator assessment. Participants will be randomized in a 1:1 manner to either zanubrutinib or ibrutinib. Treatment with zanubrutinib and ibrutinib will be open label.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Zanubrutinib Zanubrutinib will be orally administered until disease progression or unacceptable toxicity. |
Drug: Zanubrutinib
160 mg orally twice daily
Other Names:
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Active Comparator: Ibrutinib Ibrutinib will be orally administered until disease progression or unacceptable toxicity. |
Drug: Ibrutinib
Ibrutinib 420 mg orally once daily
Other Names:
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Outcome Measures
Primary Outcome Measures
- Overall response rate determined by investigator assessment [Up to 50 months]
Secondary Outcome Measures
- Progression-free survival determined by independent central review [Up to 50 months]
- Progression-free survival determined by investigator assessment [Up to 51 months]
- Duration of response determined by investigator assessment [Up to 51 months]
- Duration of response determined by independent central review [Up to 51 months]
- Time to treatment failure [Up to 51 months]
- Overall survival [Up to 51 months]
- Patient reported outcomes as assessed by EORTC-QLQ-C30 [Up to 51 months]
- Patient reported outcomes as assessed by EQ-5D-5L [Up to 51 months]
- Incidence of adverse events as assessed by CTCAE v4.03 [Safety and Tolerability] [51 months]
- Rate of partial response with lymphocytosis (PR-L) or higher determined by independent central review [Up to 51 months]
Proportion of participants who achieve a CR/CRi + PR + nodular PR + PR-L
- Overall response rate determined by independent central review [51 months]
Other Outcome Measures
- Correlation between prognostic and predictive biomarkers and clinical outcomes [Up to 51 months]
Eligibility Criteria
Criteria
Key Inclusion Criteria
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Confirmed diagnosis of CLL or SLL that meets the 2008 IWCLL criteria
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CLL/SLL requiring treatment per 2008 IWCLL criteria
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Relapsed or refractory to at least 1 prior systemic therapy for CLL/SLL
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Measurable disease by CT/magnetic resonance imaging (MRI)
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ECOG performance status of 0, 1, or 2
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Life expectancy ≥ 6 months
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Adequate bone marrow function
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Adequate renal and hepatic function
Key Exclusion Criteria
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Known prolymphocytic leukemia or history of, or currently suspected, Richter's transformation
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Clinically significant cardiovascular disease.
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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
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History of severe bleeding disorder or history of spontaneous bleeding requiring blood transfusion or other medical intervention
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History of stroke or intracranial hemorrhage within 180 days before first dose of study drug
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Severe or debilitating pulmonary disease
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Active fungal, bacterial, and/or viral infection requiring systemic therapy
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Known central nervous system involvement by leukemia or lymphoma
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Known infection with HIV or active viral hepatitis B or C infection
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Moderate or severe hepatic impairment, ie, Child-Pugh class B or C
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Major surgery within 4 weeks of the first dose of study drug
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Prior treatment with a BTK inhibitor
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Toxicity from prior anticancer therapy that has not recovered to ≤ Grade 1
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Pregnant or lactating women
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Vaccination with a live vaccine within 35 days prior to the first dose of study drug
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Hypersensitivity to zanubrutinib, ibrutinib, or any of the other ingredients in either drug
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Concurrent participation in another therapeutic clinical trial
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | CARTI Cancer Center | Little Rock | Arkansas | United States | 72205 |
2 | David Geffen School of Medicine at UCLA | Los Angeles | California | United States | 90095 |
3 | University of California Irvine Medical Center | Orange | California | United States | 92868 |
4 | Rocky Mountain Cancer Centers (Aurora) - USOR | Aurora | Colorado | United States | 80012 |
5 | SCRI Florida Cancer Specialists South | Fort Myers | Florida | United States | 33909 |
6 | SCRI Florida Cancer Specialists North | Saint Petersburg | Florida | United States | 33705 |
7 | Augusta University | Augusta | Georgia | United States | 30912 |
8 | Illinois Cancer Specialists (Niles) - USOR | Niles | Illinois | United States | 60714 |
9 | Norton Cancer Institute - Pavilion | Louisville | Kentucky | United States | 40202 |
10 | Dana Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
11 | Hattiesburg Hematology and Oncology Clinic | Hattiesburg | Mississippi | United States | 39401 |
12 | Central Care Cancer Center | Bolivar | Missouri | United States | 65613 |
13 | SCRI HCA Midwest Health | Kansas City | Missouri | United States | 66211 |
14 | University of Nebraska Medical Center | Omaha | Nebraska | United States | 68198 |
15 | Comprehensive Cancer Centers of Nevada - USOR | Las Vegas | Nevada | United States | 89169 |
16 | New Jersey Hematology Oncology Associates LLC | Brick | New Jersey | United States | 08724 |
17 | Summit Medical Group | Florham Park | New Jersey | United States | 07932 |
18 | Atlantic Health System | Morristown | New Jersey | United States | 07960 |
19 | Clinical Research Alliance Inc | Lake Success | New York | United States | 11042 |
20 | Columbia University Medical Center | New York | New York | United States | 10032 |
21 | Duke University Medical Center | Durham | North Carolina | United States | 27705 |
22 | Leo W. Jenkins Cancer Center | Greenville | North Carolina | United States | 27834 |
23 | Ohio State University Comprehensive Cancer Center | Columbus | Ohio | United States | 43210 |
24 | Willamette Valley Cancer Center | Eugene | Oregon | United States | 97401 |
25 | Oregon Health and Science University | Portland | Oregon | United States | 97239 |
26 | Greenville Health System Cancer Institute | Greenville | South Carolina | United States | 29601 |
27 | SCRI Tennessee Oncology Chattanooga | Chattanooga | Tennessee | United States | 37404 |
28 | SCRI Tennessee Oncology Nashville | Nashville | Tennessee | United States | 37211 |
29 | Texas Oncology (West 38) - USOR | Austin | Texas | United States | 78705 |
30 | Texas Oncology (LOOP) - USOR | Dallas | Texas | United States | 75230 |
31 | Texas Oncology (Walnut) - USOR | Dallas | Texas | United States | 75231 |
32 | Texas Oncology-Baylor Charles A. Sammons Cancer Center | Dallas | Texas | United States | 75246 |
33 | Texas Oncology-Fort Worth Cancer Center | Fort Worth | Texas | United States | 76104 |
34 | MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
35 | Joe Arrington Cancer Research and Treatment Center | Lubbock | Texas | United States | 79410 |
36 | Texas Oncology - San Antonio Medical Center - USOR | San Antonio | Texas | United States | 78240 |
37 | Texas Oncology (Tyler) - USOR | Tyler | Texas | United States | 75702 |
38 | Oncology and Hematology Associates of Southwest Virginia, Inc | Roanoke | Virginia | United States | 24014 |
39 | VA Puget Sound Health Care System - NAVREF | Seattle | Washington | United States | 98108 |
40 | Fred Hutchinson Cancer Research Center | Seattle | Washington | United States | 98109 |
41 | Medical Oncology Associates | Spokane | Washington | United States | 99208 |
42 | Calvary Mater Newcastle | Newcastle | New South Wales | Australia | |
43 | Princess Alexandra Hospital | Woolloongabba | Queensland | Australia | |
44 | Box Hill Hospital | Box Hill | Victora | Australia | |
45 | St Vincents Hospital Melbourne | Fitzroy | Victoria | Australia | |
46 | Royal Perth Hospital | Perth | Western Australia | Australia | 6000 |
47 | Monash Health, Monash Medical Centre | Clayton | Australia | ||
48 | Peninsula Private Hospital | Frankston | Australia | 3199 | |
49 | Ashford Cancer Centre Research | Kurralta Park | Australia | 5037 | |
50 | Icon Cancer Foundation | Milton | Australia | 4066 | |
51 | Border Medical Oncology | Wodonga | Australia | ||
52 | UZ Brussel | Brussel | Brussels | Belgium | 1090 |
53 | CHU UCL Namur asbl - Site Godinne | Yvoir | Namur | Belgium | |
54 | GasthuisZusters Antwerpen | Wilrijk | Belgium | ||
55 | Anhui Province Hospital | Hefei | Anhui | China | 230001 |
56 | Peking university Third Hospital | Beijing | Beijing | China | 100191 |
57 | Peking Union Medical College Hospital | Beijing | Beijing | China | 100730 |
58 | Fujian Medical University Union Hospital | Fuzhou | Fujian | China | 350001 |
59 | Quanzhou First Hospital of Fujian Province | Quanzhou | Fujian | China | 362002 |
60 | Guangdong General Hospital | Guangzhou | Guangdong | China | |
61 | Nanfang Hospital | Guanzhou | Guangdong | China | 510515 |
62 | Henan Cancer Hospital | Zhengzhou | Henan | China | 450008 |
63 | Wuhan Union Hospital | Wuhan | Hubei | China | 430022 |
64 | Jiangsu Province Hospital | Nanjing | Jiangsu | China | 210029 |
65 | The affiliated Hospital of Xuzhou Medical university | Xuzhou | Jiangsu | China | 221006 |
66 | The First affiliated hospital of Nanchang University | Nanchang | Jiangxi | China | |
67 | The First Hospital of Jilin University | Changchun | Jilin | China | 130021 |
68 | Shengjing Hospital of China Medical University | Shenyang | Liaoning | China | 110022 |
69 | Tongji Hospital of Tongji University | Shanghai | Shanghai | China | 200092 |
70 | West China Hospital ,Sichuan University | Chengdu | Sichuan | China | 610041 |
71 | Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences | Tianjin | Tianjin | China | 300020 |
72 | The First Hospital of Zhejiang Province | Hangzhou | Zhejiang | China | 310003 |
73 | The first affiliated hospital of Wenzhou Medical University | Wenzhou | Zhejiang | China | 325000 |
74 | Beijing Friendship Hospital-Capital Medical University | Beijing | China | 100050 | |
75 | Zhongshan hospital of Fudan University | Shanghai | China | 200032 | |
76 | Tianjin Medical University Cancer Institute and Hospital | Tianjin | China | 300060 | |
77 | Fakultni nemocnice Brno | Brno | Jihomoravský Kraj | Czechia | |
78 | Fakultni nemocnice Hradec Kralove | Hradec Králové | Czechia | ||
79 | Fakultni nemocnice Olomouc | Olomouc | Czechia | ||
80 | Fakultni nemocnice Ostrava | Ostrava | Czechia | ||
81 | Hopital Prive Sevigne | Cesson-Sévigné | France | ||
82 | Centre Hospitalier Departemental de Vendee | La Roche-sur-Yon | France | ||
83 | Centre Hospitalier Le Mans | Le Mans | France | ||
84 | Centre Hospitalier Lyon Sud | Pierre Benite | France | 69495 | |
85 | CHRU de Poitiers La Miletrie | Poitiers | France | ||
86 | CHRU Bretonneau | Tours | France | ||
87 | Onkologische Schwerpunktpraxis Bielefeld | Bielefeld | Nordrhein-Westfalen | Germany | 33604 |
88 | Evangelisches Krankenhaus Hamm | Hamm | Nordrhein-Westfalen | Germany | 59063 |
89 | Uniklinik Köln | Köln | Nordrhein-Westfalen | Germany | 50937 |
90 | Gemeinschaftspraxis fur Hamatologie und Onkologie | Münster | Nordrhein-Westfalen | Germany | 48149 |
91 | Onkoligische Gemeinschaftspraxis Dres. Dörfel/Göhler | Dresden | Germany | 1127 | |
92 | Fondazione Policlinico Universitario A Gemelli | Roma | Lazio | Italy | |
93 | Ospedale San Raffaele S.r.l. - PPDS | Milan | Milano | Italy | |
94 | ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda Ca' Granda | Milano | Italy | ||
95 | Azienda Ospedaliera Città della Salute e della Scienza di Torino | Torino | Italy | 10126 | |
96 | Albert Schweitzer Ziekenhuis | Dordrecht | Zuid-Holland | Netherlands | |
97 | Gelre Ziekenhuizen | Apeldoorn | Netherlands | ||
98 | Martini Ziekenhuis | Groningen | Netherlands | ||
99 | North Shore Hospital | Takapuna | Auckland | New Zealand | |
100 | Canterbury Health Laboratories | Christchurch | South Island | New Zealand | |
101 | Middlemore Hospital | Auckland | New Zealand | ||
102 | Waikato Hospital | Hamilton | New Zealand | ||
103 | Wellington Hospital | Newtown | New Zealand | 6021 | |
104 | Tauranga Hospital | Tauranga | New Zealand | 3143 | |
105 | Wojewodzki Szpital Specjalistyczny w Legnicy | Legnica | Dolnoslaskie | Poland | |
106 | Szpital Specjalistyczny w Brzozowie | Brzozów | JPodkarpackie | Poland | |
107 | Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi | Łódź | Lódzkie | Poland | |
108 | Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich | Chorzów | Slaskie | Poland | |
109 | Interhem Opieka Szpitalna | Białystok | Poland | ||
110 | Copernicus PL Sp. z o.o. Wojewodzkie Centrum Onkologii | Gdańsk | Poland | ||
111 | Uniwersyteckie Centrum Kliniczne - PPDS | Gdańsk | Poland | ||
112 | Pratia MCM Krakow | Kraków | Poland | ||
113 | Examen sp. z o.o. | Skorzewo | Poland | ||
114 | Hospital Universitario Central de Asturias | Oviedo | Asturias | Spain | |
115 | Hospital Universitario Marques de Valdecilla | Santander | Cantabria | Spain | |
116 | Clinica Universidad Navarra | Pamplona | Navarra | Spain | |
117 | Hospital Clinic de Barcelona | Barcelona | Spain | ||
118 | Hospital de La Santa Creu i Sant Pau | Barcelona | Spain | ||
119 | Hospital del Mar | Barcelona | Spain | ||
120 | Hospital Universitario Germans Trias i Pujol | Barcelona | Spain | ||
121 | Hospital Universitario Vall d'Hebrón - PPDS | Barcelona | Spain | ||
122 | Hospital Universitari de Girona Dr Josep Trueta | Girona | Spain | ||
123 | Hospital Universitario La Paz | Madrid | Spain | ||
124 | Hospital Universitario Ramon y Cajal | Madrid | Spain | ||
125 | Hospital Universitario Puerta de Hierro - Majadahonda | Majadahonda | Spain | ||
126 | Hospital Virgen de La Salud | Toledo | Spain | ||
127 | Skånes Universitetssjukhus i Lund | Lund | Skane | Sweden | |
128 | Södra Älvsborgs Sjukhus Borås | Borås | Sweden | 50182 | |
129 | Sunderby Sjukhus | Lulea | Sweden | ||
130 | Karolinska Universitetssjukhuset Solna | Stockholm | Sweden | 17176 | |
131 | Namik Kemal University | Tekirdağ | Turkey | ||
132 | Aberdeen Royal Infirmary - PPDS | Aberdeen | Aberdeen City | United Kingdom | |
133 | Norfolk and Norwich University Hospital | Norwich | Norfolk | United Kingdom | |
134 | Royal Bournemouth Hospital | Sunderland | Northumberland | United Kingdom | |
135 | Sunderland Royal Hospital | Sunderland | Northumberland | United Kingdom | |
136 | GenesisCare - Oxford | Oxford | Oxfordshire | United Kingdom | |
137 | Birmingham Heartlands Hospital | Birmingham | United Kingdom | ||
138 | Kent and Canterbury Hospital | Canterbury | United Kingdom | CT1 3NG | |
139 | St James University Hospital | Leeds | United Kingdom | ||
140 | Barts Health NHS Trust | London | United Kingdom | ||
141 | Kings College Hospital | London | United Kingdom | ||
142 | The Christie NHS Foundation Trust - PPDS | Manchester | United Kingdom | ||
143 | Nottingham University Hospitals NHS Trust | Nottingham | United Kingdom | ||
144 | Derriford Hospital | Plymouth | United Kingdom | ||
145 | Southampton General Hospital | Southampton | United Kingdom |
Sponsors and Collaborators
- BeiGene
Investigators
- Study Director: Tommi Salmi, MD, BeiGene
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BGB-3111-305
- 2018-001366-42
- CTR20190098