Brief Title
Ibrutinib With Rituximab in Adults With Waldenström's Macroglobulinemia
Official Title
iNNOVATE Study: A Randomized, Double-Blind, Placebo- Controlled, Phase 3 Study of Ibrutinib or Placebo in Combination With Rituximab in Subjects With Waldenström's Macroglobulinemia
Brief Summary
The purpose of this study is to evaluate the safety and efficacy of ibrutinib in combination
with rituximab in participants with Waldenström's macroglobulinemia (WM).
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Progression Free Survival (PFS) Based on Independent Review Committee (IRC) Assessment - Kaplan Meier Landmark Estimates at Month 54
Secondary Outcome
Overall Response Rate (ORR) Based on IRC Assessment Up to 3 Years After Last Participant Randomized
Condition
Waldenström's Macroglobulinemia
Intervention
Ibrutinib
Study Arms / Comparison Groups
Randomized Study (Ibrutinib + Rituximab)
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
181
Start Date
July 7, 2014
Completion Date
November 7, 2019
Primary Completion Date
November 7, 2019
Eligibility Criteria
Eligibility Criteria for the Randomized Study
Inclusion Criteria:
- Untreated or previously treated for WM. Previously treated subjects must have either
documented disease progression or had no response (stable disease) to the most recent
treatment regimen
- 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:
- Known involvement of the central nervous system by WM
- 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
The inclusion/exclusion criteria for the substudy (Arm C) are identical to those described
above for the randomized study but, to be eligible, subjects need to be considered
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 MR after the last rituximab-containing therapy.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Bernhard Hauns, MD, ,
Location Countries
Australia
Location Countries
Australia
Administrative Informations
NCT ID
NCT02165397
Organization ID
PCYC-1127-CA
Responsible Party
Sponsor
Study Sponsor
Pharmacyclics LLC.
Collaborators
Janssen Research & Development, LLC
Study Sponsor
Bernhard Hauns, MD, Study Director, Pharmacyclics LLC (An AbbVie Company)
Verification Date
December 2020