Treatment of Steroid Non-responsive Acute GVHD With Alpha 1 Antitrypsin (AAT). A Phase I/II Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Number (Percentage) of Patients at Each Dosing Cohort Who Experience no Toxicity and in Whom Graft Versus Host Disease (GVHD) is Stable or Improved
研究概览
简要总结
This phase I/II trial evaluates the efficacy and adverse effects of alpha 1 anti-trypsin (AAT) for the treatment of acute graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation.
详细描述
PRIMARY OBJECTIVES:
I. Determine the safety and tolerability of AAT in patients with steroid non-responsive acute GVHD.
II. Characterize pharmacodynamic effects of AAT on pro-inflammatory cytokines, heparan sulfate, and the spectrum of peripheral blood T cells.
III. Determine clinical responses of GVHD to AAT in patients with steroid non-responsive acute GVHD.
OUTLINE: This is a phase I/II dose-escalation study of AAT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Patients transplanted from related or unrelated, human leukocyte antigen (HLA) matched or mismatched donors
- •Patients transplanted with hematopoietic stem cells from any source
- •Patients receiving calcineurin inhibitors as part of graft versus host disease (GVHD) prophylaxis
- •Patients with acute GVHD grades II-IV developing despite GVHD prophylaxis
- •Patients who have not shown a satisfactory response to methylprednisolone-equivalent doses at 2 mg/kg/day, based on adjusted body weight
- •Signed and dated informed consent
排除标准
- •Patients who have received any systemic agents in addition to steroids for treatment of GVHD
- •Patients unable to give informed consent
- •Patients with manifestations of classic chronic GVHD
- •Patients with evidence of recurrent malignancy
- •Patients with acute/chronic GVHD overlap syndrome
- •Patients whose GVHD developed after donor lymphocyte infusion (DLI)
- •Patients with severe organ dysfunction, defined as
- •On dialysis
- •Requiring oxygen (O2) at more than 2 l/min
- •Uncontrolled arrhythmia or heart failure
- •Veno-occlusive disease (sinusoidal obstruction syndrome)
- •Patients with uncontrolled infections
研究组 & 干预措施
Cohort 1 (30 mg/kg)
Alpha 1 anti-trypsin (AAT) will be administered intravenously at a dose of 90 mg/kg (loading dose) on day 1 followed by 30mg/kg (maintenance dose) every other day (QOD) on days 3, 5, 7, 9, 11, 13 & 15.
干预措施: Alpha 1-Proteinase Inhibitor, Human 1 MG [Glassia] (Drug)
Cohort 2 (60 mg/kg)
AAT will be administered intravenously at a dose of 90 mg/kg (loading dose) on day 1 followed by 60 mg/kg (maintenance dose) QOD on days 3, 5, 7, 9, 11, 13 & 15.
干预措施: Alpha 1-Proteinase Inhibitor, Human 1 MG [Glassia] (Drug)
Cohort 3 (90 mg/kg)
AAT will be administered intravenously at a dose of 90 mg/kg on days 1, 3, 5, 7, 9, 11, 13 & 15.
干预措施: Alpha 1-Proteinase Inhibitor, Human 1 MG [Glassia] (Drug)
结局指标
主要结局
Number (Percentage) of Patients at Each Dosing Cohort Who Experience no Toxicity and in Whom Graft Versus Host Disease (GVHD) is Stable or Improved
时间窗: Adverse events were reported through 15 days after the last dose of AAT. GVHD response assessed at study day 28.
Toxicity and adverse events were assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. All adverse events were reported regardless of attribution to alpha 1 anti-trypsin (AAT). GVHD response was defined per standard criteria for improvement, no change or progression of signs/symptoms in skin rash (% body surface area), GI (nausea, vomiting, anorexia, diarrhea, GI bleeding, abdominal cramping) and hepatic function (serum bilirubin levels). For this outcome measure, the requirement for additional GVHD treatment beyond AAT was not included in the criteria for response (i.e patients who may have required additional GVHD treatment before study day 28 were not automatically categorized as non-responders or as having progressive GVHD).
次要结局
- Number (Percentage) of Patients at Each Dosing Cohort Who Experience One or More Thrombotic or Thrombo-embolic Events(Events were reported through 15 days after the last dose of AAT.)
- Number (Percentage) of Patients at Each Dosing Cohort With Occurrence of Infections(Infections were reported through 15 days after the last dose of AAT.)
- Number (Percentage) of Patients at Each Dosing Cohort Experiencing an Unexpected Serious Adverse Event (SAE)(SAEs were reported through 30 days after the last dose of alpha 1 anti-trypsin (AAT).)
- Number (Percentage) of Patients at Each Dosing Cohort Who Experience One or More Suspected Serious Adverse Reactions (Infusion Related Reactions)(Within 48 hours after each infusion)
- Number (Percentage) of Patients at Each Dosing Cohort With Progression of GVHD(GVHD responses were assessed on day 28 after starting AAT therapy or at time of death if patient died before study day 28.)