Phase II Study of Topical Ruxolitinib for Cutaneous Chronic Graft Versus Host Disease (cGVHD)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Percent Change in the Surface Area Measurement of the Target Lesions for Ruxolitinib Treated Versus Placebo Treated Lesions
研究概览
简要总结
Background:
About half the people who have a hematopoietic stem cell transplant using donor cells get Chronic Graft Versus Host Disease (cGVHD). This is chronic graft versus host disease. Immune cells from the donor may see the body tissues in the person as foreign and attack, causing damage. The skin is the most commonly affected organ. Most cGVHD therapies have serious side effects. The cream ruxolitinib inhibits proteins that may play a role in cGVHD.
Objective:
To test the safety and effectiveness of topical ruxolitinib 1.5 percent cream in people with cGVHD of the skin.
Eligibility:
People ages 12 and older with epidermal skin cGVHD
Design:
Participants will be screened with:
Medical history
Physical exam
Blood and urine tests
Skin sample taken (biopsy) to confirm the diagnosis.
At the baseline visit, participants will have:
Skin disease measured with rulers, photographs, and tracing the outline of skin lesions
To complete questionnaires about their symptoms
Blood and urine tests
Some participants will also have a skin biopsy, or total body photographs while they wear only underwear.
Participants will get the ruxolitinib cream and a placebo cream to apply to 2 separate areas of disease. They will do this twice a day for 6 weeks, if they do not have serious side effects. Neither the study team nor the participant will know which area will get ruxolitinib cream and the placebo cream.
Participants will write down:
- When they apply the creams
- Any side effects
- Any medications they take
Most participants will have 4 visits during the 6 weeks they use the creams. Some will have 3 visits and a phone call to see how they are doing. All participants will get a call 4-6 weeks after they stop. Visits include physical exams, blood tests, skin disease measurements, questionnaires, and photos.
详细描述
Background:
- Chronic graft-versus-host disease (cGVHD) develops in approximately half of individuals who undergo allogeneic hematopoietic cell transplant (HCT) and is the leading cause of non-relapse mortality.
- There are no skin-targeted therapies for cutaneous cGVHD that are directed to the pathogenesis of cGVHD.
- Many inflammatory cytokines involved in the pathogenesis of cGVHD signal through the Janus kinase (JAK)-Signal Transducer and Activator of Transcription (STAT) pathway.
- Systemic JAK inhibitors have been studied in GVHD murine models and in humans with improvement at the cellular and clinical level.
- Topical JAK inhibitors have not been studied in cutaneous cGVHD but have demonstrated the ability to decrease inflammatory markers as well as improve clinical findings of psoriasis.
Objectives:
- To determine the safety and tolerability of topical ruxolitinib 1.5% cream in patients with cutaneous cGVHD with epidermal involvement (non-sclerotic form)
- To determine the efficacy of topical ruxolitinib 1.5% cream in patients with cutaneous cGVHD with epidermal involvement (non-sclerotic form)
Eligibility:
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 12 Years 至 100 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Ruxolitinib cream
Investigational cream to 1 location; vehicle cream to 2nd location
干预措施: Ruxolitinib 1.5% cream (Drug)
Vehicle cream
Investigational cream to 1 location; vehicle cream to 2nd location
干预措施: vehicle cream (Drug)
结局指标
主要结局
Percent Change in the Surface Area Measurement of the Target Lesions for Ruxolitinib Treated Versus Placebo Treated Lesions
时间窗: Baseline to week 6
The surface area will be measured by tracing the lesion on transparency paper and measuring the area from the transparency. Differences in remaining active surface area at 6 weeks from baseline between the treated and placebo sites were compared to calculate efficacy. A decrease in active surface area would signify improvement in skin disease.
Number of Participants With Grade 3 and Grade 4 Adverse Events
时间窗: date on study, up to approximately 2 months and 12 days.
Adverse events were measured by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 3 is severe. Grade 4 is life-threatening.
次要结局
- Change in Overall Severity Visual Analog Scale (VAS)(Baseline and week 6)
- Change in Pain Visual Analog Scale (VAS)(Baseline and week 6)
- Change in Pruritus Visual Analog Scale (VAS)(Baseline and week 6)
- Area Under the Serum Concentration Versus Time Curve (AUC) of Ruxolitinib(A pre-dose trough sample will be collected prior to application of the treatment on the day of the follow up visit. After application in clinic, blood samples will be collected at 1 hour, 2 hour and 4 hours.)
- Total Clearance (CL) of Ruxolitinib(A pre-dose trough sample will be collected prior to application of the treatment on the day of the follow up visit. After application in clinic, blood samples will be collected at 1 hour, 2 hour and 4 hours.)
- Half-Life of Ruxolitinib(A pre-dose trough sample will be collected prior to application of the treatment on the day of the follow up visit. After application in clinic, blood samples will be collected at 1 hour, 2 hour and 4 hours.)
研究者
Edward Cowen, M.D.
Principal Investigator
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)