Serial Response and Biomarker-Guided Steroid Taper for Children With GVHD
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 50
- 试验地点
- 22
- 主要终点
- Proportion of CR, VGPR, or PR on day 28 with low cumulative steroid exposure
研究概览
简要总结
The standard treatment for acute graft-vs-host disease (GVHD) is to suppress the activity of the donor immune cells using steroid medications such as prednisone. Although most GVHD, especially in children, responds well to treatment, sometimes (around 1/3 of the time) there is either no response to steroids or the response does not last. In those cases, the GVHD can become dangerous and even life-threatening. Unfortunately, doctors cannot predict who will have a good response to treatment based on symptom severity or initial response to steroids. As a result, nearly all children who develop GVHD are treated with long courses of high dose steroids even though that means many patients receive more treatment than they probably need. Steroid treatment can cause short-term complications like infections, high blood sugar, high blood pressure, muscle weakness, depression, anxiety, and problems sleeping and long-term complications like bone damage, cataracts in the eyes, and decreased growth. The risk of these complications increases with higher doses of steroids and longer treatment. It is important to find ways to decrease the steroid treatment in patients who do not need long courses.
The doctors conducting this research have developed a blood test (GVHD biomarkers) that predicts whether a patient will respond well to steroids. The study team found that children who have low GVHD biomarkers at the start of treatment and for the first two weeks of treatment have a very high response rate to steroids. In this study, the study team will monitor GVHD symptoms and biomarkers during treatment and taper steroids quickly in patients who have GVHD that is expected to respond very well to treatment. The study team will assess how many patients respond well to lower steroid dosing and what steroid complications develop. The study team will also use surveys to obtain the patient's own assessment of their quality of life (down to age 5 years).
详细描述
Pediatric patients with Minnesota standard risk GVHD that is also Ann Arbor 1 by biomarkers will begin treatment at 0.5 mg/kg/d prednisone (or other steroid equivalent). Patients with favorable clinical responses and biomarker scores at weeks 1 and 2 will have their steroid doses tapered quickly on a weekly basis for four weeks. Patients whose GVHD does not respond or have unfavorable biomarker scores will have their steroid doses increased and be removed from study treatment. The primary endpoint is the proportion of patients whose cumulative steroid dose for the first four weeks is less than half of standard dosing.
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
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Newly diagnosed GVHD that meets criteria for Minnesota standard risk (see section 9.0) except isolated skin rash <25% body surface area without other manifestations.
- •Ann Arbor 1 GVHD by biomarkers
- •GVHD not previously treated systemically (topical therapies and non-absorbed steroids are allowed)
- •Any donor type, HLA-match, conditioning regimen is acceptable
- •Age 0-21 years at the time of screening
- •Signed and dated written informed consent obtained from patient or legal representative and assent from pediatric patients capable of providing assent
排除标准
- •Patients treated for GVHD with >0.5 mg/kg/day prednisone for any duration or any steroid treatment for GVHD for more than 2 days prior to screening.
- •Patients receiving corticosteroids >0.1 mg/kg prednisone (or other steroid equivalent) for any indication within 7 days before the onset of acute GVHD except for adrenal insufficiency, premedication for transfusions/IV medications, or intermittent use for symptom control such as nausea/vomiting
- •Relapsed, progressing, or persistent malignancy or other condition (e.g., known declining donor chimerism) requiring withdrawal of systemic immune suppression or donor leukocyte infusion (DLI)
- •Patients with uncontrolled infection (i.e., progressive symptoms related to infection despite treatment, persistently positive microbiological cultures despite treatment, viral reactivations unresponsive to treatment, or any other evidence of severe infection)
- •A clinical presentation resembling de novo chronic GVHD or overlap syndrome developing before or present at the time of enrollment
- •Patients who are pregnant
- •Patients requiring mechanical ventilation or cardiac pressor support
研究组 & 干预措施
Steroid Taper
All enrolled patients start on the same dose of steroids for treatment of GVHD, blood samples are taken at week 1 and 2 post study start and biomarkers plus clinical response determines how steroid treatment is continued
干预措施: Prednisone (Drug)
结局指标
主要结局
Proportion of CR, VGPR, or PR on day 28 with low cumulative steroid exposure
时间窗: study day 28
Proportion of patients with low-risk GVHD (Minnesota standard risk/Ann Arbor 1) who are in CR, VGPR or PR on day 28 and whose cumulative prednisone (or other steroid equivalent) exposure during the first four weeks of treatment is ≤13.5 mg/kg and who have had no intervening additional GVHD therapy for those in CR or VGPR. Complete Response (CR): All evaluable organs (skin, liver, GI tract) stage 0. Very Good Partial Response (VGPR): Any response that approximates a CR with the exception of rash \<25% body surface area. Partial Response (PR): An improvement in one or more organ involved with GVHD symptoms without worsening in others.
次要结局
- Treatment response by day 28(study day 28)
- Serious infection rate(study day 90)
- Overall survival at 6 months(6 months)
- Cumulative steroid dose at study day 90(study day 90)
- Overall survival at 12 months(12 months)
- Cumulative incidence of Non-Relapse Mortality (NRM) at 6 months(6 months)
- Cumulative incidence of chronic GVHD(12 months)
- Cumulative incidence of Non-Relapse Mortality (NRM) at 12 months(12 months)
- Relapse rate at 6 months(6 months)
- Relapse rate at 12 months(12 months)
- Cumulative steroid dose at study day 28(study day 28)
研究者
John Levine
Professor of Internal Medicine and Pediatrics, Director of BMT Clinical Research
Icahn School of Medicine at Mount Sinai