A Prospective Multicenter Open-label, Not Controlled Phase Ib-II Clinical Trial to Assess the Safety and Immunologic Efficacy of Virus-specific T Lymphocytes From the Best Donor in Receptors of Hematopoietic Progenitor Allogeneic Transplant
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 7
- 主要终点
- Safety assessment: Adverse events
研究概览
简要总结
Marrow transplanted immunocompromised patients with cytomegalovirus (CMV) viral infection will be treated with CMV activated T-Lymphocytes. T-Lymphocytes will be obtained through an apheresis from a compatible donor.
Safety and immunoreconstitution parameters in blood samples will be assessed up to +60 days after the treatment.
详细描述
A prospective, multicentre, open-label and uncontrolled phase Ib-II clinical trial in which a total of 20 patients ≥ 1 year of age with an allogeneic transplant of hematopoietic progenitors and post-transplant CMV infection will be included. The main objective is to evaluate the safety of the infusion of CMV activated T-lymphocytes and secondary objectives are to evaluate the efficacy through clinical evolution, viral load, ability to induce immunoreconstitution against the virus and evaluation of the persistence of specific T cells.
The treatment will be administered intravenously (central or peripheral route) in a single dose at a dose of 0.01-5 E4 specific virus T lymphocytes per Kg of receptor weight. After the infusion, patients will follow periodic controls (+7, +14, +21, +28, +45 and +60 days) in which a clinical evaluation will be performed and blood samples will be obtained in order to evaluate the persistence of specific T cells in the recipient:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Recipient of an allogeneic hematopoietic progenitors cell transplant (irrespectively of the donor source, donor type conditioning and underlying disease) that is beyond the day +30 of the procedure
- •Patient with post-transplant infection due to CMV refractory or resistant to optimal pharmacological treatment. Specifically, the patient must be included in any of the following cases
- •Patient with organic disease caused by CMV (confirmed by histology) resistant to antiviral first line treatment
- •Patient with CMV reactivation and no organic disease, resistant or intolerant to 2 previous antiviral treatment lines (ganciclovir/valganciclovir and foscarnet) or not candidate to be treated due to not acceptable expected toxicity (severe renal insufficiency, neutropenia or severe thrombopenia) It is agreed that the patient is affected with a resistant CMV infection if the CMV copies doesn't decrease in > 1 log in total blood or otherwise the absolute number of copies > 1x10E4/mL in total blood after 2 weeks of antiviral treatment.
- •Patients with reactivation of recurrent CMV despite correct anti-CMV treatment. It will be considered a recurrent CMV infection if the patient has > 2 reactivations in a period <6 months despite having received correct anti-CMV treatment
- •Documented genetic mutations associated with ganciclovir or foscarnet resistance
- •≥ 1 year of age
- •Estimated life expectancy > 30 days
- •Signature of the informed consent form
排除标准
- •Acute graft-versus-host disease (GVHD) ≥ grade II or chronic ≥ moderate
- •Corticosteroid ≥ 0.5mg/kg regardless the indication
- •Disease relapse at the time of infection or at any time after the Allogeneic transplant.
- •Severe renal disease (creatinine > 3gr/dL)
- •Severe hepatic disease (bilirubin >3mg/dL or aspartate aminotransferase (AST) >500 U/L) except if it is secondary to the viral infection.
- •Having received a donor lymphocytes infusion or any cell therapy product within 60 days prior to inclusion in the study (with the exception of transfusions), or having it planned within the next 60 days.
- •Alteration of the general condition, infection or clinical or hemodynamic instability that, in the opinion of the researcher, does not recommend the use of T cells
- •Known hypersensitivity to murine proteins or iron dextran.
- •Positive serology to human immunodeficiency virus (HIV), hepatitis B virus (HBV) (HBsAg, HBcAc), hepatitis C virus (HCV) and/or syphilis
- •Pregnant, lactating or women without adequate contraception
- •Participation in a clinical trial with investigational medicinal products the last 30 days
研究组 & 干预措施
Activated T-Lymphocytes
Allogeneic T-Lymphocytes obtained from apheresis activated against CMV.
干预措施: Activated T-Lymphocytes (Drug)
结局指标
主要结局
Safety assessment: Adverse events
时间窗: 60 days
Adverse events
次要结局
- Lymphocyte subpopulations(+7, +14, +28, +60 days)
- T-cell persistence by chimerism(+14, +28 days)
- IFN-γ+ spot forming cells(+7, +14, +28, +60 days)
- Polymerase chain reaction (PCR)(+7, +14, +21, +28, +45, +60 days)
- Time elapsed in identifying the donor(Day 0)