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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 181
- 试验地点
- 48
- 主要终点
- Progression Free Survival (PFS) Based on Independent Review Committee (IRC) Assessment - Kaplan Meier Landmark Estimates at Month 54
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Ibrutinib (Drug)
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.
干预措施: Rituximab (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: Rituximab (Drug)
Open-Label Substudy (Ibrutinib)
Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1.
干预措施: Ibrutinib (Drug)
结局指标
主要结局
Progression Free Survival (PFS) Based on Independent Review Committee (IRC) Assessment - Kaplan Meier Landmark Estimates at Month 54
时间窗: Month 54 (median time on study: 49.7 months [Ibr+R and Pbo+R] and 57.9 months [Open-Label Ibr])
PFS was defined as the time from date randomization to date of first IRC-confirmed disease progression (PD) assessed according to the modified VIth International Workshop on Waldenström's Macroglobulinemia (IWWM) criteria (National Comprehensive Cancer Network \[NCCN\] 2014) or death due to any cause, whichever occurs first, regardless of the use of subsequent antineoplastic therapy prior to documented PD or death. As the median PFS was not reached in the Ibrutinib + Rituximab arm at the time of the analysis, Kaplan Meier landmark estimate of the PFS rate at 54 months (that is, the estimated percentage of participants with PFS at Month 54) is presented.
次要结局
- Time to Next Treatment (TnT) Time From the Date of Randomization to the Start Date of Any Subsequent WM Treatment.(Month 54 (median time on study: 49.7 months [Ibr+R and Pbo+R] and 57.9 months [Open-Label Ibr]))
- Percentage of Participants With Sustained Hemoglobin (Hgb) Improvement Up to 3 Years After Last Participant Randomized(Median time on study: 49.7 months (Ibr+R and Pbo+R) and 57.9 months (Open-Label Ibr))
- Overall Response Rate (ORR) Based on IRC Assessment Up to 3 Years After Last Participant Randomized(Median time on study: 49.7 months (Ibr+R and Pbo+R) and 57.9 months (Open-Label Ibr))
- 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(Baseline, 25 weeks)
- Overall Survival (OS) - Kaplan Meier Landmark Estimates at Month 54(Month 54 (median time on study: 49.7 months [Ibr+R and Pbo+R] and 57.9 months [Open-Label Ibr]))