Infusion of Mesenchymal Stem Cells as Treatment for Steroid-Resistant Grade II to IV Acute GVHD or Poor Graft Function: a Multicenter Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 24
- 主要终点
- Arm 1. Efficacy of MSC infusion as treatment for steroid-resistant grade II - IV acute GVHD.
研究概览
简要总结
The present project aims at investigating the role of MSC for the treatment of patients with
Part 1: Steroid-refractory grade II-IV acute GVHD.
Part 2: Poor graft function (PGF)
Part 3: Low or falling donor T-cell chimerism after allogeneic HCT.
This is a multicenter phase II study examining the feasibility and efficacy of this approach.
详细描述
Part 1: complete recruitment Part 2: complete recruitment Part 3: recruiting
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patient eligibility criteria
- •Male or female of any age.
- •Previous allogeneic transplantation (related or unrelated donor, any degree of HLA matching) or autologous transplantation (for part 2 only) of HSC at any time before.
- •Any source of HSC (marrow, PBSC, cord blood) and any conditioning regimen.
- •Informed consent given by donor or his/her guardian if of minor age.
- •Additional criteria for each part of the protocol:
- •Part 1: MSC for steroid-refractory grade II-IV acute GVHD
- •Allogeneic transplantation.
- •Grade II-IV acute GVHD (see appendix A for acute GVHD grading) de novo or following DLI.
- •Acute GVHD refractory to mPDN 2 mg/kg/day or equivalent, defined as
- •progression of GVHD on day 3 after initiation of steroids
- •no improvement of GVHD on day 7 after initiation of steroids
- •absence of complete resolution of acute GVHD on day 14 after initiation of steroids
- •relapse of acute GVHD during or after steroid taper.
- •Ongoing therapy with Ciclosporine or Tacrolimus at therapeutic doses.
- •Patient may have received previously any other form of treatment for acute GVHD, but no new treatment started within 1 month of study entry.
- •Part 2: MSC for poor graft function (PGF)
- •Allogeneic or autologous transplantation.
- •Cytopenia in 2 or 3 lineages:
- •Hb < 8.0 g/dL and reticulocytes < 1%, with or without transfusion
- •Plt < 20,000/µL without transfusion
- •Neutrophils < 500/µL, without G-CSF administration
- •OR severe cytopenia in 1 lineage:
- •RBC transfusion dependent (if autologous transplantation; despite EPO administration if allogeneic transplantation)
- •Plt transfusion dependent
- •Neutrophils < 500/µL despite G-CSF administration
- •Cytopenia duration ≥ 2 weeks beyond day 28 after autologous HCT, or day 42 (day 60 for cord blood transplantation) after allogeneic HCT.
- •Cytopenia is not related to CMV or other infection, myelosuppressive/toxic drugs, renal failure, peripheral cell destruction or other identifiable cause.
- •In case of HLA-identical related donor and full donor chimerism, patient can only be included if a boost of donor CD34+ cells has been unsuccessful or is not feasible.
- •Part 3: MSC + DLI for poor donor T-cell chimerism
- •Nonmyeloablative allogeneic transplantation.
- •Donor T-cell chimerism < 50% for at least 2 consecutive weeks beyond day 21 after HCT OR
- •20% decrease in donor T-cell chimerism with the second value < 50%.
- •MSC donor inclusion criteria
- •Related to the recipient (sibling, parent or child) or unrelated.
- •Male or female.
- •Age > 16 yrs (no age limit if same as HSC donor).
- •No HLA matching required.
- •Fulfills generally accepted criteria for allogeneic HSC donation.
- •Informed consent given by donor or his/her guardian if of minor age.
排除标准
- •Patient exclusion criteria
- •HIV positive.
- •Active uncontrolled infection at time of scheduled MSC infusion.
- •Relapsing or progressing malignancy.
- •MSC donor exclusion criteria
- •HIV positive
- •Known allergy to Lidocaine
- •If donor other than HSC donor : any risk factor for transmissible infectious diseases.
研究组 & 干预措施
2
MSC infusion for poor graft function. In this arm, 2 x 10E6 MSC/Kg BW of the recipient will be injected during the first hour after thawing.
干预措施: Mesenchymal stem cells (Biological)
1
MSC infusion for steroid-refractory grade II-IV acute GVHD. In this arm, 4 x 10E6 MSC/Kg BW of the recipient will be injected during the first hour after thawing.
干预措施: Mesenchymal stem cells (Biological)
3
MSC + DLI for poor donor T-cell chimerism after allogeneic HCT. In this arm, 2 x 10E6 MSC/Kg BW of the recipient will be injected during the first hour after thawing.
干预措施: Mesenchymal stem cells (Biological)
结局指标
主要结局
Arm 1. Efficacy of MSC infusion as treatment for steroid-resistant grade II - IV acute GVHD.
时间窗: 30 days
Arm 2. Efficacy of MSC infusion as treatment for poor graft function
时间窗: 180 days
Arm 3. Efficacy of MSC infusion followed by donor lymphocyte infusion for preventing graft rejection in patients with low or failing donor T-cell chimerism after allogeneic HCT
时间窗: 180 days
次要结局
- Toxicity of MSC infusion(180 days)