NCT04111497终止1 期
A Single-Arm, Open-Label, Phase I/II Study of Glasdegib for Sclerotic Chronic Graft-Vs-Host Disease
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 15
- 试验地点
- 3
- 主要终点
- Number of Participants Who Experienced an Adverse Event
研究概览
简要总结
This phase I/II trial studies whether glasdegib is helpful in treating sclerosis associated with chronic graft-versus-host disease. It will also investigate the safety of glasdegib in treating patients with chronic graft-versus-host disease.
详细描述
OUTLINE: This is a phase I/II study.
Patients receive glasdegib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
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
- •Diagnosed with moderate or severe cGVHD according to the 2014 National Institute of Health (NIH) Consensus Criteria
- •Diagnosed with cGVHD-related sclerosis or fasciitis
- •Skin feature score of at least 2 OR
- •Joints and fascia score of at least 1
- •New, stable or progressive sclerosis/fasciitis despite treatment with at least one prior line of systemic therapy for cGVHD
- •Female patients who:
- •Are documented to be postmenopausal or are surgically sterile, OR
- •If of childbearing potential, agree to use at least 1 highly effective method of contraception from the time of signing the informed consent form through 30 days after the last dose of study drug, OR agree to practice true abstinence or exclusively non-heterosexual activity when this is in line with the preferred and usual lifestyle of the subject
- •Male patients who:
- •Are surgically sterile (vasectomized) OR
- •Agree to use at least 1 highly effective method of contraception during the entire study treatment period and through 30 days after the last dose of study drug, OR agree to practice true abstinence or exclusively non-heterosexual activity when this is in line with the preferred and usual lifestyle of the subject, AND
- •Agree to use a condom to prevent potential transmission of investigational drug in seminal fluid
- •Absolute neutrophil count (ANC) > 1000/uL
- •Platelet count > 50 x 10^9/mL
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2 x upper limit of normal (ULN) unless attributed to cGVHD
- •Normal total bilirubin unless attributed to cGVHD
- •Creatinine < 2.0 mg/dl
排除标准
- •Hospitalization for evaluation or management of an infection within the last 8 weeks
- •Known organ dysfunction
- •Uncontrolled cardiovascular disease, including arrhythmias, congestive heart failure
- •Oxygen requirement
- •Addition of any new systemic immunosuppressive treatment within the last 2 weeks
- •* Addition of new systemic immunosuppressive treatment along with glasdegib is also prohibited
- •Corrected QT (QTc) interval > 480 ms
- •Female patients who are lactating or have a positive serum pregnancy test
- •Major surgery within 14 days before enrollment
- •* Does not include placement of venous access device, bone marrow biopsy, GVHD diagnostic biopsy, or other routine procedures in chronic GVHD or post-transplantation care
- •Use of any concomitant medications meds that are prohibited within the past 7 days
- •Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
- •Known intolerance to glasdegib, sonidegib, or vismodegib
- •Non-hematologic malignancy within the past 2 years with the exception of:
- •Adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer
- •Carcinoma in situ of the cervix or breast
- •Prostate cancer of Gleason grade 6 or less with stable prostate-specific antigen levels
- •Cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study
- •Treatment with non-Food and Drug Administration (FDA) approved drug within 21 days of start of this trial
- •Evidence of recurrent or progressive underlying malignant disease
- •Karnofsky performance status < 70%
- •History of non-compliance
- •Life expectancy < 6 months
- •Grade 2 or 3 muscle cramping, or grade 1 muscle cramping that occurs at least weekly
研究组 & 干预措施
Treatment (glasdegib)
Experimental
Patients receive glasdegib PO QD on days 1-28. Cycles repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
干预措施: Glasdegib (Drug)
结局指标
主要结局
Number of Participants Who Experienced an Adverse Event
时间窗: From the start of treatment through 28 days after stopping study drug (Up to 25 months total)
Safety assessments will consist of monitoring and recording adverse events.
次要结局
- Overall Response Rate (ORR) in Sclerotic Manifestations(Up to 12 months after starting glasdegib)
- ORR in All Chronic Graft Versus Host Disease (cGVHD) Manifestations(Up to 12 months after the starting glasdegib)
- Failure-free Survival(At 12 months)
- Symptom Burden Assessment - Absolute Change(Cycle 4 (day 85) and End of Treatment (up through 24 months) [Due to lack of adequate data at cycles 7 (day 169) and 10 (day 253), they are not presented.])
- Quality of Life Assessment(Cycle 4 (day 85) and End of Treatment (up through 24 months) [Due to lack of adequate data at cycles 7 (day 169) and 10 (day 253) they are not presented.])
- Biologic Impact of Hedgehog Pathway Inhibition(Up to 12 months)
- Symptom Burden Assessment - Clinically Meaningful Change(Cycle 4 (day 85) and End of Treatment (up through 24 months) [Due to lack of adequate data at cycles 7 (day 169) and 10 (day 253), they are not presented.])
- Quality of Life Assessment - Clinically Meaningful Change(Cycle 4 (Day 85) and End of Treatment (up through 24 months) [Due to lack of adequate data at cycles 7 (day 169) and 10 (day 253) they are not presented.])
研究者
Stephanie Lee
Professor
Fred Hutchinson Cancer Center
研究点 (3)
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