A Phase I Study of Adoptive Immunotherapy With Autologous Tumor Infiltrating Lymphocytes in Solid Tumors
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- • the safety and tolerability of autologous tumor infiltrating lymphocytes (TIL) in combination with Interleukin-2(IL-2) in patients with nasopharyngeal carcinoma (NPC).
研究概览
简要总结
Background: T cell based adoptive immunotherapy including CTL and TIL may stimulated the immune system and stop cancer cells from growing.
Objective: Phase I clinical trial to investigate the toxicity and immune response of therapy with autologous tumor infiltrating lymphocytes as adjuvant treatment for metastatic nasopharyngeal carcinoma and hepatocellular carcinoma after primary operation, radiotherapy and chemotherapy.
Methodology: Phase I clinical trial in patients with advanced nasopharyngeal carcinoma, hepatocellular carcinoma, breast cancer and other solid cancers. The investigators isolated lymphocytes from fresh tumor tissues, activated and expanded TILs in vitro; and infused the enough number (10e9 to 10e10) of TIL back patients.
详细描述
Tumor infiltrating lymphocytes were isolated from tumor tissues from tumor biopsy or operation. These TILs were cultured in human IL-2 medium for 2 to 3 weeks, and reactivated by OKT3, irradiated feeder cells from the PBMCs of healthy donors and LCL set from EBV-transformed normal B cells, and expanded in human IL-2 medium for another 15 days. 10e9 to 10e10 TILs were yielded. The phenotype, function and sterile were detected before these TILs infused patients. After accepting operation or first round of routine chemotherapy and radiotherapy, the patients were treated with autologous TILs 10e9-10e10 via intravenous in 30 min, q weekX2 weeks, and followed by two weeks with daily sc low-dose interleukine-2.
Patients will be evaluated for toxicity and immune response. Peripheral blood of patients using multimer analysis and/or ELISPOT assays. Additional, we will be able to determine anti-tumor effects from immunotherapy by evaluating the clinical response of patients with stable or progressive disease at the time of TILs infusion. Lastly, we will assess additional tumor markers in patients with relapsed/refractory disease by immunohistochemical staining of tumor sections from previous diagnostic or therapeutic biopsy samples to determine the incidence of additional tumor antigen targets that may be used in future studies.
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
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with nasopharyngeal carcinoma in stage IVa or Ivb and patients with metastatic hepatocellular carcinoma were planned for tumor biopsy or primary surgeon
- •Age 18 to 70 years.
- •Willing to sign a durable power of attorney
- •Able to understand and sign the Informed Consent Document
- •Life expectancy of greater than three months
- •Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for up to four months after receiving the preparative regimen.
- •Serology:
- •Seronegative for HIV antibody.
- •Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.
- •Hematology:
- •WBC (> 3000/mm(3)).
- •Platelet count greater than 100,000/mm.
- •Hemoglobin greater than 8.0 g/dl.
- •Chemistry:
- •Serum ALT/AST less or equal to 2.5 times the upper limit of normal.
- •Serum creatinine less than or equal to 1.6 mg/dl.
- •Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.
排除标准
- •Previous treatment with IL-
- •Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
- •Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
- •Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
- •Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
- •Concurrent systemic steroid therapy.
结局指标
主要结局
• the safety and tolerability of autologous tumor infiltrating lymphocytes (TIL) in combination with Interleukin-2(IL-2) in patients with nasopharyngeal carcinoma (NPC).
时间窗: {Time Frame: 12 months}
Twenty of participants with adverse events as a measure of safety and tolerability according to standard NIH criteria including fever, mucositis, dermatitis, vomiting and hematologic toxicity leucopenia, neutropenia and lymphocytoponia etc. and a Quality of Life assessment. Adverse events will be reported on the case report form. The problility of observing at least one subject experience an adverse event in a sample of 20 subjects is 0.99, if the probability of the event occurring is assumed to be 0.2. There will be 95% power to detect a change in the proportion of adverse events in the group from 0 before treatment to 0.2 after treatment.
次要结局
- • immune efficacy and anti-tumor effects of autologous tumor infiltrating lymphocytes (TIL) in combination with Interleukin-2(IL-2) in patients with nasopharyngeal carcinoma (NPC).([ Time Frame: 12 Months])
研究者
Jiang Li
Sun yat-sen University cancer center, biotherapy center
Sun Yat-sen University