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Trial record 11 of 22 for:    BGB-3111

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

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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

Tracking Information
First Submitted Date  ICMJE February 7, 2017
First Posted Date  ICMJE February 15, 2017
Last Update Posted Date July 19, 2019
Actual Study Start Date  ICMJE January 25, 2017
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 12, 2017)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03053440 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 30, 2018)
  • 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)
  • 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
  • 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
  • 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 ]
  • 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
  • Safety measured by the incidence, timing, and severity of treatment-emergent AEs in Cohort 1 [ Time Frame: Up to 5 years ]
  • The incidence of AEs of Special Interest in Cohort 1 [ Time Frame: Up to 5 years ]
  • New onset of atrial fibrillation and/or ventricular arrhythmia of any NCI-CTCAE v4.03grade [ Time Frame: Up to 5 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 12, 2017)
  • 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)
  • 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
  • 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
  • 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 ]
  • Anti-lymphoma effect in Cohort 1, as measured by any reduction in bone marrow involvement by lymphoplasmacytoid lymphocytes and/or size of lymphadenopathy and/or hepatosplenomegaly [ Time Frame: Up to 5 years ]
  • Safety measured by the incidence, timing, and severity of treatment-emergent AEs in Cohort 1 [ Time Frame: Up to 5 years ]
  • The incidence of AEs of Special Interest in Cohort 1 [ Time Frame: Up to 5 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Comparing BGB-3111 and Ibrutinib in Subjects With Waldenström's Macroglobulinemia (WM)
Official Title  ICMJE 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)
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Waldenström's Macroglobulinemia
Intervention  ICMJE
  • Drug: BGB-3111
    160mg PO BID until progressive disease, unacceptable toxicity, death, withdrawal of consent, or study termination by sponsor
  • Drug: Ibrutinib
    420mg PO QD until progressive disease, unacceptable toxicity, death, withdrawal of consent, or study termination by sponsor
    Other Name: IMBRUVICA
Study Arms  ICMJE
  • 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]
    Intervention: Drug: BGB-3111
  • 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]
    Intervention: Drug: Ibrutinib
  • 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]
    Intervention: Drug: BGB-3111
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: April 30, 2018)
210
Original Estimated Enrollment  ICMJE
 (submitted: February 12, 2017)
167
Estimated Study Completion Date  ICMJE June 2021
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Czechia,   France,   Germany,   Greece,   Italy,   Netherlands,   Poland,   Spain,   Sweden,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03053440
Other Study ID Numbers  ICMJE BGB-3111-302
2016-002980-33 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party BeiGene
Study Sponsor  ICMJE BeiGene
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account BeiGene
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP