An Open-label Study of Ibrutinib in Combination With Bortezomib and Dexamethasone in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 74
- 试验地点
- 33
- 主要终点
- Median Progression-Free Survival (PFS)
研究概览
简要总结
This is a Phase 2 open-label study to evaluate the efficacy and safety of ibrutinib in combination with bortezomib and dexamethasone for patients with relapsed or relapsed and refractory multiple myeloma.
详细描述
Bruton's tyrosine kinase (Btk) is an enzyme that is present in hematopoeitic cells other than T cells and is necessary for downstream signal transduction from various hematopoietic receptors including the B cell receptor as well as some Fc, chemokine and adhesion receptors, and is crucial for both B cell development and osteoclastogenesis. Although down-regulated in normal plasma cells, Btk is highly expressed in the malignant cells from many myeloma patients and some cell lines. Ibrutinib is a potent and specific inhibitor of Btk currently in Phase 2 and 3 clinical trials. The current study is designed and intended to determine the safety and efficacy of ibrutinib in combination with bortezomib and dexamethasone in subjects with relapsed/relapsed and refractory multiple myeloma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Subjects with multiple myeloma (MM) who have received 1-3 prior lines of therapy and have demonstrated disease progression since the completion of the most recent treatment regimen. (Subjects may have received prior bortezomib exposure if it does not meet the exclusion criteria for prior proteasome inhibitor use)
- •Measurable disease defined by at least one of the following:
- •Serum monoclonal protein (SPEP) ≥1 g/dL (for subjects with immunoglobulin A (IgA), immunoglobulin D (IgD), immunoglobulin E (IgE) or immunoglobulin M (IgM) multiple myeloma SPEP ≥0.5 g/dL)
- •Urine monoclonal protein (UPEP) ≥200 mg by 24 hour urine electrophoresis
- •Adequate hematologic, hepatic and renal function
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
排除标准
- •Subject must not have primary refractory disease
- •Refractory or non-responsive to prior proteasome inhibitor (PI) therapy (bortezomib or carfilzomib)
- •Peripheral neuropathy Grade ≥2 or Grade 1 with pain at Screening
- •Plasma cell leukemia, primary amyloidosis, or POEMS syndrome
- •Unable to swallow capsules or disease significantly affecting gastrointestinal function
- •Requires treatment with strong CYP3A inhibitors
- •Women who are pregnant or breast feeding
研究组 & 干预措施
Ibrutinib+ Bortezomib+ Dexamethasone
干预措施: Ibrutinib (Drug)
Ibrutinib+ Bortezomib+ Dexamethasone
干预措施: Bortezomib (Drug)
Ibrutinib+ Bortezomib+ Dexamethasone
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Median Progression-Free Survival (PFS)
时间窗: The median time on study was 19.6 months (range: 0.16+, 24.64). Participants were evaluated for Progression-Free Survival (PFS) during their entire time on the study.
The primary efficacy endpoint of this study is mPFS. Progression free survival is defined as the time from the date of first dose of study treatment to confirmed disease progression or death from any cause, whichever occurs first.
次要结局
- Progression Free Survival (PFS) at Landmark Points - 20 Months(The median time on study was 19.6 months (range: 0.16+, 24.64), with the 20 month Progression-Free Survival (PFS) rate presented based on Kaplan-Meier estimates.)
- Safety and Tolerability of Ibrutinib in Combination With Bortezomib and Dexamethasone as Measured by the Number of Participants With Adverse Events.(From first dose of Ibrutinib to within 30 days of last dose for each participant or until study closure. This is the median treatment duration for Ibrutinib of 5.7 months (range: 0.1 - 23.7 months) +30 days (Adverse Events collection period).)
- Duration of Response (DOR)(The median time on study was 19.6 months (range: 0.16+, 24.64).)
- Overall Response Rate (ORR)(The median time on study was 19.6 months (range: 0.16+, 24.64). Participants were evaluated for Overall Response (OR) during the entire time on the study.)
- Time to Progression (TTP)(The median time on study was 19.6 months (range: 0.16+, 24.64).)
- Overall Survival (OS) at 24 Months(The median time on study was 19.6 months (0.16+, 24.64), with the 24 month Overall Survival (OS) rate presented based on Kaplan-Meier estimates.)