A Multicenter, Open-label, Phase 2, Safety and Efficacy Study of the Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, in Subjects With Relapsed or Refractory or de Novo Diffuse Large B-cell Lymphoma (DLBCL)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 78
- 试验地点
- 15
- 主要终点
- Percentage of Patients With an Overall Response to Study Drug
研究概览
简要总结
The purpose of this study is to evaluate the efficacy of ibrutinib (PCI-32765) in relapsed/refractory de novo activated B-cell (ABC) and germinal-cell B-Cell (GCB) Diffuse Large B-cell Lymphoma (DLBCL).
详细描述
The primary objectives of this study were to evaluate the efficacy of ibrutinib administered at 560 mg once per day in relapsed or refractory de novo ABC and GCB DLBCL, and to evaluate the efficacy of ibrutinib administered at 840 mg once per day in relapsed or refractory de novo ABC DLBCL.
The secondary objective was to evaluate the safety and tolerability of a fixed daily oral dosing regimen of ibrutinib in relapsed/refractory de novo DLBCL.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 ≤
- •Pathologically confirmed de novo DLBCL
- •Subjects must have available tissue for central pathology review to be eligible. Treatment Group 2: Subjects will be eligible if they have the non-GCB phenotype, as confirmed by Central IHC testing by the Hans method.
- •Relapsed or refractory disease, defined as either: 1) recurrence of disease after a CR, or 2) PR, SD, or progressive disease (PD) at completion of the treatment regimen preceding entry to the study (residual disease): Subjects must have previously received an appropriate first-line treatment regimen. Subjects who have not received HDT/ASCT must be ineligible for HDT/ASCT
- •Treatment Group 1: Subjects must have ≥ 1 measurable (> 2 cm in longest dimension) disease sites on CT scan. Treatment Group 2: Subjects must have ≥ 1 measurable (> 1.5 cm in longest dimension) disease sites on CT scan.
排除标准
- •Transformed DLBCL or DLBCL with coexistent histologies (eg, FL or MALT).
- •Primary mediastinal (thymic) large B-cell lymphoma.
- •Known central nervous system lymphoma. In addition, for subjects in Treatment Group 2, known leptomeningeal involvement is exclusionary.
- •Certain exclusions on prior therapy
- •Major surgery within 2 weeks of first dose of study drug.
- •Any of the following laboratory abnormalities:
- •ANC < 0.75 x 10^9/L. Treatment Group 2: Eligible subjects must be independent of growth factor support for 7 days prior to the screening lab tests.
- •Platelet count < 50 x 10^9/L independent of transfusion support. Treatment Group 2 only: Eligible subjects must be independent of transfusion support for 7 days prior to the screening lab tests.
- •AST or ALT ≥ 3.0 x upper limit of normal (ULN)
- •Creatinine > 2.0 x ULN
- •Treatment Group 2 only: Hemoglobin < 8.0 g/dL
- •Treatment Group 2 only: Total Bilirubin > 1.5 x ULN
- •Requires or has received anticoagulation treatment with warfarin or equivalent Vitamin K antagonists (eg, phenprocoumon)
- •Treatment Group 2: Requires treatment with a strong cytochrome P450 (CYP) 3A4/5 inhibitor
- •Treatment Group 2: Known bleeding diathesis, eg, von Willebrand's disease, hemophilia.
研究组 & 干预措施
PCI-32765: 560 mg
Treatment Group 1: Subjects received 560 mg of ibrutinib once daily, on a continuous basis.
干预措施: ibrutinib (Drug)
PCI-32765: 840 mg
Treatment Group 2: Subjects received 840 mg of ibrutinib once daily, on a continuous basis.
干预措施: ibrutinib (Drug)
结局指标
主要结局
Percentage of Patients With an Overall Response to Study Drug
时间窗: The median follow up time on the study for all treated participants is 1.7 months (range 0.1- 32.3 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.
次要结局
- Number of Patients With Adverse Events as a Measure of Safety and Tolerability(Adverse events determined to be related to study drug are collected from first dose until study exit (approximately 3 years).)
- Ibrutinib and Its Metabolite (PCI-45227) AUC0-24h After Repeat Dosing of PCI-32765(Performed during the first month of receiving study drug.)