A Phase II, Randomized Study to Evaluate the Safety and Efficacy of Ex-Vivo Cultured Allogenic Mesenchymal Stem Cells For the Treatment of Extensive Chronic Graft Versus Host Disease
试验速览
- 阶段
- 2 期
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- The total Response rate defined as patients with complete and partial response.
研究概览
简要总结
Study Design: Treatment, Randomized, Open Label, Parallel Assignment,Safety/Efficacy Study.
The purpose of this study is to evaluate the safety and efficacy of mesenchymal stem cells (MSC) expanded ex-vivo infusion for the treatment of patients who have developed a newly diagnosed extensive or refractory chronic graft versus host disease (chronic GVHD) to the usual therapeutic measures.
详细描述
Chronic graft-versus-host disease (GVHD) is one of the main limitations to successful allogeneic hematopoietic stem cell transplantation (HSCT), and has a substantial impact not only on survival but also on the quality of life of otherwise cancer-free patients. Half of the patients undergoing a HLA-identical allografts who survive beyond 100 days may require long-term immunosuppressive treatment for extensive chronic GVHD, often for more than 2 years. More than one-third of patients with chronic GVHD do not respond to first-line therapy, which often involves combinations of corticosteroids and a calcineurin inhibitor. There is no standard second-line or salvage therapy for these patients and they have a poor outcome.
Mesenchymal stem cells (MSCs) are multipotent non-hematopoietic stem cells that can differentiate into various lineages and have been used to repair injured tissues. Recently, MSCs have also shown unique immunomodulatory properties ex-vivo, including inhibition of T-cell proliferation after stimulation by allo-antigens and mitogens, and prevention of the activity of cytotoxic T cells.MSCs have been used for the prophylaxis of acute GVHD and for the treatment of patients with steroid-refractory acute GVHD,but rarely have been used for extensive chronic GVHD.
Development of new therapeutic agents and strategies to rescue patients with extensive chronic GVHD would provide a significant benefit in an area of unmet medical need.
In this study, a single center randomized, non blinded Phase II clinical trial is proposed to study the safety and efficacy of mesenchymal stem cells (MSC) in the management of extensive chronic GVHD newly or refractory to the usual therapeutic measures.
Expanded MSC will be infused at a dose of 2 million cells/kg twice a week for 2 weeks and weekly for the following two weeks (six doses totally)in patients based first-line therapy (steroid plus cyclosporin A ) or their primary immunosuppressive therapies.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent obtained from patient and donor.
- •Any patient who has undergone allogeneic stem cell transplantation with extensive chronic GVHD.
- •Have not received additional agent for cGVHD within 3 months.
- •Expected life is more than 90 days.
- •Adequate pulmonary function with no evidence of chronic obstructive or severe restrictive pulmonary disease.
- •Adequate cardiac function with no evidence of uncontrolled high blood pressure,congestive heart failure, angina pectoris, acute myocardial infarction within 6 months prior to the process.
排除标准
- •Invasive fungal disease.
- •Active cytomegalovirus (CMV)/Epstein-Barr virus(EBV)/varicella disease).
- •Patient is with a history of hypersensitivity to bovine products.
- •Relapsed malignancy.
研究组 & 干预措施
Control group
Patients with newly diagnosed extensive cGVHD receive prednisone and cyclosporine or tacrolimus.
Patients with refractory extensive cGVHD receive primary treatment (eg,prednisone and cyclosporine or tacrolimus, or plus mycophenolate mofetil, or methotrexate.)
干预措施: Prednisone and cyclosporine or primary therapies (Drug)
Mesenchymal stem cell (MSC)
Patients with newly diagnosed extensive cGVHD receive MSC plus prednisone and cyclosporine or tacrolimus.
Patients with refractory extensive cGVHD receive MSC plus their primary immunosuppressive treatment (eg. prednisone + cyclosporine or tacrolimus, or plus mycophenolate mofetil, or plus methotrexate.)
干预措施: Mesenchymal stem cell (MSC) (Biological)
结局指标
主要结局
The total Response rate defined as patients with complete and partial response.
时间窗: Within the first 3 months (plus or minus 7 days) after randomization
次要结局
- Events Free Survival(Randomization until death or two years post last subject last treatment visit (or clinical cutoff))
- The percentage of patients who can taper or discontinue the immunosuppressive agents(Randomization untill two years post the last subject last treatment visit (or clinical cutoff))
- Overall Survival(Randomization until death or two years post last subject last treatment visit (or clinical cutoff))
- Serum cytokine levels and lymphocyte subsets in patients with chronic GVHD(Achieve best response within the first 3 months after randomization)