Phase 3
Completed N=181
Ibrutinib With Rituximab in Adults With Waldenström's Macroglobulinemia
Source: ClinicalTrials.gov NCT02165397 ↗Enrolled (actual)
181
Serious AEs
44.8%
Results posted
Nov 2020
Primary outcomePrimary: Progression Free Survival (PFS) Based on Independent Review Committee (IRC) Assessment - Kaplan Meier Landmark Estimates at Month 54 — 68.0; 25.3; 39.7 percentage of participants — p=< 0.0001
◆ Published Evidence
Highly cited
351citations · ~44 / year
Phase 3 Trial of Ibrutinib plus Rituximab in Waldenström's Macroglobulinemia.
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).
Linked Publications (5)
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Phase 3 Trial of Ibrutinib plus Rituximab in Waldenström's Macroglobulinemia.
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Ibrutinib Plus Rituximab Versus Placebo Plus Rituximab for Waldenström's Macroglobulinemia: Final Analysis From the Randomized Phase III iNNOVATE Study.
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Single-Agent Ibrutinib for Rituximab-Refractory Waldenström Macroglobulinemia: Final Analysis of the Substudy of the Phase III Innovate<sup>TM</sup> Trial.
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Ibrutinib plus rituximab vs ibrutinib monotherapy in patients with Waldenström macroglobulinemia: a pooled analysis.
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Plain Language Summary of the iNNOVATE study: ibrutinib plus rituximab is well-tolerated and effective in people with Waldenström's macroglobulinemia.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression Free Survival (PFS) Based on Independent Review Committee (IRC) Assessment - Kaplan Meier Landmark Estimates at Month 54 |
68.0; 25.3; 39.7 | < 0.0001 sig |
| SECONDARY Overall Response Rate (ORR) Based on IRC Assessment Up to 3 Years After Last Participant Randomized |
76.0; 30.7; 77.4 | < 0.0001 sig |
| SECONDARY Time to Next Treatment (TnT) Time From the Date of Randomization to the Start Date of Any Subsequent WM Treatment. |
87.4; 29.4; 64.6 | < 0.0001 sig |
| SECONDARY Percentage of Participants With Sustained Hemoglobin (Hgb) Improvement Up to 3 Years After Last Participant Randomized |
77.3; 42.7; 71.0 | < 0.0001 sig |
| SECONDARY Percentage of Participants With ≥ 3 Points Increase From Baseline by Week 25 in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Subscale Score |
68.0; 54.7; 87.1 | 0.1059 |
| SECONDARY Overall Survival (OS) - Kaplan Meier Landmark Estimates at Month 54 |
86.4; 84.2; 73.4 | 0.643 |
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.
Data sourced from ClinicalTrials.gov (NCT02165397) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.