A Multicenter Open-Label Phase 1b/2 Study of Ibrutinib in Steroid Dependent or Refractory Chronic Graft Versus Host Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 10
- 主要终点
- Phase 2: Overall Response Rate as the Percentage of Participants With Response
研究概览
简要总结
The purpose of this study is to assess the safety and clinical efficacy of ibrutinib in subjects with steroid dependent or refractory Chronic Graft Versus Host Disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Steroid dependent or refractory classic chronic GVHD disease.
- •No more than 3 previous treatments for cGVHD.
- •Receiving baseline systemic glucocorticoid therapy (at stable dose) for cGVHD at study entry.
- •Men and women ≥18 years old.
- •Karnofsky performance status ≥60.
排除标准
- •Known or suspected active acute GVHD.
- •Current treatment with sirolimus AND either cyclosporine or tacrolimus.
- •History of treatment with a tyrosine kinase inhibitor (eg, imatinib), purine analogs or other cancer chemotherapy in the 4 weeks prior to starting study drug.
- •Currently active, clinically significant cardiovascular disease.
- •Uncontrolled infections not responsive to antibiotics, antiviral medicines, or antifungal medicines or a recent infection requiring systemic treatment that was completed ≤14 days before the first dose of study drug.
- •Progressive underlying malignant disease including post-transplant lymphoproliferative disease.
- •History of other malignancy (not including the underlying malignancy that was the indication for transplant)
- •Concomitant use of warfarin or other Vitamin K antagonists
- •Known bleeding disorders or hemophilia.
- •History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
- •Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus (HCV) or hepatitis B virus (HBV).
- •Concurrent use of a strong cytochrome P450(CYP) 3A inhibitor.
研究组 & 干预措施
Phase 1b: Dose Level 1
Subjects receive daily dose of 420 mg of Ibrutinib capsules
干预措施: Ibrutinib (Drug)
Phase 1b: Dose Level 2
Subjects receive daily dose of 280 mg of Ibrutinib capsules
干预措施: Ibrutinib (Drug)
Phase 1b: Dose Level 3
Subjects receive daily dose of 140 mg of Ibrutinib capsules
干预措施: Ibrutinib (Drug)
Phase 2
Subjects receive daily dose of recommended phase 2 dose
干预措施: Ibrutinib (Drug)
结局指标
主要结局
Phase 2: Overall Response Rate as the Percentage of Participants With Response
时间窗: Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.
Overall Response Rate is defined as the proportion of subjects who achieved complete response (CR) or partial response (PR). Response criteria are based on NIH cGVHD Response assessment (Pavletic 2006; Measurement of Therapeutic Response, ASBMT Web site).
Phase 1b: To Evaluate the Safety and Tolerability of Ibrutinib in Steroid Dependent/Refractory cGVHD.
时间窗: 28 treatment days after last subject enrolled in Phase 1 dose level(s).
Number of participants with dose-limiting toxicities as a measure of safety profile to determine recommended dose of ibrutinib
次要结局
- To Evaluate the Clinical Efficacy of Ibrutinib in Steroid Dependent/Refractory cGVHD by Measuring: Duration of Response (DOR)(Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.)
- Corticosteroid Requirement Changes Over Time(Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.)
- Phase 2b: To Evaluate the Safety and Tolerability of Ibrutinib in Steroid Dependent/Refractory cGVHD(From first dose with study drug until 30 days after the last dose of study drug, up to 36.7 months)
- Percentage of Participants With Overall Improvement in Lee cGVHD Symptom Summary Score(Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.)
- Sustained Response Rate as the Percentage of Participants With Sustained Response(Analysis was conducted with the data extraction date of 15 Sep 2017, with a median follow-up time of 25.56 months.)