Randomized, Exploratory and Prospective Phase I/II Clinical Trial to Evaluate the Safety and Efficacy of the Transfusion of Autologous Treg Cells Obtained From Thymic Tissue in the Prevention of Rejection in Heart Transplant Children
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 11
- 试验地点
- 2
- 主要终点
- Repopulation of Treg cells in the patient, determined as the increase of Treg values in peripheral blood with respect to pre-transplant values or in comparison with a control cohort of non-treated patients.
研究概览
简要总结
The investigators developed a protocol to isolate Treg cells from thymic tissue (thyTreg) discarded in pediatric cardiac surgeries. After completing the pre-clinical studies, the investigators have initiated a phase I/II clinical trial to test the safety and efficacy of the adoptive transfer of autologous thyTreg to prevent rejection in heart transplant children.
Condition or disease: Heart Transplantation Intervention/treatment: Regulatory T Cell (Treg) Infusion
详细描述
Current transplant practice is far from guaranteeing the life expectancy of patients, particularly if the patients are children. THYTECH aims to revolutionize the field of clinical immunology developing a new approach to govern the regulatory skills of immune system, preventing graft rejection and opening a new frontier in the treatment of immune diseases.
Transfer of regulatory T cells (Treg) has acquired growing interest in the race to achieve indefinite transplant survival. Up to now, the use of Treg therapy to prevent solid graft rejection in humans has demonstrated that this therapy is safe, but the clinical efficacy is limited. The small Treg numbers that can be purified from peripheral blood along with the low survival and limited suppressive capacity of differentiated Tregs obtained from adults have probably compromised the efficacy of this therapy.
The investigators have developed an innovative approach to overcome current barriers and make Treg transfer a reality equipped to achieve indefinite graft survival. The major innovation of THYTECH is the employment of thymic tissue, the site of Treg generation, as a new source of Tregs to obtain massive amounts of thymus-derived Tregs (thyTreg) with very high purity (>95% of CD 25+ Foxp3+ cells) and improved survival and suppressive capacities. The investigators are recruiting patients in a clinical trial transferring autologous Tregs in heart-transplanted children to prevent graft rejection.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- — 至 2 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient under two years of age, who meets all the necessary requirements to undergo a heart transplant.
- •Patients without contraindication to immunosuppressive drugs.
- •Parents and/or guardians must be willing and able to understand the purpose and risks of the study and must sign the informed consent document
排除标准
- •Patients with DiGeorge Syndrome, since their thymic function is affected.
- •Human immunodeficiency virus positive serology
- •Epstein-Barr virus active infection
- •Patients hyperimmunized with cytotoxic anti-human leukocyte antigen antibodies
- •Patients with a history of previous malignancy
- •Patients who have participated in other intervention studies in the last month.
- •Patients who have received induction therapy with Basiliximab or Thymoglobulin.
- •Patients who have previously been thymectomized or transplanted.
- •Patients who have been diagnosed with severe autoimmune disease (celiac disease, autoimmune hypothyroidism, autoimmune diabetes)
- •Patients who will receive an asystole heart
研究组 & 干预措施
10.000.000 thyTreg /kg
Autologous thyTreg 10.000.000
干预措施: Autologous thyTreg (Biological)
20.000.000 thyTreg /kg
Autologous thyTreg 20.000.000
干预措施: Autologous thyTreg (Biological)
结局指标
主要结局
Repopulation of Treg cells in the patient, determined as the increase of Treg values in peripheral blood with respect to pre-transplant values or in comparison with a control cohort of non-treated patients.
时间窗: 24 months
次要结局
- Incidence of episodes of acute myocardial rejection (diagnosed by echocardiography) that require treatment in the 2 years post-transplant(24 months)
- Change in the number of naive and memory Treg cells, and the production/levels of interferon gamma and interleukins (IL-4, IL-17A and IL-10).(24 months)
- Number of Treg cells in peripheral blood(24 months)
- Change on parameters of electrocardiogram (PR, QRS and corrected QT interval) of transplanted heart.(24 months)
- Overall patient survival rate at 24 months.(24 months)
- Change on parameters of echocardiogram (mitral and tricuspid regurgitation; mitral and tissue mitral Doppler; and tricuspid and tissue tricuspid Doppler ) of transplanted heart.(24 months)
- Decrease of cell subsets related with rejection (CD8 T cells subsets, activated T cells, antibody-secreting B cells) during the post-transplant follow-up period.(24 months)
- Number of participants with treatment-related adverse events as assessed by NCI-CTCAE V4.03 criteria.(24 months)
研究者
Rafael Correa-Rocha
Group Leader
Hospital General Universitario Gregorio Marañon