Waldenström's MacroglobulinemiaPhase 3ASPENNCT03053440
A Study Comparing BGB-3111 and Ibrutinib in Participants With Waldenström's Macroglobulinemia (WM)
A Phase 3 study testing BGB-3111 and Ibrutinib in people with Waldenström's Macroglobulinemia, run by BeiGene at 58 sites in 12 countries.
Trial summary
This study evaluated the safety, efficacy and clinical benefit of BGB-3111 (zanubrutinib) vs ibrutinib in participants with MYD88 Mutation Waldenström's Macroglobulinemia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Waldenström's Macroglobulinemia
- What is being tested?
- BGB-3111 and Ibrutinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 201 participants
- Where
- 58 sitesin 12 countries
- Study dates
- 25 Jan 2017to 21 Jun 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Adequate bone marrow function
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- Adequate renal and hepatic function
- Electrocardiogram/multigated acquisition scan (ECHO/MUGA) demonstrating left ventricular ejection fraction (LVEF)≥ the lower limit of institutional normal
- Participants 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
Who cannot join
- 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
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- 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 > 480 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.
Trial locations and contacts
58 sites in 12 countries.
58 sites in 12 countries
Australia11 sites
Flinders Medical Centre
Bedford PK, South Australia, 5042
Princess Alexandra Hospital
Brisbane, Queensland, 4102
Paratus Clinical Research Woden
Canberra, Australian Capital Territory, 2606
Monash Health
Clayton, Victoria, 3168
St Vincents Hospital Melbourne
Fitzroy, Victoria, 3065
Peninsula Health Frankston
Frankston, Victoria, 3199
Barwon Health the Geelong Hospital
Geelong, Victoria, 3220
St George Hospital
Kogarah, New South Wales, 2217
Peter Maccallum Cancer Centre
Melbourne, Victoria, 3000
Sir Charles Gairdner Hospital
Nedlands, Western Australia, 6009
Royal North Shore Hospital
St Leonards, New South Wales, 2065
Italy10 sites
Policlinico Sorsola Malpighi, Aou Di Bologna
Bologna, 40138
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Brescia, 25123
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori Irst
Meldola, 47014
Niguarda Cancer Center Division of Hematology
Milan, 20162
Aou Maggiore Della Carita
Novara, 28100
Irccs Policlinico San Matteo, Universita Degli Studi Di Pavi
Pavia, 27100
Unita Di Ematologia, Dipartimento Di Ematologia Ed Oncologia
Ravenna, 48121
Fondazione Policlinico A Gemelli
Roma, 168
Ao Citta Della Salute E Della Scienza Di Torino Presidio O
Torino, 10126
Aou Santa Maria Della Misericordia Di Udine
Udine, 33100
Spain8 sites
Hospital Universitari Germans Trias I Pujol
Badalona, 08916
Hospital de La Santa Creu I Sant Pau
Barcelona, 08025
Hospital Universitario Vall Dhebron
Barcelona, 08035
Ico H Duran I Reynals
Barcelona, 08907
Hospital Clinic de Barcelona
Barcelona, 8036
Start Madrid Fundacion Jimenez Diaz
Madrid, 28040
Hospital Universitario de Salamanca
Salamanca, 37007
Hospital Universitari I Politecnic La Fe
Valencia, 46026
United States7 sites
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Colorado Blood Cancer Institute
Denver, Colorado, 80218
City of Hope National Medical Center
Duarte, California, 91010
Sarah Cannon Cancer Center
Nashville, Tennessee, 37203
Mayo Clinic Phoenix
Phoenix, Arizona, 85254
Mayo Clinic Rochester
Rochester, Minnesota, 55905
Seattle Cancer Care Alliance
Seattle, Washington, 98109
United Kingdom7 sites
The Royal Bournemouth and Christchurch Hospitals Nhs Foundation
Bournemouth, BH7 7DW
Churchill Hospital Oxford University Hospital Nhs Trust
Headington, OX3 7LE
St Jamess Institute of Oncology
Leeds, LS9 7LP
Barts Health Nhs Trust
London, EC1A 7BE
University College Hospital
London, NW1 2PG
Nottingham University Hospitals Nhs Trust
Nottingham, NG51PB
Plymouth Hospitals Nhs Trust
Plymouth, PL6 8DH
Poland5 sites
Uniwersytecki Szpital Kliniczny W Bialymstoku
Bialystok, 15-276
Szpital Specjalist W Brzozowie,Podkarpacki Osrodek Onkologiczny
Brzozów, 36-200
Szpital Uniwersytecki Nr Im Dr Jana Biziela
Bydgoszcz, 85-168
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich
Chorzów, 41-500
Malopolskie Centrum Medyczne Sc
Krakow, 30-510
Czechia3 sites
Fakultni Nemocnice Hradec Kralove
Hradec Králové, 50005
Fakultni Nemocnice Ostrava
Ostrava, 708 00
Vseobecna Fakultni Nemocnice V Praze
Prague, 10000
Germany2 sites
Srh Kliniken Landkreis Sigmaringen
Sigmaringen, 72488
Universitaetsklinikum Ulm, Innere Medizin Iii
Ulm, 89081
Netherlands2 sites
Amsterdam Umc Amc
Amsterdam, 1105 AZ
Universitair Medisch Centrum Utrecht
Utrecht, 3584 CX
About this study
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)
This study evaluated the safety, efficacy and clinical benefit of BGB-3111 (zanubrutinib) vs ibrutinib in participants with MYD88 Mutation Waldenström's Macroglobulinemia.
Read the detailed description
This open-label, randomized study compared 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 had baseline bone marrow samples assayed for sequencing of the MYD88 gene. 201 participants with the MYD88 mutation were enrolled and randomized to receive 160 mg BGB-3111 orally twice per day (PO BID) (treatment Arm A) or to receive 420mg ibrutinib orally once per day (PO QD) (treatment Arm B) until disease progression or unacceptable toxicity.
- Conditions
- Waldenström's Macroglobulinemia
- Being tested
- BGB-3111, Ibrutinib
- Medical subject headings
- Waldenstrom Macroglobulinemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BGB-3111Drug
Also called Zanubrutinib, Brukinsa
160 mg PO BID until progressive disease, unacceptable toxicity, death, withdrawal of consent, or study termination by sponsor
IbrutinibDrug
Also called IMBRUVICA
420 mg PO QD until progressive disease, unacceptable toxicity, death, withdrawal of consent, or study termination by sponsor
| Study group | Role | What they receive |
|---|---|---|
| Arm A : Ibrutinib | Experimental | Participants with the MYD88 mutation received Ibrutinib Receives: Drug: Ibrutinib |
| Arm B: Zanubrutinib | Active comparator | Participants with the MYD88 mutation received zanubrutinib Receives: Drug: BGB-3111 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Achieving Either a Complete Response (CR) or Very Good Partial Response (VGPR) Using an Adaptation of the Response Criteria Updated at the Sixth International Workshop on WM as Assessed by an Independent Review Committee (IRC)
Percentage of participants with CR, defined as normal serum immunoglobulin M (IgM) levels, disappearance of monoclonal protein by immunofixation, and negative cryoglobulinemia if cryoglobulinemia was positive at baseline, or VGPR, defined as ≥90% reduction in serum IgM level from baseline or normal serum IgM values.
Measured: Up to approximately 2 years and 7 months
Secondary outcomes (13)
Percentage of Participants Achieving Major Response Rate (MRR) as Assessed by IRC
MRR defined as the percentage of participants achieving a best response of response of CR, defined as normal serum IgM levels, disappearance of monoclonal protein by immunofixation, and negative cryoglobulinemia if cryoglobulinemia was positive at baseline, VGPR, defined as ≥90% reduction in serum IgM level from baseline or normal serum IgM values or partial response (PR) defined as ≥50% reduction of serum IgM from baseline.
Measured: Up to approximately 2 years and 7 months
Duration of Response (DOR) as Assessed by IRC
DOR defined as the time from first determination of response (CR, VGPR or PR) until first documentation of progression or death, whichever comes first. CR is defined as normal serum IgM levels, disappearance of monoclonal protein by immunofixation, and negative cryoglobulinemia if cryoglobulinemia was positive at baseline, VGPR, is defined as ≥90% reduction in serum IgM level from baseline or normal serum IgM values or partial response (PR) is defined as ≥50% reduction of serum IgM from baseline.
Measured: Up to approximately 2 years and 7 months
DOR as Assessed by IRC: Event -Free Rate
Estimated percentage of participants who were event-free based on Kaplan-Meier method.
Measured: 12 and 18 months from the date of randomization (up to approximately 2 years and 7 months)
Percentage of Participants Achieving Either CR or VGPR in as Assessed by the Investigator
Percentage of participants with CR, defined as normal serum IgM levels, disappearance of monoclonal protein by immunofixation, and negative cryoglobulinemia if cryoglobulinemia was positive at Baseline, or VGPR, defined as ≥90% reduction in serum IgM level from baseline or normal serum IgM values.
Measured: Up to approximately 5 years and 5 months
DOR as Assessed by the Investigator
DOR is defined as the time from first determination of response (CR, VGPR or PR) until first documentation of progression or death, whichever comes first
Measured: Up to approximately 5 years and 5 months
DOR as Assessed by the Investigator: Event-Free Rate
Estimated percentage of participants who were event-free based on Kaplan-Meier method.
Measured: 24,36 and 48 months from the date of randomization (up to approximately 5 years and 5 months)
Progression Free Survival (PFS) as Assessed by the IRC
PFS as assessed by the IRC, defined as time from randomization to the first documentation of progression (per modified International Workshop on Waldenström macroglobulinemia [IWWM criteria]) or death, whichever occurs first
Measured: Up to approximately 2 years and 7 months
PFS as Assessed by IRC: Event-Free Rate
Estimated percentage of participants who were event-free based on Kaplan-Meier method
Measured: 12 and 18 months from the date of randomization (up to approximately 2 years and 7 months)
PFS as Assessed by the Investigator
PFS as assessed by the Investigator, defined as time from randomization to the first documentation of progression (per modified IWWM criteria) or death, whichever occurs first.
Measured: Up to approximately 5 years and 5 months
PFS as Assessed by the Investigator: Event-Free Rate
Percentage of participants who were event-free based on Kaplan-Meier method.
Measured: 24,36 and 48 months from the date of randomization (up to approximately 5 years and 5 months)
Percentage of Participants With Resolution of All Treatment-precipitating Symptoms
Measured: Up to approximately 5 years and 5 months
Percentage of Participants With an Anti-Lymphoma Effect
Anti-Lymphoma Effect is defined as any reduction in bone marrow involvement by lymphoplasmacytoid lymphocytes and/or size of lymphadenopathy and/or splenomegaly by CT scan, at any time during the course of study treatment.
Measured: Up to approximately 5 years and 5 months
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Measured: Up to approximately 5 years and 5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2017
- Study start25 Jan 2017
- Primary completion21 Jun 2022
- Study completion21 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Waldenström's MacroglobulinemiaStudies of the same condition, open and under way.
- More trials run by BeiGeneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 201 participants (actual)
Sponsor and investigators
- Lead sponsor
- BeiGene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, BeiGene
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03053440
- Sponsor's protocol ID
- BGB-3111-302
- Other IDs
- 2016-002980-33, 2016
- Acronym
- ASPEN
- Status last verified
- Oct 2024
- First submitted
- 7 Feb 2017
- Last updated
- 26 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Tam CS, LeBlond V, Novotny W, Owen RG, Tedeschi A, Atwal S, Cohen A, Huang J, Buske C. A head-to-head Phase III study comparing zanubrutinib versus ibrutinib in patients with Waldenstrom macroglobulinemia. Future Oncol. 2018 Sep;14(22):2229-2237. doi: 10.2217/fon-2018-0163. Epub 2018 Jun 5.
PubMed 29869556Garcia-Sanz R, Owen RG, Jurczak W, Dimopoulos MA, McCarthy H, Cull G, Opat SS, Castillo JJ, Kersten MJ, Wahlin BE, Grosicki S, Prathikanti R, Tian T, Allewelt H, Cohen AC, Tam CS. Outcomes after transition from ibrutinib to zanubrutinib in patients with Waldenstrom macroglobulinemia from the ASPEN study. Blood Adv. 2025 Dec 23;9(24):6538-6546. doi: 10.1182/bloodadvances.2024015596.
PubMed 40924923Heyman BM, Opat SS, Wahlin BE, Dimopoulos MC, Castillo JJ, Tedeschi A, Tam CS, Buske C, Owen RG, Leblond V, Trotman J, Barnes G, Chan WY, Schneider J, Allewelt H, Cohen A, Matous JV. Peripheral neuropathy in the phase 3 ASPEN study of Bruton tyrosine kinase inhibitors for Waldenstrom macroglobulinemia. Blood Adv. 2025 Feb 25;9(4):722-728. doi: 10.1182/bloodadvances.2024014115.
PubMed 39626287Tedeschi A, Tam CS, Owen RG, Buske C, Leblond V, Dimopoulos M, Garcia-Sanz R, Castillo JJ, Trotman J, Treon SP, Yang K, Tang B, Allewelt H, Patel S, Chan WY, Cohen A, Chen S, Barnes G. Health-related quality of life in patients with Waldenstrom macroglobulinemia: results from the ASPEN trial. Future Oncol. 2024;20(25):1789-1798. doi: 10.1080/14796694.2024.2355079. Epub 2024 Jul 29.
PubMed 39072392Moslehi JJ, Furman RR, Tam CS, Salem JE, Flowers CR, Cohen A, Zhang M, Zhang J, Chen L, Ma H, Brown JR. Cardiovascular events reported in patients with B-cell malignancies treated with zanubrutinib. Blood Adv. 2024 May 28;8(10):2478-2490. doi: 10.1182/bloodadvances.2023011641.
PubMed 38502198Dimopoulos MA, Opat S, D'Sa S, Jurczak W, Lee HP, Cull G, Owen RG, Marlton P, Wahlin BE, Garcia-Sanz R, McCarthy H, Mulligan S, Tedeschi A, Castillo JJ, Czyz J, Fernandez de Larrea C, Belada D, Libby E, Matous J, Motta M, Siddiqi T, Tani M, Trneny M, Minnema MC, Buske C, Leblond V, Treon SP, Trotman J, Chan WY, Schneider J, Allewelt H, Patel S, Cohen A, Tam CS. Zanubrutinib Versus Ibrutinib in Symptomatic Waldenstrom Macroglobulinemia: Final Analysis From the Randomized Phase III ASPEN Study. J Clin Oncol. 2023 Nov 20;41(33):5099-5106. doi: 10.1200/JCO.22.02830. Epub 2023 Jul 21.
PubMed 37478390
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03053440
- Acronym / sponsor ID
- ASPEN / BGB-3111-302
- Conditions
- Waldenström's Macroglobulinemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 201 participants (actual)
- Lead sponsor
- BeiGeneIndustry (pharma, biotech, devices)
- Study start
- 25 Jan 2017 (actual)
- Primary completion
- 21 Jun 2022 (actual)
- Study completion
- 21 Jun 2022 (actual)
- First posted
- 15 Feb 2017 (actual)
- Results
- Posted 9 Jun 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluated the safety, efficacy and clinical benefit of BGB-3111 (zanubrutinib) vs ibrutinib in participants with MYD88 Mutation Waldenström's Macroglobulinemia.
Detailed description
This open-label, randomized study compared 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 had baseline bone marrow samples assayed for sequencing of the MYD88 gene. 201 participants with the MYD88 mutation were enrolled and randomized to receive 160 mg BGB-3111 orally twice per day (PO BID) (treatment Arm A) or to receive 420mg ibrutinib orally once per day (PO QD) (treatment Arm B) until disease progression or unacceptable toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A : Ibrutinib | Experimental | Drug: IbrutinibParticipants with the MYD88 mutation received Ibrutinib |
| Arm B: Zanubrutinib | Active comparator | Drug: BGB-3111Participants with the MYD88 mutation received zanubrutinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BGB-3111Also: Zanubrutinib, Brukinsa160 mg PO BID until progressive disease, unacceptable toxicity, death, withdrawal of consent, or study termination by sponsor | Drug | Arm B: Zanubrutinib |
| IbrutinibAlso: IMBRUVICA420 mg PO QD until progressive disease, unacceptable toxicity, death, withdrawal of consent, or study termination by sponsor | Drug | Arm A : Ibrutinib |
Primary outcome
Percentage of Participants Achieving Either a Complete Response (CR) or Very Good Partial Response (VGPR) Using an Adaptation of the Response Criteria Updated at the Sixth International Workshop on WM as Assessed by an Independent Review Committee (IRC)
Time frame: Up to approximately 2 years and 7 months
Percentage of participants with CR, defined as normal serum immunoglobulin M (IgM) levels, disappearance of monoclonal protein by immunofixation, and negative cryoglobulinemia if cryoglobulinemia was positive at baseline, or VGPR, defined as ≥90% reduction in serum IgM level from baseline or normal serum IgM values.
13 secondary outcomes
Percentage of Participants Achieving Major Response Rate (MRR) as Assessed by IRC
Time frame: Up to approximately 2 years and 7 months
Duration of Response (DOR) as Assessed by IRC
Time frame: Up to approximately 2 years and 7 months
DOR as Assessed by IRC: Event -Free Rate
Time frame: 12 and 18 months from the date of randomization (up to approximately 2 years and 7 months)
Percentage of Participants Achieving Either CR or VGPR in as Assessed by the Investigator
Time frame: Up to approximately 5 years and 5 months
DOR as Assessed by the Investigator
Time frame: Up to approximately 5 years and 5 months
DOR as Assessed by the Investigator: Event-Free Rate
Time frame: 24,36 and 48 months from the date of randomization (up to approximately 5 years and 5 months)
Progression Free Survival (PFS) as Assessed by the IRC
Time frame: Up to approximately 2 years and 7 months
PFS as Assessed by IRC: Event-Free Rate
Time frame: 12 and 18 months from the date of randomization (up to approximately 2 years and 7 months)
PFS as Assessed by the Investigator
Time frame: Up to approximately 5 years and 5 months
PFS as Assessed by the Investigator: Event-Free Rate
Time frame: 24,36 and 48 months from the date of randomization (up to approximately 5 years and 5 months)
Percentage of Participants With Resolution of All Treatment-precipitating Symptoms
Time frame: Up to approximately 5 years and 5 months
Percentage of Participants With an Anti-Lymphoma Effect
Time frame: Up to approximately 5 years and 5 months
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Up to approximately 5 years and 5 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 29869556Tam CS, LeBlond V, Novotny W, Owen RG, Tedeschi A, Atwal S, Cohen A, Huang J, Buske C. A head-to-head Phase III study comparing zanubrutinib versus ibrutinib in patients with Waldenstrom macroglobulinemia. Future Oncol. 2018 Sep;14(22):2229-2237. doi: 10.2217/fon-2018-0163. Epub 2018 Jun 5.
- Derived from this study: PubMed 40924923Garcia-Sanz R, Owen RG, Jurczak W, Dimopoulos MA, McCarthy H, Cull G, Opat SS, Castillo JJ, Kersten MJ, Wahlin BE, Grosicki S, Prathikanti R, Tian T, Allewelt H, Cohen AC, Tam CS. Outcomes after transition from ibrutinib to zanubrutinib in patients with Waldenstrom macroglobulinemia from the ASPEN study. Blood Adv. 2025 Dec 23;9(24):6538-6546. doi: 10.1182/bloodadvances.2024015596.
- Derived from this study: PubMed 39626287Heyman BM, Opat SS, Wahlin BE, Dimopoulos MC, Castillo JJ, Tedeschi A, Tam CS, Buske C, Owen RG, Leblond V, Trotman J, Barnes G, Chan WY, Schneider J, Allewelt H, Cohen A, Matous JV. Peripheral neuropathy in the phase 3 ASPEN study of Bruton tyrosine kinase inhibitors for Waldenstrom macroglobulinemia. Blood Adv. 2025 Feb 25;9(4):722-728. doi: 10.1182/bloodadvances.2024014115.
- Derived from this study: PubMed 39072392Tedeschi A, Tam CS, Owen RG, Buske C, Leblond V, Dimopoulos M, Garcia-Sanz R, Castillo JJ, Trotman J, Treon SP, Yang K, Tang B, Allewelt H, Patel S, Chan WY, Cohen A, Chen S, Barnes G. Health-related quality of life in patients with Waldenstrom macroglobulinemia: results from the ASPEN trial. Future Oncol. 2024;20(25):1789-1798. doi: 10.1080/14796694.2024.2355079. Epub 2024 Jul 29.
- Derived from this study: PubMed 38502198Moslehi JJ, Furman RR, Tam CS, Salem JE, Flowers CR, Cohen A, Zhang M, Zhang J, Chen L, Ma H, Brown JR. Cardiovascular events reported in patients with B-cell malignancies treated with zanubrutinib. Blood Adv. 2024 May 28;8(10):2478-2490. doi: 10.1182/bloodadvances.2023011641.
- Derived from this study: PubMed 37478390Dimopoulos MA, Opat S, D'Sa S, Jurczak W, Lee HP, Cull G, Owen RG, Marlton P, Wahlin BE, Garcia-Sanz R, McCarthy H, Mulligan S, Tedeschi A, Castillo JJ, Czyz J, Fernandez de Larrea C, Belada D, Libby E, Matous J, Motta M, Siddiqi T, Tani M, Trneny M, Minnema MC, Buske C, Leblond V, Treon SP, Trotman J, Chan WY, Schneider J, Allewelt H, Patel S, Cohen A, Tam CS. Zanubrutinib Versus Ibrutinib in Symptomatic Waldenstrom Macroglobulinemia: Final Analysis From the Randomized Phase III ASPEN Study. J Clin Oncol. 2023 Nov 20;41(33):5099-5106. doi: 10.1200/JCO.22.02830. Epub 2023 Jul 21.
- Individual participant dataSharing planned: Yes
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Waldenström's Macroglobulinemia, Chronic Lymphocytic Leukemia
Active, not recruitingObservational study
Retrospective-prospective Study to Evaluate Treatment Management and Outcomes of Patients With Waldenström's Macroglobulinemia (WM) Treated in Italy According to the Zanubrutinib (Brukinsa®) Compassionate Use Program (CUP) and in Common Practice Following Commercial Approval.
Waldenström's Macroglobulinemia (WM)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
BeiGene
58 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing BGB-3111 and Ibrutinib in people with Waldenström's Macroglobulinemia, run by BeiGene at 58 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 58 sites in Australia, Italy, Spain, United States, United Kingdom and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Achieving Either a Complete Response (CR) or Very Good Partial Response (VGPR) Using an Adaptation of the Response Criteria Updated at the Sixth International Workshop on WM as Assessed by an Independent Review Committee (IRC) (time frame: Up to approximately 2 years and 7 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03053440, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2024.