NCT03474679已完成3 期
A Phase 3 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib in Subjects With Steroid Dependent/Refractory Chronic Graft Versus Host Disease (cGVHD)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 15
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
The purpose of this study is to evaluate efficacy of ibrutinib in Japanese participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) by measuring overall cGVHD response (complete response [CR] and partial response [PR] defined by National Institutes of Health [NIH] consensus development project criteria [2014]).
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Steroid dependent/refractory chronic graft versus host disease (cGVHD) defined as modified National Institutes of Health (NIH) criteria (2014) below at any time post-hematopoietic cell transplant (post-HCT): a) Dependent disease, defined as, when glucocorticoid (prednisolone doses greater than or equal to [>=] 0.25 milligram per kilogram per day (mg/kg/day)or >=0.5 milligram per kilogram (mg/kg) every other day) are needed to prevent recurrence or progression of manifestations as demonstrated by unsuccessful attempts to taper the dose to lower levels on at least 2 occasions, separated by at least 8 weeks. In case of inability to taper the dose to less than or equal to (<=)0.25 mg/kg/day or <=0.5 mg/kg every other day (prednisolone doses) due to recurrence or progression of cGVHD manifestations, it is considered as steroid-dependent disease if the lowest tapering dose of the second occasion is equal or higher than the lowest tapering dose of the first occasion; b) Refractory disease, defined as, when cGVHD manifestations progress despite the use of a regimen containing glucocorticoid (prednisolone at >=1 mg/kg/day for at least 1 week) or persist without improvement despite continued treatment with glucocorticoid (prednisolone at >=0.5 mg/kg/day or 1 mg/kg every other day) for at least 4 weeks
- •Participants must be receiving baseline systemic glucocorticoid therapy for cGVHD at study entry. The dose of steroids must be stable for 14 days prior to starting ibrutinib
- •At the time of trial enrollment, participants may be receiving other immunosuppressive therapies in addition to glucocorticoids. Immunosuppressant doses must be stable for 14 days prior to starting ibrutinib
- •Clinically stable or worsening cGVHD for a minimum of 14 days between screening and Day 1 cGVHD response assessment
- •Karnofsky or Lansky (participants less than [<]16 years) performance status >=60
排除标准
- •Active acute graft versus host disease (GVHD)
- •More than 3 previous systemic treatments for cGVHD. Treatment with glucocorticoids is considered a treatment for cGVHD and should be included in determining the number of previous treatments
- •History of treatment with a tyrosine kinase inhibitor (example [e.g.] imatinib), purine analogs, or other cancer chemotherapy in the 4 weeks prior to starting ibrutinib. Participants may have received ibrutinib pre-transplant for other reasons besides cGVHD such as for the treatment of leukemia or lymphoma
- •History of treatment with monoclonal T and B cell antibodies in the 8 weeks prior to starting ibrutinib
- •Vaccinated with live, attenuated vaccines within 4 weeks of first dose of ibrutinib
研究组 & 干预措施
Ibrutinib
Experimental
Participants will receive 420 milligram (mg) oral ibrutinib once daily starting on Week 1 Day 1, unless they have intervening unacceptable toxicity or meet other criteria for participants discontinuation.
干预措施: Ibrutinib (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: Up to 3 year 6 months
ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR) in the absence of new therapy for chronic graft versus host disease (cGVHD) and absence of progression of underlying disease or death based on the National Institutes of Health (NIH) Consensus Development Project Criteria (2014). CR is defined as resolution of all manifestations in each organ or site; PR is defined as improvement in at least 1 organ or site without progression in any other organ or site; and chronic graft versus host disease (cGVHD) progression is defined as clinically meaningful worsening in 1 or more organs regardless of improvement in other organs.
次要结局
- Apparent Volume of Distribution (Vd/F) of PCI-45227(Day 1 of Weeks 1 and 2)
- Elimination Half-Life (t1/2) of Ibrutinib(Day 1 of Weeks 1 and 2)
- Apparent Clearance (CL/F) of Ibrutinib(Day 1 of Weeks 1 and 2)
- Apparent Volume of Distribution (Vd/F) of Ibrutinib(Day 1 of Weeks 1 and 2)
- Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Ibrutinib(Day 1 of Weeks 1 and 2)
- Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUC [0-last]) of PCI-45227(Day 1 of Weeks 1 and 2)
- Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC [0-24]) of PCI-45227(0 to 24 hours (Day 1 of Weeks 1 and 2))
- Maximum Observed Plasma Concentration (Cmax) of PCI-45227(Day 1 of Weeks 1 and 2)
- Sustained Response Rate(Up to 3 year 6 months)
- Duration of Response (DOR)(Up to 3 year 6 months)
- cGVHD Response Rate at Each Timepoints(Weeks 5, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157)
- Change in the Amount of Corticosteroid Required Over Time(Baseline, Weeks 24, 48, 96, and 144)
- Percentage of Participants With Overall Improvement in Lee cGVHD Symptom Scale Score(Up to 3 year 6 months)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(Up to 3 year 6 months)
- Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUC [0-last]) of Ibrutinib(Day 1 of Weeks 1 and 2)
- Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC [0-24]) of Ibrutinib(0 to 24 hours (Day 1 of Weeks 1 and 2))
- Maximum Observed Plasma Concentration (Cmax) of Ibrutinib(Day 1 of Weeks 1 and 2)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ibrutinib(Day 1 of Weeks 1 and 2)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of PCI-45227(Day 1 of Weeks 1 and 2)
- Elimination Half-Life (t1/2) of PCI-45227(Day 1 of Weeks 1 and 2)
- Apparent Clearance (CL/F) of PCI-45227(Day 1 of Weeks 1 and 2)
- Area Under the Plasma Concentration-time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of PCI-45227(Day 1 of Weeks 1 and 2)
研究者
研究点 (15)
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