A Multicenter, Open-label, Randomized, Phase I/II Clinical Trial Comparing Safety and Durable Overall Response Day 56 in Patients With Steroid Resistent Acute GvHD After Allogeneic Hematopoietic Stem Cell Transplant Treated With DSC or BAT
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 50
- 试验地点
- 10
- 主要终点
- Safety and tolerability evaluation including Severe Adverse Events (SAE).
研究概览
简要总结
A randomized (1:1) phase II open label study of DSC compared to Investigator choice Best Available Therapy (BAT) in allogeneic hematopoietic stem cell transplant recipients with Grades II-IV steroid refractory acute graft vs. host disease in the second part of the study. Patients will receive 2 doses of DSC. Additional doses (up to 4 doses) may be given depending on response.
No cross-over are planned in the second stage of the study.
详细描述
Main inclusion criteria:
Adult patients (age ≥ 18 years) with steroid refractory (SR) acute GvHD (aGVHD) grades II-IV after allo-HSCT.
Signed written study informed consent once SR-aGvHD is confirmed.
Main exclusion criteria:
Presence of an active uncontrolled infection requiring treatment. Has received systemic treatment for aGvHD apart from steroids. Clinical presentation resembling de novo chronic GvHD or GvHD overlap syndrome. Known human immunodeficiency virus infection (HIV). Patients suffering on active tuberculosis or viral hepatitis. Significant respiratory disease Presence of severely impaired renal function Patients with coagulopathy Pregnant or nursing (lactating) women Malignancy that has required treatment in the previous two years Any condition that would, in the Investigator's judgment, interfere with full participation in the study.
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
- 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
- •Adult patients (age ≥ 18 years) with steroid refractory acute GvHD grades II-IV after allo-HSCT.
- •Signed written study informed consent once SR-aGvHD is confirmed.
排除标准
- •Presence of an active uncontrolled infection including significant bacterial, fungal, viral or parasitic infection requiring treatment.
- •Has received systemic treatment for aGvHD apart from steroids.
- •Clinical presentation resembling de novo chronic GvHD or GvHD overlap syndrome.
- •Pregnant or lactating women.
- •Significant respiratory disease.
- •Presence of severely impaired renal function
- •Any corticosteroid therapy for indications other than aGvHD
- •Previous participation in a study of any investigational treatment agent within 30 days
- •Known human immunodeficiency virus infection (HIV).
- •Patients suffering on active tuberculosis or viral hepatitis
- •Significant respiratory disease
- •Presence of severely impaired renal or liver function
- •History of progressive multifocal leuko-encephalopathy
- •Patients with coagulopathy
- •History of severe chronic history of heart disease
- •Any condition that would, in the Investigator's judgment, interfere with full participation in the study.
研究组 & 干预措施
Best Available Treatment (BAT)
The BAT in this study will freely be identified by the Investigator prior to patient randomization and may include treatments such as: anti-thymocyte globulin (ATG), extracorporeal photopheresis (ECP), low-dose methotrexate (MTX), mycophenolate mofetil (MMF), mTOR inhibitors (everolimus or sirolimus), etanercept, vedolizumab, ruxolitinib or infliximab. Dose and frequency will depend on label (where approved) and institutional guidelines for various BAT.
干预措施: Best available Treatment (BAT) (Drug)
Decidua Stroma Cells (DSC)
Placenta derived decidua stroma cells (DSC). In the first phase I part, two different dose levels will be used, 1x10^6/kg and 3x10^6/kg. Two doses, one week apart, will be given. The decision to proceed to the next dose level will depend on results observed at the previous dose level.
The dose in the randomized part will be based on the findings in the phase I part. In the Phase II study all patients will receive 2 doses, one week apart. Depending on response, up to 6 doses in total may be given. Additional doses (beyond the first 2 doses) may be given one week apart until response.
干预措施: Decidua Stroma Cells (DSC) (Biological)
结局指标
主要结局
Safety and tolerability evaluation including Severe Adverse Events (SAE).
时间窗: 5 years
Adverse events will be assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Durable Response to treatment
时间窗: 56 days
Durable Overall Response (DOR) day 56.
次要结局
- Incidence of Relapse(5 year)
- Number of patients with overall response (CR+PR) at day 28(28 days)
- Change of Quality of Life(1 year)
- Incidence of Non-Relapse Mortality (NRM)(1 year)
- Incidence of secondary malignancies(5 year)
- Rate of Survival(1 year)
- Incidence of infections(1 year)
- Incidence of chronic GVHD(5 year)
研究者
Mats Remberger
Professor
Uppsala University Hospital