Ibrutinib With Rituximab in Adults With Waldenström's Macroglobulinemia
NCT ID: NCT02165397
Last Updated: 2021-03-03
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE3
181 participants
INTERVENTIONAL
2014-07-07
2019-11-07
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Daratumumab Plus Ibrutinib in Patients With Waldenstrӧm's Macroglobulinemia
NCT03679624
A Study Comparing BGB-3111 and Ibrutinib in Participants With Waldenström's Macroglobulinemia (WM)
NCT03053440
APG-2575 Single Agent or in Combination With Ibrutinib or Rituximab in Patients With Waldenström Macroglobulinemia
NCT04260217
A Study of Ulocuplumab And Ibrutinib in Symptomatic Patients With Mutated CXCR4 Waldenstrom's Macroglobulinemia
NCT03225716
A Study of Pirtobrutinib, Venetoclax, and Rituximab in People With Waldenström's Macroglobulinemia (WM)/Lymphoplasmacytic Lymphoma (LPL)
NCT07231952
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Randomized Study (Ibrutinib + Rituximab)
Ibrutinib: 420 mg (3 capsules x 140 mg) orally administered daily beginning from Day 1. Rituximab: 375 mg/m\^2 intravenous (IV) per package insert weekly for four consecutive weeks, followed by a second four-weekly rituximab course after a three-month interval.
Ibrutinib
Participants will receive 420 mg of Ibrutinib orally.
Rituximab
Participants will receive rituximab 375 mg/m\^2 IV.
Randomized Study (Placebo + Rituximab)
Placebo: 3 capsules of placebo orally administered daily beginning from Day 1. Rituximab: 375 mg/m\^2 IV per package insert weekly for four consecutive weeks, followed by a second four-weekly rituximab course after a three-month interval.
Placebo
Participants will receive placebo capsules orally.
Rituximab
Participants will receive rituximab 375 mg/m\^2 IV.
Open-Label Substudy (Ibrutinib)
Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1.
Ibrutinib
Participants will receive 420 mg of Ibrutinib orally.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Ibrutinib
Participants will receive 420 mg of Ibrutinib orally.
Placebo
Participants will receive placebo capsules orally.
Rituximab
Participants will receive rituximab 375 mg/m\^2 IV.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Centrally confirmed clinicopathological diagnosis of WM
* Measurable disease defined as serum monoclonal immunoglobulin M (IgM) \>0.5 g/dL
* Symptomatic disease meeting at least 1 of the recommendations from the Second International Workshop on Waldenström Macroglobulinemia for requiring treatment
* Hematology and biochemical values within protocol-defined limits
* Men and women ≥ 18 years of age
* Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
Exclusion Criteria
* Disease that is refractory to the last prior rituximab-containing therapy defined as either
* Relapse after the last rituximab-containing therapy \< 12 months since last dose of rituximab, OR
* Failure to achieve at least a minor response (MR) after the last rituximab-containing therapy If the subject meets this exclusion criterion and therefore is excluded from the main randomized study, participation in the non randomized substudy (Arm C) may be considered
* Rituximab treatment within the last 12 months before the first dose of study drug
* Known anaphylaxis or (immunoglobulin E) IgE-mediated hypersensitivity to murine proteins or to any component of rituximab
* Prior exposure to ibrutinib or other Bruton's tyrosine kinase (BTK) inhibitors
* Known bleeding disorders (eg, von Willebrand's disease) or hemophilia
* History of stroke or intracranial hemorrhage within 12 months prior to enrollment.
* Any uncontrolled active systemic infection.
* Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk.
* Currently active, clinically significant cardiovascular disease
* Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor
Eligibility Criteria for Open-label Substudy Treatment Arm C
* Relapse after the last rituximab-containing therapy \<12 months since last dose of rituximab, OR
* Failure to achieve at least a MR after the last rituximab-containing therapy.
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Janssen Research & Development, LLC
INDUSTRY
Pharmacyclics LLC.
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Bernhard Hauns, MD
Role: STUDY_DIRECTOR
Pharmacyclics LLC.
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
University of California Los Angeles
Los Angeles, California, United States
Stanford Cancer Center
Palo Alto, California, United States
Colorado Blood Cancer Institute
Denver, Colorado, United States
Emory University Hospital
Atlanta, Georgia, United States
Northwestern Memorial Hospital
Chicago, Illinois, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Weill Cornell Medical Center
New York, New York, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
The Canberra Hospital
Garran, Australian Capital Territory, Australia
Concord Repartriation General Hospital
Concord, New South Wales, Australia
Flinders Medical Center
Bedford Park, South Australia, Australia
Peter MacCallum Cancer Center
Melbourne, Victoria, Australia
Cross Cancer Institute
Edmonton, Alberta, Canada
Queen Elizabeth II Health Sciences Center
Halifax, Nova Scotia, Canada
Princess Margaret Hospital
Toronto, Ontario, Canada
McGill University Health Center
Montreal, Quebec, Canada
Institut Paoli-Calmettes
Marseille, Bouches-du-Rhône, France
Centre Hospitalier de Saint Brieuc Hopital Yves le Foll
Saint-Brieuc, Finistère, France
Hôtel Dieu
Nantes, Loire-Atlantique, France
CHU de Nancy-Hopital Brabois Adulte
Vandœuvre-lès-Nancy, Meurthe-et-Moselle, France
Hôpital Claude Huriez
Lille, Nord, France
CHU Estaing
Clermont-Ferrand, Puy-de-Dôme, France
Centre Hospitalier Lyon Sud
Pierre-Bénite, Rhône, France
Hopital Henri Mondor
Créteil, , France
Hôpital Saint Louis
Paris, , France
Groupe Hospitalier Pitié Salpétrière
Paris, , France
Stauferklinikum Schwäbisch Gmünd
Mutlangen, Baden-Wurttemberg, Germany
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Mainz, Rhineland-Palatinate, Germany
Universität Des Saarlandes
Homburg, Saarland, Germany
DIAKO Evangelische Diakonie Krankenhaus gGmbH
Bremen, , Germany
LMU Klinikum der Universität München
München, , Germany
University General Hospital of Patras
Pátrai, Achaia, Greece
Alexandra Hospital
Athens, Attica, Greece
University General Hospital of Thessaloniki "AHEPA"
Thessaloniki, Macedonia, Greece
Laiko General Hospital of Athens
Athens, , Greece
Azienda Ospedaliera Città della Salute e della Scienza di Torino
Turin, Piedmont, Italy
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
Milan, , Italy
ASST Grande Ospedale Metropolitano Niguarda
Milan, , Italy
ASST di Pavia - Fondazione IRCCS Policlinico San Matteo di Pavia
Pavia, , Italy
Azienda Ospedaliero Universitaria Santa Maria della Misericordia di Udine
Udine, , Italy
Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, Spain
Hospital Universitario de Salamanca
Salamanca, Castille and León, Spain
Hospital Clinic de Barcelona
Barcelona, , Spain
Hospital de La Santa Creu i Sant Pau
Barcelona, , Spain
Hospital Universitario Infanta Leonor
Madrid, , Spain
Royal Bournemouth Hospital
Bournemouth, Dorset, United Kingdom
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Dimopoulos MA, Tedeschi A, Trotman J, Garcia-Sanz R, Macdonald D, Leblond V, Mahe B, Herbaux C, Tam C, Orsucci L, Palomba ML, Matous JV, Shustik C, Kastritis E, Treon SP, Li J, Salman Z, Graef T, Buske C; iNNOVATE Study Group and the European Consortium for Waldenstrom's Macroglobulinemia. Phase 3 Trial of Ibrutinib plus Rituximab in Waldenstrom's Macroglobulinemia. N Engl J Med. 2018 Jun 21;378(25):2399-2410. doi: 10.1056/NEJMoa1802917. Epub 2018 Jun 1.
Dimopoulos MA, Trotman J, Tedeschi A, Matous JV, Macdonald D, Tam C, Tournilhac O, Ma S, Oriol A, Heffner LT, Shustik C, Garcia-Sanz R, Cornell RF, de Larrea CF, Castillo JJ, Granell M, Kyrtsonis MC, Leblond V, Symeonidis A, Kastritis E, Singh P, Li J, Graef T, Bilotti E, Treon S, Buske C; iNNOVATE Study Group and the European Consortium for Waldenstrom's Macroglobulinemia. Ibrutinib for patients with rituximab-refractory Waldenstrom's macroglobulinaemia (iNNOVATE): an open-label substudy of an international, multicentre, phase 3 trial. Lancet Oncol. 2017 Feb;18(2):241-250. doi: 10.1016/S1470-2045(16)30632-5. Epub 2016 Dec 10.
Guijosa A, Ramirez-Gamero A, Sarosiek S, Branagan AR, von Keudell G, Treon SP, Castillo JJ. Ibrutinib plus rituximab vs ibrutinib monotherapy in patients with Waldenstrom macroglobulinemia: a pooled analysis. Blood Adv. 2025 Sep 23;9(18):4705-4715. doi: 10.1182/bloodadvances.2025016536.
Buske C, Tedeschi A, Trotman J, Garcia-Sanz R, MacDonald D, Leblond V, Mahe B, Herbaux C, Matous JV, Tam CS, Heffner LT, Varettoni M, Palomba ML, Shustik C, Kastritis E, Treon SP, Ping J, Hauns B, Arango-Hisijara I, Dimopoulos MA. Plain Language Summary of the iNNOVATE study: ibrutinib plus rituximab is well-tolerated and effective in people with Waldenstrom's macroglobulinemia. Future Oncol. 2023 Feb;19(5):345-353. doi: 10.2217/fon-2022-1015. Epub 2023 Feb 23.
Buske C, Tedeschi A, Trotman J, Garcia-Sanz R, MacDonald D, Leblond V, Mahe B, Herbaux C, Matous JV, Tam CS, Heffner LT, Varettoni M, Palomba ML, Shustik C, Kastritis E, Treon SP, Ping J, Hauns B, Arango-Hisijara I, Dimopoulos MA. Ibrutinib Plus Rituximab Versus Placebo Plus Rituximab for Waldenstrom's Macroglobulinemia: Final Analysis From the Randomized Phase III iNNOVATE Study. J Clin Oncol. 2022 Jan 1;40(1):52-62. doi: 10.1200/JCO.21.00838. Epub 2021 Oct 4.
Trotman J, Buske C, Tedeschi A, Matous JV, MacDonald D, Tam CS, Tournilhac O, Ma S, Treon SP, Oriol A, Ping J, Briso EM, Arango-Hisijara I, Dimopoulos MA. Single-Agent Ibrutinib for Rituximab-Refractory Waldenstrom Macroglobulinemia: Final Analysis of the Substudy of the Phase III InnovateTM Trial. Clin Cancer Res. 2021 Nov 1;27(21):5793-5800. doi: 10.1158/1078-0432.CCR-21-1497. Epub 2021 Aug 11.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
PCYC-1127-CA
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.