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ASPEN: A Study Comparing BGB-3111 and Ibrutinib in Participants With Waldenström's Macroglobulinemia (WM)

Sponsor
BeiGene (Industry)
Overall Status
Completed
CT.gov ID
NCT03053440
Collaborator
(none)
229
Enrollment
80
Locations
3
Arms
64.8
Actual Duration (Months)
2.9
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is to evaluate the safety, efficacy and clinical benefit of BGB-3111 (Zanubrutinib) vs ibrutinib in participants with MYD88 Mutation Waldenström's Macroglobulinemia.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

This open-label, randomized study will compare the efficacy and safety of the Bruton's Tyrosine Kinase (BTK) inhibitors BGB-3111 and ibrutinib in participants with Waldenström's Macroglobulinemia who require therapy. Participants will have baseline bone marrow samples assayed for sequencing of the MYD88 gene. Approximately 188 participants with the MYD88 mutation will be enrolled onto Cohort 1 and randomized to receive 160 mg BGB-3111 PO BID (treatment Arm A) or to receive 420mg ibrutinib QD (treatment Arm B) until disease progression or unacceptable toxicity. Participants with MYD88 wild type will be enrolled to Cohort 2 and will receive 160 mg BGB-3111 PO BID (treatment Arm C) until disease progressive disease (PD) or unacceptable toxicity, withdrawal of consent, loss to follow-up, or study termination by Sponsor.

Study Design

Study Type:
Interventional
Actual Enrollment :
229 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Randomized, Open-Label, Multicenter Study Comparing the Efficacy and Safety of the Bruton's Tyrosine Kinase (BTK) Inhibitors BGB-3111 and Ibrutinib in Subjects With Waldenström's Macroglobulinemia (WM)
Actual Study Start Date :
Jan 25, 2017
Actual Primary Completion Date :
Jun 21, 2022
Actual Study Completion Date :
Jun 21, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm A (Experimental Arm-BGB-3111)

Approximately 94 participants with the MYD88 mutation will be enrolled in Cohort 1 and receive BGB-3111 in treatment [Arm A]

Drug: BGB-3111
160mg PO BID until progressive disease, unacceptable toxicity, death, withdrawal of consent, or study termination by sponsor
Active Comparator: Arm B (Active Comparator-Ibrutinib)

Approximately 94 participants with the MYD88 mutation will be enrolled in Cohort 1 and receive Ibrutinib in treatment [Arm B]

Drug: Ibrutinib
420mg PO QD until progressive disease, unacceptable toxicity, death, withdrawal of consent, or study termination by sponsor
Other Names:
  • IMBRUVICA

    		•
    Experimental: Arm C (Experimental Arm-BGB-3111)

    Approximately 22 participants found to have MYD88 wild type will be enrolled in Cohort 2 and receive BGB-3111 in treatment [Arm C]

    Drug: BGB-3111
    160mg PO BID until progressive disease, unacceptable toxicity, death, withdrawal of consent, or study termination by sponsor

    Outcome Measures

    Primary Outcome Measures

    1. Proportion of participants achieving either a complete response (CR) or very good partial response (VGPR) in Cohort 1 using an adaptation of the response criteria updated at the Sixth IWWM as assessed by an independent review committee. [Up to 3 years]

    Secondary Outcome Measures

    1. Efficacy measured by major response rate (MRR) in Cohort 1 [Up to 5 years]

      MRR defined as the proportion of participants achieving a best response of response of CR, VGPR, or partial response (PR)

    2. Efficacy measured by duration of response (DOR) in Cohort 1 [Up to 5 years]

      DOR defined as the time from first determination of response (CR, VGPR or PR) until first documentation of progression or death, whichever comes first

    3. Efficacy measured by progression-free survival (PFS) in Cohort 1 [Up to 5 years]

      PFS defined as time from randomization to the first documentation of progression or death, whichever occurs first

    4. Resolution of treatment-precipitating symptoms in Cohort 1, measured by the absence of the symptoms that triggered initiation of study treatment (per the IWWM treatment guidelines) at any point during study treatment [Up to 5 years]

    5. Anti-lymphoma effect in Cohort 1, measured by any reduction in bone marrow involvement [Up to 5 years]

      Anti-lymphoma effect in Cohort 1, measured by any reduction in bone marrow involvement by lymphoplasmacytoid lymphocytes and/or size of lymphadenopathy and/or hepatosplenomegaly and/or splenomegaly by CT scan, at any time during the course of study treatment

    6. Safety measured by the incidence, timing, and severity of treatment-emergent AEs in Cohort 1 [Up to 5 years]

    7. The incidence of AEs of Special Interest in Cohort 1 [Up to 5 years]

    8. New onset of atrial fibrillation and/or ventricular arrhythmia of any NCI-CTCAE v4.03grade [Up to 5 years]

    Eligibility Criteria

    Criteria

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

    • Clinical and definitive histologic diagnosis of WM

    • Measurable disease, requiring treatment

    • Participants with no prior therapy for WM, must be considered inappropriate candidates for treatment with a standard chemoimmunotherapy regimen

    • Age ≥ 18 years old

    • (ECOG) performance status of 0-2

    • Adequate bone marrow function

    • Adequate renal and hepatic function

    • ECHO/MUGA demonstrating left ventricular ejection fraction (LVEF)≥ the lower limit of institutional normal

    • Subjects may be enrolled who relapse after autologous stem cell transplant if they are at least 3 months after transplant, and after allogeneic transplant if they are at least 6 months post transplant.

    • Females of childbearing potential must agree to use highly effective forms of birth control throughout the course of the study and at least up to 90 days after last dose of study drug. Males must have undergone sterilization- vasectomy, or utilize a barrier method

    • Life expectancy of > 4 months

    Key Exclusion Criteria:

    • Prior exposure to a BTK inhibitor

    • Evidence of disease transformation at the time of study entry

    • Corticosteroids given with antineoplastic intent within 7 days, or chemotherapy given with antineoplastic intent, targeted therapy, or radiation therapy within 3 weeks, or antibody-based therapy within 4 weeks of the start of study drug

    • Major surgery within 4 weeks of study treatment

    • Toxicity of ≥ Grade 2 from prior anticancer therapy

    • History of other active malignancies within 2 years of study entry, with exception of (1) adequately treated in-situ carcinoma of cervix; (2) localized basal cell or squamous cell carcinoma of skin; (3) previous malignancy confined and treated locally with curative intent

    • Currently active, clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, any Class 3 or 4 cardiac disease within 6 months of screening

    • QTcF prolongation (defined as a QTcF > 450 msec)

    • Active, clinically significant Electrocardiogram (ECG) abnormalities

    • Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction

    • Uncontrolled active systemic infection or recent infection requiring parenteral anti-microbial therapy

    • Known human immunodeficiency virus (HIV), or active hepatitis B or hepatitis C

    • Pregnant or lactating women

    • Any life-threatening illness, medical condition, organ system dysfunction, need for profound anticoagulation, or bleeding disorder, which, in the investigator's opinion, could compromise the subject's safety

    • Any medications which are strong or moderate cytochrome P450, family 3, subfamily A (CYP3A) inhibitors or strong CYP3A inducers

    NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mayo Clinic Phoenix Arizona United States 85259
    2 City Of Hope National Medical Center Duarte California United States 91010
    3 University of California San Diego (UCSD) - Moores Cancer Center La Jolla California United States 92093
    4 Desert Hematology Oncology Medical Group Inc. Rancho Mirage California United States 92270
    5 Colorado Blood Cancer Institute Denver Colorado United States 80218
    6 Dana-Farber Cancer Institute Boston Massachusetts United States 02215
    7 Massachussetts General Hospital Boston Massachusetts United States 02215
    8 Mayo Clinic Rochester Minnesota United States 55905
    9 Weill Cornell Medial College New York New York United States 10065
    10 The Sarah Cannon Research Institute Nashville Tennessee United States 37203
    11 Seattle Cancer Care Alliance Seattle Washington United States 98109
    12 Woden Dermatology Phillip Australian Capital Territory Australia 2606
    13 St George Hospital Kogarah New South Wales Australia 2217
    14 Royal North Shore Hospital St Leonards New South Wales Australia 2065
    15 Princess Alexandra Hospital Woolloongabba Queensland Australia 4102
    16 Flinders Medical Centre Bedford Park South Australia Australia
    17 Peninsula Health Frankston Victoria Australia 3199
    18 Barwon Health, University Hospital Geelong Geelong Victoria Australia 3220
    19 St. Vincent's Hospital Melbourne Victoria Australia 3065
    20 Monash Medical Centre Melbourne Victoria Australia
    21 Peter MacCallum Cancer Centre Melbourne Victoria Australia
    22 Sir Charles Gairdner Hospital Nedlands Western Australia Australia
    23 University Hospital Ghent Gent Oost-Vlaanderen Belgium
    24 AZ Sint-Jan Brugge - Oostende - Campus Sint-Jan Brugge Belgium 8000
    25 Fakultní nemocnice Hradec Králové Hradec Králové Czechia 50005
    26 Fakultni nemocnice Ostrava Ostrava Czechia 70852
    27 Všeobecná fakultní nemocnice v Praze Praha Czechia 12808
    28 CHU Clermont-Ferrand - CHU Estaing Clermont France
    29 Centre Leon Berard Lyon France 69008
    30 Institut Paoli Calmettes Marseille France
    31 Pitié Salpêtrière Hospital Paris France 75651
    32 Universitätsklinik Freiburg Freiburg Germany 79106
    33 Universitätsmedizin der Johannes Gutenberg-Universität Mainz Mainz Germany 55131
    34 Universitätsklinikum Münster Hämatologie und Onkologie Munster Germany 48149
    35 SRH Kliniken Landkreis Sigmaringen GmbH Sigmaringen Germany 72488
    36 Universitätsklinikum Ulm Ulm Germany 89081
    37 General Hospital of Athens "Alexandra" Athens Attiki Greece 11528
    38 Sant'Orsola-Malpighi Polyclinic Bologna Italy 40138
    39 Azienda Ospedaliera Spedali Civili Di Brescia Brescia Italy 25123
    40 PO A.Ferrarotto, AOU Policlinico-Vittorio Emanuele Catania Catania Italy 95124
    41 Azienda Ospedaliero-Universitaria Careggi Firenze Italy 50134
    42 Irccs Irst Meldola Italy
    43 Niguarda Cancer Center Division of Hematology Milan Italy 20133
    44 Azienda Ospedaliera "Maggiore della Carità" di Novara Novara Italy 28100
    45 Università degli studi di Pavia Pavia Italy 27100
    46 Ospedale Civile S.Maria delle Ravenna Italy
    47 Università degli Studi di Roma "La Sapienza" Rome Italy 00161
    48 PU A. Gemelli, Universität Cattolica del Sacro Cuore Rome Italy 00168
    49 Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino Torino Italy 10126
    50 Azienda-Ospedaliera Udine Udine Italy 33100
    51 Academisch Medisch Centrum Universiteit van Amsterdam Amsterdam Netherlands 1105 AZ
    52 Universitair Medisch Centrum Utrecht Utrecht Netherlands 3584 CX
    53 Uniwersytecki Szpital Kliniczny w Białymstoku Białystok Poland 15-276
    54 Szpital Specjalist. w Brzozowie,Podkarpacki Ośrodek Onkologiczny Brzozów Poland
    55 Szpital Uniwersytecki nr 2 Bydgoszcz Poland 85-168
    56 SPZOZ - Zespół Szpitali Miejskich Chorzów Poland 41-500
    57 Szpitale Pomorskie Sp. z o.o., Szpital Morski im. PCK Gdansk Gdynia Poland
    58 Małopolskie Centrum Medyczne Krakow Poland 30-510
    59 Szpital Wojewodzki w Opolu Sp. z o.o. Opole Poland
    60 Instytut Hematologii i Transfuzjologii w Warszawie Warsaw Poland
    61 H.U. Vall d´Herbon Barcelona Spain 08035
    62 Hospital Clinic de Barcelona Barcelona Spain 08036
    63 Hospital Duran i Reynals, Instituto Catalán de Oncología Barcelona Spain 08907
    64 Germans Trias i Pujol University Hospital Barcelona Spain 08916
    65 Hospital de Sant Pau Barcelona Spain 8041
    66 ICO-H.U.G. Trias i Pujol Barcelona Spain
    67 Hospital Universitario A Coruña La Coruña Spain 15006
    68 Hospital Universitario Fundación Jiménez Díaz Madrid Spain 28040
    69 Clinica Universidad de Navarra Navarro Spain
    70 Complejo Asistencial Universitario de Salamanca Salamanca Spain 37007
    71 Hospital Universitari i Politècnic La Fe Valencia Spain 46026
    72 Hematology Center Karolinska Stockholm Sweden 14186
    73 The Royal Bournemouth and Christchurch Hospitals NHS Foundation Bournemouth United Kingdom BH7 7DW
    74 Churchill Hospital Headington United Kingdom OX3 7LE
    75 St James's University Hospital Leeds United Kingdom LS9 7TF
    76 St.Bartholomew's Hospital London United Kingdom EC1A 7BE
    77 University College Hospital London United Kingdom NW1 2PG
    78 Royal Gwent Hospital Newport United Kingdom NP20 2UB
    79 Nottingham University Hospitals NHS Trust Nottingham United Kingdom NG51PB
    80 Derriford Hospital Plymouth United Kingdom PL6 8DH

    Sponsors and Collaborators

    • BeiGene

    Investigators

    • Study Director: Aileen Cohen, MD, BeiGene

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    BeiGene
    ClinicalTrials.gov Identifier:
    NCT03053440
    Other Study ID Numbers:
    • BGB-3111-302
    • 2016-002980-33
    First Posted:
    Feb 15, 2017
    Last Update Posted:
    Jul 7, 2022
    Last Verified:
    Jul 1, 2022
    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
    Additional relevant MeSH terms:
    Waldenstrom Macroglobulinemia
    Zanubrutinib

    Study Results

    No Results Posted as of Jul 7, 2022