Phase I/II Multicenter Trial of Antigen-specific Cytotoxic T Cells in the Treatment of Opportunistic Infections
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Viral load change after Virus-CTL infusion
研究概览
简要总结
Epstein Barr Virus (EBV) or Cytomegalovirus (CMV) infection results in significant morbidity and mortality in hematopoietic stem cell transplantation (HSCT) patients. HSCT patients often face opportunistic infections due to the immunosuppressive state during transplantation. Antimicrobial drugs are usually used for prophylactic purposes and for treatment after early detectable infections. Unfortunately, some patients develop resistance to such drug treatment. In addition to HSCT patient, immune compromised patient may also be victim to opportunistic infections. Many infections can be effectively managed by functional immune recovery. In this study, the safety and efficacy of microbial-specific cytotoxic T lymphocytes (CTLs) will be investigated.
详细描述
Background:
Opportunistic infections are major causes of transplant-related morbidity and mortality in immunosuppressed patients, especially in the early post-transplant period. CMV, EBV, adenovirus (AdV), BK virus (BKV) and other viruses or non-viral pathogens may lead to life-threatening infections after transplantation.
Adoptive immunotherapy with cytotoxic T lymphocytes (CTLs) reactive with specific microbial antigens has proven to be effective without stimulating acute graft-versus-host disease (GVHD) owing to the significantly reduced nonspecific alloreactivity. This study aims to evaluate the safety and efficacy of treating opportunistic infections with microbial-specific CTLs in immune compromised patients.
Objective:
Primary study objectives: Infusion of autologous or allogenic pathogen-specific CTL to patients by I.V., to evaluate the safety.
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
- 6 Months 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects with or without hematopoietic stem cell transplantation / organ transplant recipients need to meet the following conditions:
- •Evidence of CMV, EBV, ADV, BKV or known pathogen infection (viral DNA, immunohistochemical cytology positive); contraindications or invalid to anti-microbial drugs.
- •Subjects with virus DNA increased in the 2 consecutive peripheral blood samples (≥ 1000 genomic copies/ml blood) at least 24 hours apart.
- •Initial hematopoietic reconstitution: neutrophils (ANC) ≥ 0.5x109 / L, platelet (PLT) ≥ 20x109 / L.
- •Patients with pahogen disease (organ/ tissue infiltration) symptoms, fever, diarrhea, or lymphadenopathy, regardless of the level of peripheral blood virus DNA, and confirmed by the presence of viral DNA or microbial antigens within body fluid or biopsy.
- •The subject / guardian has signed a written consent form before any trial begins.
- •Proper renal and hepatic functions (ULN denotes "upper limit of normal range"):
- •Creatinine ≤ 2*ULN.
- •Bilirubin ≤ 2*ULN.
- •SGOT ≤ 3*ULN.
- •SGPT≤ 3*ULN.
- •If CTL is not from the patient's own, then the provider of CTLs needs to meet the following criteria:
- •Did not receive chemotherapy or radiotherapy within 4 weeks prior to blood collection, and did not take any steroids for the previous week, did not use Penicillin or β-lactam antibiotics, or the lowest dose of other antibiotics.
- •White blood cells ≥ 3,500 / μl, lymphocytes ≥ 750 / μl.
- •Obtain a signed informed consent from the patient and / or the guardian or the donor of the BMT recipient.
- •Human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) or tuberculosis (TB) test is negative.
- •Physical examination in line with the standard of healthy blood donors.
排除标准
- •Subject infected with HCV (HCV antibody positive), HBV (HBsAg positive), HIV (HIV antibody positive), or HTLV (HTLV antibody positive).
- •GVHD (graft-versus-host disease) performance score at II-IV.
- •Subject is albumin-intolerant.
- •Subject with life expectancy less than 4 weeks.
- •Subject participated in other investigational somatic cell therapies within past 30 days.
- •Subject with positive pregnancy test result.
研究组 & 干预措施
Infusion of pathogen-specific CTLs
Repetitive CTL infusions to treat microbial infections
干预措施: pathogen-specific CTLs (Biological)
结局指标
主要结局
Viral load change after Virus-CTL infusion
时间窗: 2 months
The viral load response to the Virus-CTL infusion will be assessed by specific PCR of peripheral blood after infusion.
Using CTCAE 4 standard to evaluate the level of adverse events after receiving autologous or allogenic pathogen-specific CTL infusion
时间窗: 24 weeks
to evaluate the level of adverse events with CTCAE 4
次要结局
- The incidence of CTL infusion syndrome mimicking grade Ⅱ~Ⅳ GVHD within 30 days after the last dose of CTL infusion(1 months)
- Number of patients with chronic GVHD-like symptom(6 months)
- Reconstitution of anti-microbial immunity monitored by flow cytometry(6 months)
研究者
Lung-Ji Chang
President
Shenzhen Geno-Immune Medical Institute