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
Enrollment
145
Locations
2
Arms
57
Anticipated Duration (Months)
4.5
Patients Per Site
0.1
Patients Per Site Per Month

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.

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

ArmIntervention/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

    SiteCityStateCountryPostal Code
    1CARTI Cancer CenterLittle RockArkansasUnited States72205
    2David Geffen School of Medicine at UCLALos AngelesCaliforniaUnited States90095
    3University of California Irvine Medical CenterOrangeCaliforniaUnited States92868
    4Rocky Mountain Cancer Centers (Aurora) - USORAuroraColoradoUnited States80012
    5SCRI Florida Cancer Specialists SouthFort MyersFloridaUnited States33909
    6SCRI Florida Cancer Specialists NorthSaint PetersburgFloridaUnited States33705
    7Augusta UniversityAugustaGeorgiaUnited States30912
    8Illinois Cancer Specialists (Niles) - USORNilesIllinoisUnited States60714
    9Norton Cancer Institute - PavilionLouisvilleKentuckyUnited States40202
    10Dana Farber Cancer InstituteBostonMassachusettsUnited States02215
    11Hattiesburg Hematology and Oncology ClinicHattiesburgMississippiUnited States39401
    12Central Care Cancer CenterBolivarMissouriUnited States65613
    13SCRI HCA Midwest HealthKansas CityMissouriUnited States66211
    14University of Nebraska Medical CenterOmahaNebraskaUnited States68198
    15Comprehensive Cancer Centers of Nevada - USORLas VegasNevadaUnited States89169
    16New Jersey Hematology Oncology Associates LLCBrickNew JerseyUnited States08724
    17Summit Medical GroupFlorham ParkNew JerseyUnited States07932
    18Atlantic Health SystemMorristownNew JerseyUnited States07960
    19Clinical Research Alliance IncLake SuccessNew YorkUnited States11042
    20Columbia University Medical CenterNew YorkNew YorkUnited States10032
    21Duke University Medical CenterDurhamNorth CarolinaUnited States27705
    22Leo W. Jenkins Cancer CenterGreenvilleNorth CarolinaUnited States27834
    23Ohio State University Comprehensive Cancer CenterColumbusOhioUnited States43210
    24Willamette Valley Cancer CenterEugeneOregonUnited States97401
    25Oregon Health and Science UniversityPortlandOregonUnited States97239
    26Greenville Health System Cancer InstituteGreenvilleSouth CarolinaUnited States29601
    27SCRI Tennessee Oncology ChattanoogaChattanoogaTennesseeUnited States37404
    28SCRI Tennessee Oncology NashvilleNashvilleTennesseeUnited States37211
    29Texas Oncology (West 38) - USORAustinTexasUnited States78705
    30Texas Oncology (LOOP) - USORDallasTexasUnited States75230
    31Texas Oncology (Walnut) - USORDallasTexasUnited States75231
    32Texas Oncology-Baylor Charles A. Sammons Cancer CenterDallasTexasUnited States75246
    33Texas Oncology-Fort Worth Cancer CenterFort WorthTexasUnited States76104
    34MD Anderson Cancer CenterHoustonTexasUnited States77030
    35Joe Arrington Cancer Research and Treatment CenterLubbockTexasUnited States79410
    36Texas Oncology - San Antonio Medical Center - USORSan AntonioTexasUnited States78240
    37Texas Oncology (Tyler) - USORTylerTexasUnited States75702
    38Oncology and Hematology Associates of Southwest Virginia, IncRoanokeVirginiaUnited States24014
    39VA Puget Sound Health Care System - NAVREFSeattleWashingtonUnited States98108
    40Fred Hutchinson Cancer Research CenterSeattleWashingtonUnited States98109
    41Medical Oncology AssociatesSpokaneWashingtonUnited States99208
    42Calvary Mater NewcastleNewcastleNew South WalesAustralia
    43Princess Alexandra HospitalWoolloongabbaQueenslandAustralia
    44Box Hill HospitalBox HillVictoraAustralia
    45St Vincents Hospital MelbourneFitzroyVictoriaAustralia
    46Royal Perth HospitalPerthWestern AustraliaAustralia6000
    47Monash Health, Monash Medical CentreClaytonAustralia
    48Peninsula Private HospitalFrankstonAustralia3199
    49Ashford Cancer Centre ResearchKurralta ParkAustralia5037
    50Icon Cancer FoundationMiltonAustralia4066
    51Border Medical OncologyWodongaAustralia
    52UZ BrusselBrusselBrusselsBelgium1090
    53CHU UCL Namur asbl - Site GodinneYvoirNamurBelgium
    54GasthuisZusters AntwerpenWilrijkBelgium
    55Anhui Province HospitalHefeiAnhuiChina230001
    56Peking university Third HospitalBeijingBeijingChina100191
    57Peking Union Medical College HospitalBeijingBeijingChina100730
    58Fujian Medical University Union HospitalFuzhouFujianChina350001
    59Quanzhou First Hospital of Fujian ProvinceQuanzhouFujianChina362002
    60Guangdong General HospitalGuangzhouGuangdongChina
    61Nanfang HospitalGuanzhouGuangdongChina510515
    62Henan Cancer HospitalZhengzhouHenanChina450008
    63Wuhan Union HospitalWuhanHubeiChina430022
    64Jiangsu Province HospitalNanjingJiangsuChina210029
    65The affiliated Hospital of Xuzhou Medical universityXuzhouJiangsuChina221006
    66The First affiliated hospital of Nanchang UniversityNanchangJiangxiChina
    67The First Hospital of Jilin UniversityChangchunJilinChina130021
    68Shengjing Hospital of China Medical UniversityShenyangLiaoningChina110022
    69Tongji Hospital of Tongji UniversityShanghaiShanghaiChina200092
    70West China Hospital ,Sichuan UniversityChengduSichuanChina610041
    71Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical SciencesTianjinTianjinChina300020
    72The First Hospital of Zhejiang ProvinceHangzhouZhejiangChina310003
    73The first affiliated hospital of Wenzhou Medical UniversityWenzhouZhejiangChina325000
    74Beijing Friendship Hospital-Capital Medical UniversityBeijingChina100050
    75Zhongshan hospital of Fudan UniversityShanghaiChina200032
    76Tianjin Medical University Cancer Institute and HospitalTianjinChina300060
    77Fakultni nemocnice BrnoBrnoJihomoravský KrajCzechia
    78Fakultni nemocnice Hradec KraloveHradec KrálovéCzechia
    79Fakultni nemocnice OlomoucOlomoucCzechia
    80Fakultni nemocnice OstravaOstravaCzechia
    81Hopital Prive SevigneCesson-SévignéFrance
    82Centre Hospitalier Departemental de VendeeLa Roche-sur-YonFrance
    83Centre Hospitalier Le MansLe MansFrance
    84Centre Hospitalier Lyon SudPierre BeniteFrance69495
    85CHRU de Poitiers La MiletriePoitiersFrance
    86CHRU BretonneauToursFrance
    87Onkologische Schwerpunktpraxis BielefeldBielefeldNordrhein-WestfalenGermany33604
    88Evangelisches Krankenhaus HammHammNordrhein-WestfalenGermany59063
    89Uniklinik KölnKölnNordrhein-WestfalenGermany50937
    90Gemeinschaftspraxis fur Hamatologie und OnkologieMünsterNordrhein-WestfalenGermany48149
    91Onkoligische Gemeinschaftspraxis Dres. Dörfel/GöhlerDresdenGermany1127
    92Fondazione Policlinico Universitario A GemelliRomaLazioItaly
    93Ospedale San Raffaele S.r.l. - PPDSMilanMilanoItaly
    94ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda Ca' GrandaMilanoItaly
    95Azienda Ospedaliera Città della Salute e della Scienza di TorinoTorinoItaly10126
    96Albert Schweitzer ZiekenhuisDordrechtZuid-HollandNetherlands
    97Gelre ZiekenhuizenApeldoornNetherlands
    98Martini ZiekenhuisGroningenNetherlands
    99North Shore HospitalTakapunaAucklandNew Zealand
    100Canterbury Health LaboratoriesChristchurchSouth IslandNew Zealand
    101Middlemore HospitalAucklandNew Zealand
    102Waikato HospitalHamiltonNew Zealand
    103Wellington HospitalNewtownNew Zealand6021
    104Tauranga HospitalTaurangaNew Zealand3143
    105Wojewodzki Szpital Specjalistyczny w LegnicyLegnicaDolnoslaskiePoland
    106Szpital Specjalistyczny w BrzozowieBrzozówJPodkarpackiePoland
    107Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w LodziŁódźLódzkiePoland
    108Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali MiejskichChorzówSlaskiePoland
    109Interhem Opieka SzpitalnaBiałystokPoland
    110Copernicus PL Sp. z o.o. Wojewodzkie Centrum OnkologiiGdańskPoland
    111Uniwersyteckie Centrum Kliniczne - PPDSGdańskPoland
    112Pratia MCM KrakowKrakówPoland
    113Examen sp. z o.o.SkorzewoPoland
    114Hospital Universitario Central de AsturiasOviedoAsturiasSpain
    115Hospital Universitario Marques de ValdecillaSantanderCantabriaSpain
    116Clinica Universidad NavarraPamplonaNavarraSpain
    117Hospital Clinic de BarcelonaBarcelonaSpain
    118Hospital de La Santa Creu i Sant PauBarcelonaSpain
    119Hospital del MarBarcelonaSpain
    120Hospital Universitario Germans Trias i PujolBarcelonaSpain
    121Hospital Universitario Vall d'Hebrón - PPDSBarcelonaSpain
    122Hospital Universitari de Girona Dr Josep TruetaGironaSpain
    123Hospital Universitario La PazMadridSpain
    124Hospital Universitario Ramon y CajalMadridSpain
    125Hospital Universitario Puerta de Hierro - MajadahondaMajadahondaSpain
    126Hospital Virgen de La SaludToledoSpain
    127Skånes Universitetssjukhus i LundLundSkaneSweden
    128Södra Älvsborgs Sjukhus BoråsBoråsSweden50182
    129Sunderby SjukhusLuleaSweden
    130Karolinska Universitetssjukhuset SolnaStockholmSweden17176
    131Namik Kemal UniversityTekirdağTurkey
    132Aberdeen Royal Infirmary - PPDSAberdeenAberdeen CityUnited Kingdom
    133Norfolk and Norwich University HospitalNorwichNorfolkUnited Kingdom
    134Royal Bournemouth HospitalSunderlandNorthumberlandUnited Kingdom
    135Sunderland Royal HospitalSunderlandNorthumberlandUnited Kingdom
    136GenesisCare - OxfordOxfordOxfordshireUnited Kingdom
    137Birmingham Heartlands HospitalBirminghamUnited Kingdom
    138Kent and Canterbury HospitalCanterburyUnited KingdomCT1 3NG
    139St James University HospitalLeedsUnited Kingdom
    140Barts Health NHS TrustLondonUnited Kingdom
    141Kings College HospitalLondonUnited Kingdom
    142The Christie NHS Foundation Trust - PPDSManchesterUnited Kingdom
    143Nottingham University Hospitals NHS TrustNottinghamUnited Kingdom
    144Derriford HospitalPlymouthUnited Kingdom
    145Southampton General HospitalSouthamptonUnited 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