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

Sponsor
BeiGene (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03734016
Collaborator
(none)
652
145
2
57
4.5
0.1

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
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

Study Type:
Interventional
Actual Enrollment :
652 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Nov 1, 2018
Anticipated Primary Completion Date :
Jan 1, 2023
Anticipated Study Completion Date :
Aug 1, 2023

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:
  • BGB-3111
  • Active Comparator: Ibrutinib

    Ibrutinib will be orally administered until disease progression or unacceptable toxicity.

    Drug: Ibrutinib
    Ibrutinib 420 mg orally once daily
    Other Names:
  • Imbruvica
  • Outcome Measures

    Primary Outcome Measures

    1. Overall response rate determined by investigator assessment [Up to 50 months]

    Secondary Outcome Measures

    1. Progression-free survival determined by independent central review [Up to 50 months]

    2. Progression-free survival determined by investigator assessment [Up to 51 months]

    3. Duration of response determined by investigator assessment [Up to 51 months]

    4. Duration of response determined by independent central review [Up to 51 months]

    5. Time to treatment failure [Up to 51 months]

    6. Overall survival [Up to 51 months]

    7. Patient reported outcomes as assessed by EORTC-QLQ-C30 [Up to 51 months]

    8. Patient reported outcomes as assessed by EQ-5D-5L [Up to 51 months]

    9. Incidence of adverse events as assessed by CTCAE v4.03 [Safety and Tolerability] [51 months]

    10. 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

    11. Overall response rate determined by independent central review [51 months]

    Other Outcome Measures

    1. Correlation between prognostic and predictive biomarkers and clinical outcomes [Up to 51 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Key Inclusion Criteria

    1. Confirmed diagnosis of CLL or SLL that meets the 2008 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 CT/magnetic resonance imaging (MRI)

    5. 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 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.

    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.
    Responsible Party:
    BeiGene
    ClinicalTrials.gov Identifier:
    NCT03734016
    Other Study ID Numbers:
    • BGB-3111-305
    • 2018-001366-42
    • CTR20190098
    First Posted:
    Nov 7, 2018
    Last Update Posted:
    Dec 6, 2021
    Last Verified:
    Dec 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by BeiGene
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Dec 6, 2021