A Randomized, Placebo-Controlled, Multi-Center Study of Oral Beclomethasone Dipropionate With Ten Days of Prednisone for Treatment of Gastrointestinal Graft Vs. Host Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 130
- 试验地点
- 2
- 主要终点
- Treatment failure (that is, flares of GVHD requiring immunosuppressive drug therapy) at study day 50.
研究概览
简要总结
Patients with gastrointestinal graft-vs.-host disease are randomized to oral beclomethasone dipropionate (BDP) 8 mg/day or identical placebo tablets for 50 days, along with a 10-day induction course of prednisone. At study day 10, patients whose symptoms of GVHD are under control undergo a rapid prednisone taper over 7 days, while study drug is continued to study day 50. After discontinuation of study drug at study day 50, patients are followed for 30 additional days, to study day 80. The primary endpoint is treatment failure by day 50, that is, a flare of the symptoms of GVHD that requires immunosuppressive therapy. Secondary endpoints are treatment failure by day 80, treatment-emergent adverse events, and survival at transplant day 200. The hypothesis to be tested is that a topically-active corticosteroid (beclomethasone dipropionate, BDP), taken orally, would allow rapid tapering of prednisone while maintaining control of intestinal GVHD.
详细描述
Patient selection. Patients who develop symptoms of GVHD are evaluated with endoscopy and mucosal biopsy. If biopsy specimens demonstrate histologic findings of GVHD and stool and mucosal biopsy cultures are negative for pathogens, patients are invited to participate. Patients are excluded if diarrhea exceeds one liter per day, or if skin or liver GVHD are present. All patients receive medications for GVHD prophylaxis; patients receiving corticosteroids within 30 days of study entry are excluded. Patients signed informed consent documents approved by Institutional Review Boards.
Formulation of BDP. Immediate release tablets and enteric-coated tablets, each contained 1 mg of BDP (orBec, DOR BioPharma, Miami FL). The dosing regimen was one immediate release and one enteric-coated tablet, taken orally four times daily (total daily dose, 8 mg BDP).
Stratification and randomization. A stratified allocation scheme is used to balance the treatment groups within study centers. Stratifying variables are HLA-matched sibling and use of cutaneous corticosteroids at baseline. Patients receive either BDP or identical placebo tablets.
Treatment plan. Therapy consists of study drugs plus 10 days of prednisone at an initial prednisone dose of 1 mg/kg/day. In patients with control of GVHD symptoms at Study Day 10, prednisone is tapered over 7 days, after which patients were maintained on physiologic replacement doses of prednisone. Patients who do not demonstrate adequate control of GVHD by Study Day 10 are considered treatment failures. Patients receive study drug for 50 days, or until they meet the treatment failure endpoint, or are withdrawn from the study. Patients who are declared treatment failures have study drug discontinued; subsequent treatment for GVHD is dictated by their physicians.
Definitions of treatment failure and efficacy end-points. Treatment failure is a worsening or recurrence of GVHD that requires additional immunosuppressive therapy. The primary efficacy endpoint is the time to treatment failure through Study Day 50. Secondary efficacy endpoints included time to treatment failure through Study Day 80 (30 days after discontinuation of study drug); the proportion who experience treatment failure by Study Days 10, 30, 50, and 80; and the overall survival rate at day-200 days post-transplant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double
入排标准
- 年龄范围
- 0 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Allogeneic hematopoietic cell transplant ≥10 days prior to screening
- •Symptoms consistent with Grade II intestinal GVHD
- •Diagnosis of GVHD confirmed by biopsy
- •Confirmed absence of intestinal infection
- •Demonstrated ability to swallow 2 tablets of the size and configuration of study drug
- •Anti-candidal prophylaxis of the oropharynx
- •If female and of childbearing potential, willing to use contraception
- •Ability to read, understand, and sign informed consent
排除标准
- •Skin GVHD other than a slowly evolving skin rash that involves ≤50% of body surface
- •Liver GVHD with total serum bilirubin >3 mg/dL
- •Negative intestinal biopsy for GVHD
- •Systemic prescription corticosteroid use within 30 days
- •Persistent vomiting of oral intake the precludes ingestion of study drug tablets
- •Multiorgan failure
- •Infection of the mouth or esophagus with a fungal organism
- •Known HIV seropositivity
- •Pregnancy or lactation
- •Previous use of BDP tablets, capsules, or inhalation products
- •Use of any investigational drug, biologic, or device within 30 days
- •Inability to comply with study procedures and scheduled study visits
结局指标
主要结局
Treatment failure (that is, flares of GVHD requiring immunosuppressive drug therapy) at study day 50.
次要结局
- Treatment failure at study day 80.
- Survival at transplant day 200.
- Adverse events.