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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03053440




Registration number
NCT03053440
Ethics application status
Date submitted
7/02/2017
Date registered
15/02/2017
Date last updated
30/04/2021

Titles & IDs
Public title
A Study Comparing BGB-3111 and Ibrutinib in Participants With Waldenström's Macroglobulinemia (WM)
Scientific 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)
Secondary ID [1] 0 0
2016-002980-33
Secondary ID [2] 0 0
BGB-3111-302
Universal Trial Number (UTN)
Trial acronym
ASPEN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Waldenström's Macroglobulinemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BGB-3111
Treatment: Drugs - Ibrutinib

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]

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]

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]


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

Treatment: Drugs: Ibrutinib
420mg PO QD until progressive disease, unacceptable toxicity, death, withdrawal of consent, or study termination by sponsor

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Up to 3 years
Secondary outcome [1] 0 0
Efficacy measured by major response rate (MRR) in Cohort 1 - MRR defined as the proportion of participants achieving a best response of response of CR, VGPR, or partial response (PR)
Timepoint [1] 0 0
Up to 5 years
Secondary outcome [2] 0 0
Efficacy measured by duration of response (DOR) in Cohort 1 - DOR defined as the time from first determination of response (CR, VGPR or PR) until first documentation of progression or death, whichever comes first
Timepoint [2] 0 0
Up to 5 years
Secondary outcome [3] 0 0
Efficacy measured by progression-free survival (PFS) in Cohort 1 - PFS defined as time from randomization to the first documentation of progression or death, whichever occurs first
Timepoint [3] 0 0
Up to 5 years
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
Up to 5 years
Secondary outcome [5] 0 0
Anti-lymphoma effect in Cohort 1, measured by any reduction in bone marrow involvement - 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
Timepoint [5] 0 0
Up to 5 years
Secondary outcome [6] 0 0
Safety measured by the incidence, timing, and severity of treatment-emergent AEs in Cohort 1
Timepoint [6] 0 0
Up to 5 years
Secondary outcome [7] 0 0
The incidence of AEs of Special Interest in Cohort 1
Timepoint [7] 0 0
Up to 5 years
Secondary outcome [8] 0 0
New onset of atrial fibrillation and/or ventricular arrhythmia of any NCI-CTCAE v4.03grade
Timepoint [8] 0 0
Up to 5 years

Eligibility
Key inclusion criteria
Key

- 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Woden Dermatology - Phillip
Recruitment hospital [2] 0 0
St George Hospital - Kogarah
Recruitment hospital [3] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [4] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [5] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [6] 0 0
Peninsula Health - Frankston
Recruitment hospital [7] 0 0
Barwon Health, University Hospital Geelong - Geelong
Recruitment hospital [8] 0 0
St. Vincent's Hospital - Melbourne
Recruitment hospital [9] 0 0
Monash Medical Centre - Melbourne
Recruitment hospital [10] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [11] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2606 - Phillip
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
2065 - St Leonards
Recruitment postcode(s) [4] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [5] 0 0
- Bedford Park
Recruitment postcode(s) [6] 0 0
3199 - Frankston
Recruitment postcode(s) [7] 0 0
3220 - Geelong
Recruitment postcode(s) [8] 0 0
3065 - Melbourne
Recruitment postcode(s) [9] 0 0
- Melbourne
Recruitment postcode(s) [10] 0 0
- Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
United States of America
State/province [8] 0 0
Washington
Country [9] 0 0
Belgium
State/province [9] 0 0
Oost-Vlaanderen
Country [10] 0 0
Belgium
State/province [10] 0 0
Brugge
Country [11] 0 0
Czechia
State/province [11] 0 0
Hradec Králové
Country [12] 0 0
Czechia
State/province [12] 0 0
Ostrava
Country [13] 0 0
Czechia
State/province [13] 0 0
Praha
Country [14] 0 0
France
State/province [14] 0 0
Clermont
Country [15] 0 0
France
State/province [15] 0 0
Lyon
Country [16] 0 0
France
State/province [16] 0 0
Marseille
Country [17] 0 0
France
State/province [17] 0 0
Paris
Country [18] 0 0
Germany
State/province [18] 0 0
Freiburg
Country [19] 0 0
Germany
State/province [19] 0 0
Mainz
Country [20] 0 0
Germany
State/province [20] 0 0
Munster
Country [21] 0 0
Germany
State/province [21] 0 0
Sigmaringen
Country [22] 0 0
Germany
State/province [22] 0 0
Ulm
Country [23] 0 0
Greece
State/province [23] 0 0
Attiki
Country [24] 0 0
Italy
State/province [24] 0 0
Bologna
Country [25] 0 0
Italy
State/province [25] 0 0
Brescia
Country [26] 0 0
Italy
State/province [26] 0 0
Catania
Country [27] 0 0
Italy
State/province [27] 0 0
Firenze
Country [28] 0 0
Italy
State/province [28] 0 0
Meldola
Country [29] 0 0
Italy
State/province [29] 0 0
Milan
Country [30] 0 0
Italy
State/province [30] 0 0
Novara
Country [31] 0 0
Italy
State/province [31] 0 0
Pavia
Country [32] 0 0
Italy
State/province [32] 0 0
Ravenna
Country [33] 0 0
Italy
State/province [33] 0 0
Rome
Country [34] 0 0
Italy
State/province [34] 0 0
Torino
Country [35] 0 0
Italy
State/province [35] 0 0
Udine
Country [36] 0 0
Netherlands
State/province [36] 0 0
Amsterdam
Country [37] 0 0
Netherlands
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Utrecht
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Poland
State/province [38] 0 0
Bialystok
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Poland
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Brzozów
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Poland
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Bydgoszcz
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Poland
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Chorzów
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Poland
State/province [42] 0 0
Gdynia
Country [43] 0 0
Poland
State/province [43] 0 0
Krakow
Country [44] 0 0
Poland
State/province [44] 0 0
Opole
Country [45] 0 0
Poland
State/province [45] 0 0
Warsaw
Country [46] 0 0
Spain
State/province [46] 0 0
Barcelona
Country [47] 0 0
Spain
State/province [47] 0 0
La Coruña
Country [48] 0 0
Spain
State/province [48] 0 0
Madrid
Country [49] 0 0
Spain
State/province [49] 0 0
Navarro
Country [50] 0 0
Spain
State/province [50] 0 0
Salamanca
Country [51] 0 0
Spain
State/province [51] 0 0
Valencia
Country [52] 0 0
Sweden
State/province [52] 0 0
Stockholm
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Bournemouth
Country [54] 0 0
United Kingdom
State/province [54] 0 0
Headington
Country [55] 0 0
United Kingdom
State/province [55] 0 0
Leeds
Country [56] 0 0
United Kingdom
State/province [56] 0 0
London
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Newport
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Nottingham
Country [59] 0 0
United Kingdom
State/province [59] 0 0
Plymouth

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
BeiGene
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03053440
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Aileen Cohen, MD
Address 0 0
BeiGene
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications