Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 11 of 22 for:    BGB-3111

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03053440
Recruitment Status : Active, not recruiting
First Posted : February 15, 2017
Last Update Posted : July 19, 2019
Sponsor:
Information provided by (Responsible Party):
BeiGene

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

Condition or disease Intervention/treatment Phase
Waldenström's Macroglobulinemia Drug: BGB-3111 Drug: Ibrutinib 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 subjects with Waldenström's Macroglobulinemia who require therapy. Subjects will have baseline bone marrow samples assayed for sequencing of the MYD88 gene. Approximately 188 subjects 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. Subjects 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 210 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 : January 25, 2017
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2021


Arm Intervention/treatment
Experimental: Arm A (Experimental Arm-BGB-3111)
Approximately 94 subjects 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 subjects 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 Name: IMBRUVICA

Experimental: Arm C (Experimental Arm-BGB-3111)
Approximately 22 subjects 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




Primary Outcome Measures :
  1. Proportion of subjects 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. [ Time Frame: Up to 3 years ]

Secondary Outcome Measures :
  1. Efficacy measured by major response rate (MRR) in Cohort 1 [ Time Frame: Up to 5 years ]
    MRR defined as the proportion of subjects achieving a best response of response of CR, VGPR, or partial response (PR)

  2. Efficacy measured by duration of response (DOR) in Cohort 1 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to 5 years ]
  5. Anti-lymphoma effect in Cohort 1, measured by any reduction in bone marrow involvement [ Time Frame: 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 [ Time Frame: Up to 5 years ]
  7. The incidence of AEs of Special Interest in Cohort 1 [ Time Frame: Up to 5 years ]
  8. New onset of atrial fibrillation and/or ventricular arrhythmia of any NCI-CTCAE v4.03grade [ Time Frame: Up to 5 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Clinical and definitive histologic diagnosis of WM
  • Measurable disease, requiring treatment
  • Patients 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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03053440


  Hide Study Locations
Locations
Layout table for location information
United States, Arizona
Mayo Clinic
Phoenix, Arizona, United States, 85259
United States, California
City Of Hope National Medical Center
Duarte, California, United States, 91010
University of California San Diego (UCSD) - Moores Cancer Center
La Jolla, California, United States, 92093
Desert Hematology Oncology Medical Group Inc.
Rancho Mirage, California, United States, 92270
United States, Colorado
Colorado Blood Cancer Institute
Denver, Colorado, United States, 80218
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Massachussetts General Hospital
Boston, Massachusetts, United States, 02215
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New York
Weill Cornell Medial College
New York, New York, United States, 10065
United States, Tennessee
The Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Australia, Australian Capital Territory
Canberra Clinical Trials
Garran, Australian Capital Territory, Australia, 2605
Australia, New South Wales
St George Hospital
Kogarah, New South Wales, Australia, 2217
Royal North Shore Hospital
St Leonards, New South Wales, Australia, 2065
Australia, Queensland
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia, 4102
Australia, South Australia
Flinders Medical Centre
Bedford Park, South Australia, Australia
Australia, Victoria
Peninsula Health
Frankston, Victoria, Australia, 3199
Barwon Health, University Hospital Geelong
Geelong, Victoria, Australia, 3220
St. Vincent's Hospital
Melbourne, Victoria, Australia, 3065
Monash Medical Centre
Melbourne, Victoria, Australia
Peter MacCallum Cancer Centre
Melbourne, Victoria, Australia
Australia, Western Australia
Sir Charles Gairdner Hospital
Nedlands, Western Australia, Australia
Belgium
University Hospital Ghent
Gent, Oost-Vlaanderen, Belgium
AZ Sint-Jan Brugge - Oostende - Campus Sint-Jan
Brugge, Belgium, 8000
Czechia
Fakultní nemocnice Hradec Králové
Hradec Králové, Czechia, 50005
Fakultni nemocnice Ostrava
Ostrava, Czechia, 70852
Všeobecná fakultní nemocnice v Praze
Praha, Czechia, 12808
France
CHU Clermont-Ferrand - CHU Estaing
Clermont, France
Institut Paoli Calmettes
Marseille, France
Pitié Salpêtrière Hospital
Paris, France, 75651
Hospital Center Lyon-Sud - Hcl
Pierre-Bénite, France, 69310
Germany
Universitätsklinik Freiburg
Freiburg, Germany, 79106
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Mainz, Germany, 55131
Universitätsklinikum Münster Hämatologie und Onkologie
Munster, Germany, 48149
SRH Kliniken Landkreis Sigmaringen GmbH
Sigmaringen, Germany, 72488
Universitätsklinikum Ulm
Ulm, Germany, 89081
Greece
General Hospital of Athens "Alexandra"
Athens, Attiki, Greece, 11528
Italy
Sant'Orsola-Malpighi Polyclinic
Bologna, Italy, 40138
Azienda Ospedaliera Spedali Civili Di Brescia
Brescia, Italy, 25123
PO A.Ferrarotto, AOU Policlinico-Vittorio Emanuele Catania
Catania, Italy, 95124
Azienda Ospedaliero-Universitaria Careggi
Firenze, Italy, 50134
Irccs Irst
Meldola, Italy
Niguarda Cancer Center Division of Hematology
Milan, Italy, 20133
Azienda Ospedaliera "Maggiore della Carità" di Novara
Novara, Italy, 28100
Università degli studi di Pavia
Pavia, Italy, 27100
Ospedale Civile S.Maria delle
Ravenna, Italy
Università degli Studi di Roma "La Sapienza"
Rome, Italy, 00161
PU A. Gemelli, Universität Cattolica del Sacro Cuore
Rome, Italy, 00168
Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino
Torino, Italy, 10126
Azienda-Ospedaliera Udine
Udine, Italy, 33100
Netherlands
Academisch Medisch Centrum Universiteit van Amsterdam
Amsterdam, Netherlands, 1105 AZ
Universitair Medisch Centrum Utrecht
Utrecht, Netherlands, 3584 CX
Poland
Uniwersytecki Szpital Kliniczny w Białymstoku
Białystok, Poland, 15-276
Szpital Specjalist. w Brzozowie,Podkarpacki Ośrodek Onkologiczny
Brzozów, Poland
Szpital Uniwersytecki nr 2
Bydgoszcz, Poland, 85-168
SPZOZ - Zespół Szpitali Miejskich
Chorzów, Poland, 41-500
Szpitale Pomorskie Sp. z o.o., Szpital Morski im. PCK Gdansk
Gdynia, Poland
Małopolskie Centrum Medyczne
Krakow, Poland, 30-510
Szpital Wojewodzki w Opolu Sp. z o.o.
Opole, Poland
Instytut Hematologii i Transfuzjologii w Warszawie
Warsaw, Poland
Spain
H.U. Vall d´Herbon
Barcelona, Spain, 08035
Hospital Clinic de Barcelona
Barcelona, Spain, 08036
Hospital Duran i Reynals, Instituto Catalán de Oncología
Barcelona, Spain, 08907
Germans Trias i Pujol University Hospital
Barcelona, Spain, 08916
Hospital de Sant Pau
Barcelona, Spain, 8041
ICO-H.U.G. Trias i Pujol
Barcelona, Spain
Hospital Universitario A Coruña
La Coruña, Spain, 15006
Hospital Universitario Fundación Jiménez Díaz
Madrid, Spain, 28040
Clinica Universidad de Navarra
Navarro, Spain
Complejo Asistencial Universitario de Salamanca
Salamanca, Spain, 37007
Hospital Universitari i Politècnic La Fe
Valencia, Spain, 46026
Sweden
Hematology Center Karolinska
Stockholm, Sweden, 14186
United Kingdom
The Royal Bournemouth and Christchurch Hospitals NHS Foundation
Bournemouth, United Kingdom, BH7 7DW
Churchill Hospital
Headington, United Kingdom, OX3 7LE
St James's University Hospital
Leeds, United Kingdom, LS9 7TF
St.Bartholomew's Hospital
London, United Kingdom, EC1A 7BE
University College Hospital
London, United Kingdom, NW1 2PG
Royal Gwent Hospital
Newport, United Kingdom, NP20 2UB
Nottingham University Hospitals NHS Trust
Nottingham, United Kingdom, NG51PB
Derriford Hospital
Plymouth, United Kingdom, PL6 8DH
Sponsors and Collaborators
BeiGene

Layout table for additonal information
Responsible Party: BeiGene
ClinicalTrials.gov Identifier: NCT03053440     History of Changes
Other Study ID Numbers: BGB-3111-302
2016-002980-33 ( EudraCT Number )
First Posted: February 15, 2017    Key Record Dates
Last Update Posted: July 19, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Waldenstrom Macroglobulinemia
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Zanubrutinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action