A Phase II Study of Imatinib Mesylate in Children and Adults With Sclerotic Skin Changes of Chronic Graft-Versus-Host Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Percent Change in Absolute Range of Motion (ROM) From Baseline to 6 Months
研究概览
简要总结
Background:
Chronic graft-versus-host disease (GVHD) is a common complication of stem cell transplant, resulting from the donor's immune cells attacking the cells of the body of the recipient. One effect of GVHD is fibrosis (scarring) of the skin that can lead to impaired function, decreased quality of life and increased risk of death. This is known as sclerotic skin changes of GVHD, or sclerodermatous graft versus host disease (ScGVHD).
Imatinib mesylate (Gleevec) is a drug that has been approved by the Food and Drug Administration to treat cancer in humans and fibrosing conditions in animals.
Objectives:
To see if imatinib mesylate can improve ScGVHD and evaluate its effect on other GVHD symptoms
To assess the side effects of imatinib mesylate in patients with GVHD
To evaluate blood, body fluids and tissue samples in patients to try to better understand the biology of ScGVHD
Eligibility:
Patients 4 years of age and older with ScGVHD
Design:
Initial treatment: Participants take imatinib mesylate tablets once a day for up to 6 months, as long as their GVHD does not get worse and they do not develop unacceptable side effects of the drug.
Evaluations: Participants are evaluated at 1, 3 and 6 months at the National Institutes of Health (NIH) Clinical Center with procedures that may include the following:
Medical history and physical examination
Blood and urine tests
Lung function test
Skin biopsy
Magnetic resonance imaging (MRI) scan
Specialty consultations (e.g., physical or rehabilitative therapy, dentist, eye doctor, dermatologist)
Electrocardiogram (EKG)
Echocardiogram (ultrasound test of the heart)
Muga scan (nuclear medicine test of the heart)
Quality-of-life questionnaires
Apheresis (procedure for collecting quantities of white blood cells)
Office visits with local physician once a week for 1 month, then once every 2 weeks for 5 months
Followup visits at National Institutes of Health (NIH) every 6 months for 1 year
Continuing treatment: Patients who improve continue to receive imatinib mesylate for up to 6 months after their best response and are followed for up to 2 years. Patients who continue to respond or who become worse after stopping treatment may receive additional treatment for up to 2 years.
详细描述
Background:
Chronic graft versus host disease (cGVHD) is a major complication of allogeneic stem cell transplant (alloHSCT). The sclerotic skin manifestations of chronic cutaneous GVHD (ScGVHD) can lead to significant functional impairment and no satisfactory therapy exists to adequately treat this form of cGVHD.
Imatinib mesylate (Gleevec) is a small molecule tyrosine kinase inhibitor with potent activity against platelet derived growth factor receptor (PDGFR) signaling, a key cytokine pathway which has been implicated in fibrotic disease in general, and in extensive cGVHD in particular.
We hypothesize that treatment with imatinib mesylate will reduce the sclerotic manifestations of cGVHD as assessed by quantitative range of motion assessment of an affected joint.
Objectives:
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
- 4 Years 至 —（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
Imatinib mesylate in patients with cGVHD
Cohort 1 - Pts 1-8:Adults: 400mg imatinib mesylate daily; Children: 260mg/m^2 daily (400mg maximum), followed by dose de-escalation for adverse events.
Cohort 2 - Pts 9-20:Adults - 100 mg oral dose daily (increase to 200 mg daily after 28 days if well tolerated). Children - 65 mg/m^2 oral dose daily (increase to 130 mg/m^2 daily after 28 days if well tolerated)
干预措施: Gleevec, STI571(Imatinib Mesylate) (Drug)
结局指标
主要结局
Percent Change in Absolute Range of Motion (ROM) From Baseline to 6 Months
时间窗: 6 months
A change in ROM is 25% or greater from baseline. A partial response required improvement in 25% or more in ROM. Progression required 25% or greater loss of ROM.Patients with negative values in the Table are those who lost ROM. Percent improvement in ROM for 1-3 target joints. For patients with \>1 target joint, the average ROM improvement was calculated. The average percentage change in ROM deficit from baseline to 6 months was obtained based on the number of degrees of ROM change (6 months)/total ROM deficit (baseline) at each joint.
Primary Range of Motion (ROM) Response
时间窗: 6 months
Progressive disease is defined as joint ROM: decrease of \>25% in composite ROM score on 2 consecutive evaluations at least 2 weeks apart, but not greater than 4 weeks apart or steroid pulse: \>1 steroid pulse per 3 month period if administered for sclerotic-type chronic graft versus host disease (ScGVHD). Response is joint ROM: increase of \>25% in composite ROM score. Maximal response is a response with no further improvement over 2 sequential 3-month evaluations. Stable disease does not meet the criteria for progression, response, or maximal response.
次要结局
- Lung Function Score at Baseline and 6 Months(Baseline and 6 Months)
- Number of Participants With Adverse Events(Date treatment consent signed to date off study, approximately, 41 months, 27 days)
- Average Percentage Change in Range of Motion (ROM) Deficit(6 months)
- Total Skin Score at Baseline and 6 Months(Baseline and 6 Months)
- Total Chronic Graft Versus Host Disease (cGVHD) Provider Global Rating Score at Baseline and 6 Months(Baseline and 6 months)
- Change in Immunosuppression(6 months)
研究者
Edward Cowen, M.D.
Principal Investigator
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)