Pilot Study of Safety and Feasibility of Electron Beam Radiotherapy to Treat Refractory Sclerodermatous Chronic Graft-versus-Host Disease
试验速览
- 阶段
- 早期 1 期
- 状态
- 撤回
- 发起方
- 主要终点
- Incidence of toxicity
研究概览
简要总结
This clinical trial tests the safety and side effects of a single small dose (fraction) of electron beam radiotherapy (e-BRT) at 10 Gy dose in treating patients with refractory (did not respond to other treatments) sclerodermatous chronic graft versus host disease (GVHD). GVHD is the most common complication after bone marrow transplant from a donor and happens as a result of donor immune cells attacking patients cells. Fibroblasts are skin cells that produce collagen and fibers and are the cells mainly involved in development of skin GVHD. Previous research has shown that fibroblasts can become fibrocytes (inactive fibroblast) at the fastest rate after receiving 8 Gy or more radiation. Moreover, regulatory T cells (Tregs) are cells from the immune system that can control GVHD and previous research has shown that radiation can increase the number of Tregs. Therefore, e-BRT at 10 Gy has the potential to improve GVHD by increasing the fibroblast to fibrocyte speed and the number of Tregs.
详细描述
PRIMARY OBJECTIVE:
I. To establish safety of 10 Gy of 6 MeV electron beam radiotherapy (e-BRT) administration in subjects with refractory sclerodermatous chronic graft-versus-host disease (cGVHD).
SECONDARY OBJECTIVE:
I. To provide preliminary efficacy data on the anti-fibrotic effects of e-BRT treatment at 4 and 24 weeks.
EXPLORATORY 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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented informed consent of the participant and/or legally authorized representative
- •Agreement to allow the use of archival tissue from diagnostic tumor biopsies
- •If unavailable, exceptions may be granted with study principal investigator (PI) approval
- •Permitting to perform clinical photography
- •Age: >= 18 years
- •Histologically confirmed sclerodermatous GHVD
- •Relapsed/refractory sclerodermatous cGVHD
- •Measurable disease of at least 2.0 cm
- •Failed at least >= 2 prior frontline therapies for sclerodermatous chronic GvHD
- •Fully recovered from the acute toxic effects (except alopecia) to =< Grade 1 to prior therapy
- •Women of childbearing potential (WOCBP): negative urine or serum pregnancy test If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- •To be performed within 7 days prior to Day 1 of protocol therapy unless otherwise stated
- •Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 1 month after the last dose of protocol therapy
- •Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
排除标准
- •Chemotherapy, radiation therapy, biological therapy, immunotherapy within 21 days prior to Day 1 of protocol therapy
- •Herbal medications
- •Females only: Pregnant or breastfeeding
- •Inability to comprehend and sign inform consent
- •Individuals known to carry germline gene mutations in TP53, NBS and ATM.
- •Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
- •Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
结局指标
主要结局
Incidence of toxicity
时间窗: From study initiation of study treatment to day 28
Will be evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) version 5. Unacceptable toxicity (UT) is defined as any local toxicity at the level of the treatment portal that is greater or equal to Grade 3 per National Cancer Institute (NCI) CTCAE version 5.0. The observation window of UT is from receiving study treatment until day 28 or observation of UT, whichever comes first. Patients who receive study treatment and complete UT evaluation will be evaluable for UT. Patients who are inevaluable for UT will be replaced. Toxicity information recorded in each patient will include the type, severity, and the probable association with electron beam radiotherapy (eBRT). Tables will be constructed to summarize the observed incidence by severity and type of toxicity, and dose levels. All patients who receive eBRT will be included as part of an 'as treated' analysis, in toxicities/complications.
次要结局
- Incidence of disease specific response(Up to day 168)