TriangleNCT03053440 · CITED IN SOURCE DOCUMENTS
A Study Comparing BGB-3111 and Ibrutinib in Participants With Waldenström's Macroglobulinemia (WM)
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2024-10-26
This study evaluated the safety, efficacy and clinical benefit of BGB-3111 (zanubrutinib) vs ibrutinib in participants with MYD88 Mutation Waldenström's Macroglobulinemia.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
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 Achieving Major Response Rate (MRR) as Assessed by IRC
Duration of Response (DOR) as Assessed by IRC
DOR as Assessed by IRC: Event -Free Rate
Percentage of Participants Achieving Either CR or VGPR in as Assessed by the Investigator
DOR as Assessed by the Investigator
DOR as Assessed by the Investigator: Event-Free Rate
Progression Free Survival (PFS) as Assessed by the IRC
PFS as Assessed by IRC: Event-Free Rate
PFS as Assessed by the Investigator
PFS as Assessed by the Investigator: Event-Free Rate
Percentage of Participants With Resolution of All Treatment-precipitating Symptoms
Percentage of Participants With an Anti-Lymphoma Effect
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- 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 * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 * Adequate bone marrow function * 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 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 \> 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.
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Participants with the MYD88 mutation received Ibrutinib
- intervention Names
- Drug: Ibrutinib
- label
- Arm A : Ibrutinib
- type
- EXPERIMENTAL
- description
- Participants with the MYD88 mutation received zanubrutinib
- intervention Names
- Drug: BGB-3111
- label
- Arm B: Zanubrutinib
- type
- ACTIVE_COMPARATOR
- interventions
- arm Group Labels
- Arm B: Zanubrutinib
- description
- 160 mg PO BID until progressive disease, unacceptable toxicity, death, withdrawal of consent, or study termination by sponsor
- name
- BGB-3111
- other Names
- Zanubrutinib
- Brukinsa
- type
- DRUG
- arm Group Labels
- Arm A : Ibrutinib
- description
- 420 mg PO QD until progressive disease, unacceptable toxicity, death, withdrawal of consent, or study termination by sponsor
- name
- Ibrutinib
- other Names
- IMBRUVICA
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 201
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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.
- 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
- secondary Outcomes
- description
- 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.
- measure
- Percentage of Participants Achieving Major Response Rate (MRR) as Assessed by IRC
- time Frame
- Up to approximately 2 years and 7 months
- description
- 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.
- measure
- Duration of Response (DOR) as Assessed by IRC
- time Frame
- Up to approximately 2 years and 7 months
- description
- Estimated percentage of participants who were event-free based on Kaplan-Meier method.
- measure
- 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)
- description
- 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.
- measure
- Percentage of Participants Achieving Either CR or VGPR in as Assessed by the Investigator
- time Frame
- Up to approximately 5 years and 5 months
- description
- 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
- measure
- DOR as Assessed by the Investigator
- time Frame
- Up to approximately 5 years and 5 months
- description
- Estimated percentage of participants who were event-free based on Kaplan-Meier method.
- measure
- 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)
- description
- 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
- measure
- Progression Free Survival (PFS) as Assessed by the IRC
- time Frame
- Up to approximately 2 years and 7 months
- description
- Estimated percentage of participants who were event-free based on Kaplan-Meier method
- measure
- 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)
- description
- 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.
- measure
- PFS as Assessed by the Investigator
- time Frame
- Up to approximately 5 years and 5 months
- description
- Percentage of participants who were event-free based on Kaplan-Meier method.
- measure
- 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)
- measure
- Percentage of Participants With Resolution of All Treatment-precipitating Symptoms
- time Frame
- Up to approximately 5 years and 5 months
- description
- 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.
- measure
- Percentage of Participants With an Anti-Lymphoma Effect
- time Frame
- Up to approximately 5 years and 5 months
Full study description
- brief Summary
- 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.
Source references
- references
- citation
- 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.
- pmid
- 29869556
- type
- RESULT
- citation
- Garcia-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.
- pmid
- 40924923
- type
- DERIVED
- citation
- Heyman 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.
- pmid
- 39626287
- type
- DERIVED
- citation
- Tedeschi 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.
- pmid
- 39072392
- type
- DERIVED
- citation
- Moslehi 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.
- pmid
- 38502198
- type
- DERIVED
- citation
- Dimopoulos 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.
- pmid
- 37478390
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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- PR 24% 62% Median DOR in months (95% CI) 19.5 (16.6, NE) 18.5 (12.6, NE) 14.2 Waldenström's Macroglobulinemia The efficacy of BRUKINSA was evaluated in ASPEN [NCT03053440], a randomized, active control, open-label trial, comparing BRUKINSA and ibrutinib in patients with MYD88 L265P mutation ( MYD88 MUT ) WM. Patients in Cohort 1
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Preserved source evidence · Not medical advice