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

NCT03053440 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: BGB-3111-3022016-002980-33
• Study Type: interventional
• Target: 201
• Locations: 12 countries
• Sites: 58

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.

Conditions

Waldenström's Macroglobulinemia

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to approximately 2 years and 7 months

Secondary Outcomes (13)

• Percentage of Participants Achieving Major Response Rate (MRR) as Assessed by IRC

  Up to approximately 2 years and 7 months

• Duration of Response (DOR) as Assessed by IRC

  Up to approximately 2 years and 7 months

• DOR as Assessed by IRC: Event -Free Rate

  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

  Up to approximately 5 years and 5 months

• DOR as Assessed by the Investigator

  Up to approximately 5 years and 5 months

Study Arms (2)

Arm A : Ibrutinib

EXPERIMENTAL

Participants with the MYD88 mutation received Ibrutinib

Drug: Ibrutinib

Arm B: Zanubrutinib

ACTIVE COMPARATOR

Participants with the MYD88 mutation received zanubrutinib

Drug: BGB-3111

Interventions

BGB-3111 DRUG

160 mg PO BID until progressive disease, unacceptable toxicity, death, withdrawal of consent, or study termination by sponsor

Also known as: Zanubrutinib, Brukinsa

Arm B: Zanubrutinib

Ibrutinib DRUG

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

Also known as: IMBRUVICA

Arm A : Ibrutinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• BeiGene: lead

Study Sites (58)

Mayo Clinic Phoenix

Phoenix, Arizona, 85254, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Sarah Cannon Cancer Center

Nashville, Tennessee, 37203, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Paratus Clinical Research Woden

Canberra, Australian Capital Territory, 2606, Australia

Location

St George Hospital

Kogarah, New South Wales, 2217, Australia

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Princess Alexandra Hospital

Brisbane, Queensland, 4102, Australia

Location

Flinders Medical Centre

Bedford PK, South Australia, 5042, Australia

Location

Monash Health

Clayton, Victoria, 3168, Australia

Location

St Vincents Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

Location

Peninsula Health Frankston

Frankston, Victoria, 3199, Australia

Location

Barwon Health the Geelong Hospital

Geelong, Victoria, 3220, Australia

Location

Peter Maccallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Fakultni Nemocnice Hradec Kralove

Hradec Králové, 50005, Czechia

Location

Fakultni Nemocnice Ostrava

Ostrava, 708 00, Czechia

Location

Vseobecna Fakultni Nemocnice V Praze

Prague, 10000, Czechia

Location

Centre Leon Berard

Lyon, 69373, France

Location

Srh Kliniken Landkreis Sigmaringen

Sigmaringen, 72488, Germany

Location

Universitaetsklinikum Ulm, Innere Medizin Iii

Ulm, 89081, Germany

Location

General Hospital of Athens Alexandra

Athens, 11528, Greece

Location

Policlinico Sorsola Malpighi, Aou Di Bologna

Bologna, 40138, Italy

Location

Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia

Brescia, 25123, Italy

Location

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori Irst

Meldola, 47014, Italy

Location

Niguarda Cancer Center Division of Hematology

Milan, 20162, Italy

Location

Aou Maggiore Della Carita

Novara, 28100, Italy

Location

Irccs Policlinico San Matteo, Universita Degli Studi Di Pavi

Pavia, 27100, Italy

Location

Unita Di Ematologia, Dipartimento Di Ematologia Ed Oncologia

Ravenna, 48121, Italy

Location

Fondazione Policlinico A Gemelli

Roma, 168, Italy

Location

Ao Citta Della Salute E Della Scienza Di Torino Presidio O

Torino, 10126, Italy

Location

Aou Santa Maria Della Misericordia Di Udine

Udine, 33100, Italy

Location

Amsterdam Umc Amc

Amsterdam, 1105 AZ, Netherlands

Location

Universitair Medisch Centrum Utrecht

Utrecht, 3584 CX, Netherlands

Location

Uniwersytecki Szpital Kliniczny W Bialymstoku

Bialystok, 15-276, Poland

Location

Szpital Specjalist W Brzozowie,Podkarpacki Osrodek Onkologiczny

Brzozów, 36-200, Poland

Location

Szpital Uniwersytecki Nr Im Dr Jana Biziela

Bydgoszcz, 85-168, Poland

Location

Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich

Chorzów, 41-500, Poland

Location

Malopolskie Centrum Medyczne Sc

Krakow, 30-510, Poland

Location

Hospital Universitari Germans Trias I Pujol

Badalona, 08916, Spain

Location

Hospital de La Santa Creu I Sant Pau

Barcelona, 08025, Spain

Location

Hospital Universitario Vall Dhebron

Barcelona, 08035, Spain

Location

Ico H Duran I Reynals

Barcelona, 08907, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 8036, Spain

Location

Start Madrid Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitari I Politecnic La Fe

Valencia, 46026, Spain

Location

Karolinska Universitetssjukhuset Solna

Stockholm, 171 76, Sweden

Location

The Royal Bournemouth and Christchurch Hospitals Nhs Foundation

Bournemouth, BH7 7DW, United Kingdom

Location

Churchill Hospital Oxford University Hospital Nhs Trust

Headington, OX3 7LE, United Kingdom

Location

St Jamess Institute of Oncology

Leeds, LS9 7LP, United Kingdom

Location

Barts Health Nhs Trust

London, EC1A 7BE, United Kingdom

Location

University College Hospital

London, NW1 2PG, United Kingdom

Location

Nottingham University Hospitals Nhs Trust

Nottingham, NG51PB, United Kingdom

Location

Plymouth Hospitals Nhs Trust

Plymouth, PL6 8DH, United Kingdom

Location

Related Publications (6)

• 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 RESULT

• 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 DERIVED

• 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 DERIVED

• 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 DERIVED

• 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 DERIVED

• 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 DERIVED

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

zanubrutinib; ibrutinib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: BeiGene

clinicaltrials@beigene.com

+1-877-828-5568

Study Officials

• Study Director

  BeiGene

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2017
• First Posted: February 15, 2017
• Study Start: January 25, 2017
• Primary Completion: June 21, 2022
• Study Completion: June 21, 2022
• Last Updated: October 26, 2024
• Results First Posted: June 9, 2023

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

CZ (3); DE (2); SE (1); US (7); GR (1); IT (10); AU (11); NL (2); PL (5); ES (8); FR (1); GB (7)