Multicenter Phase 2 Study of Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, in Relapsed or Refractory Mantle Cell Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 115
- 试验地点
- 18
- 主要终点
- Percentage of Participants Achieving Response
研究概览
简要总结
The primary objective of this study was to evaluate the efficacy of ibrutinib in participants with relapsed or refractory MCL.
The secondary objective was to evaluate the safety of a fixed daily dosing regimen (560 mg daily) of PCI-32765 in this population.
详细描述
This is a Phase 2, open-label, nonrandomized, multicenter, monotherapy study in subjects with histologically documented MCL who have relapsed after ≥ 1 (but not > 5) prior treatment regimens. All subjects meeting eligibility criteria will receive PCI-32765 capsules at a dosage of 560 mg/day once daily for a 28-day cycle until disease progression, unacceptable toxicity, or enrollment in a long-term extension study, whichever occurs earlier.
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
- •Men and women ≥ 18 years of age
- •ECOG performance status of ≤ 2
- •Pathologically confirmed MCL, with documentation of either overexpression of cyclin D1 or t(11;14), and measurable disease on cross sectional imaging that is ≥ 2 cm in the longest diameter and measurable in 2 perpendicular dimensions
- •Documented failure to achieve at least partial response (PR) with, or documented disease progression disease after, the most recent treatment regimen
- •At least 1, but no more than 5, prior treatment regimens for MCL (Note: Subjects having received ≥2 cycles of prior treatment with bortezomib, either as a single agent or as part of a combination therapy regimen, will be considered to be bortezomib-exposed.)
- •Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty
- •Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations)
- •Major exclusion criteria:
- •Prior chemotherapy within 3 weeks, nitrosoureas within 6 weeks, therapeutic anticancer antibodies within 4 weeks, radio- or toxin-immunoconjugates within 10 weeks, radiation therapy within 3 weeks, or major surgery within 2 weeks of first dose of study drug
- •Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of PCI-32765 capsules, or put the study outcomes at undue risk
- •Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
- •Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
- •Any of the following laboratory abnormalities:
- •Absolute neutrophil count (ANC) < 750 cells/mm3 (0.75 x 109/L) unless there is documented bone marrow involvement
- •Platelet count < 50,000 cells/mm3 (50 x 109/L) independent of transfusion support unless there is documented bone marrow involvement
- •Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≥ 3.0 x upper limit of normal (ULN)
- •Creatinine > 2.0 x ULN
排除标准
- 未提供
研究组 & 干预措施
Participants received PCI-32765 560 mg daily
Participants were enrolled and received 560 mg/day dose, stratified into 2 groups based on prior bortezomib exposure.
干预措施: PCI-32765 (Drug)
结局指标
主要结局
Percentage of Participants Achieving Response
时间窗: The median follow-up time on study for all treated participants is 15.3 (range 1.9 - 22.3) months
The primary endpoint of the study was overall response rate (ORR), defined as the proportion of participants who achieved a best overall response of complete response (CR) or partial response (PR), according to the revised International Working Group Criteria for non-Hodgkin's lymphoma (Cheson et al, 2007), as assessed by the investigator. CR is a complete disappearance of all disease, no new lesions, lymph nodes must have regressed and be PET negative, spleen and liver should not be palpable and without nodules, and bone marrow must be negative. PR is a \>/= 50% decrease in the sum of the product of diameters of the target lesions, and \>/= 50% decrease of splenic and hepatic nodules from baseline, no new lesions and no increase in the size of liver, spleen or non-target lesions.
次要结局
- Number of Participants With Treatment Emergent Adverse Events (AEs)(From first dose of PCI-32765 to within 30 days of last dose for each participant or until study closure)
- Mean Change From Baseline to Cycle 5 in EORTC QLQ-C30 Global Health Status Score(From Baseline to Cycle 5 (Week 20))
- PCI-32765 and Its Metabolite (PCI-45227) AUC0-24h After Repeat Dosing of PCI-32765(Performed During the First Month of Receiving PCI-32765)