Phase II Study of Carboplatin and Docetaxel Followed by Epstein-Barr Virus Cytotoxic T Lymphocytes in Patients With Refractory/Relapsed EBV-positive Nasopharyngeal Carcinoma(CADEN)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 3
- 主要终点
- The primary endpoint of the study is to evaluate the overall response rate for patients with advanced-stage, relapsed/refractory, EBV positive nasopharyngeal carcinoma after re-induction chemotherapy and immunotherapy.
研究概览
简要总结
Patients have a type of cancer called nasopharyngeal carcinoma (NPC) that has either come back or not gone away after the best known standard treatments.
Most patients that respond to chemotherapy once their NPC tumors have come back have been treated with a platinum-based medication like cisplatin. However, since many patients are given cisplatin during their initial treatment for NPC, in this study, they will be treated with another platinum-based chemotherapy medicine that has been used in patients with NPC called carboplatin. In this study, carboplatin will be used in combination with another drug called docetaxel. Other studies in patients with advanced head and neck cancer have shown that docetaxel can cause tumors to respond better and allow patients to survive longer when added to the standard treatments for those diseases.
Some patients with NPC show evidence of infection with the virus that causes infectious mononucleosis, known as the Epstein Barr virus (EBV), before or at the time of their cancer diagnosis. EBV is found in the cancer cells of almost all patients with advanced stage disease, suggesting that it may play a role in causing NPC. Previously, patients have been treated with high-risk NPC using EBV-specific cytotoxic T cells. These cells are grown in the laboratory and taught to recognize and attack EBV infected cells. In the past, patients were either given the cells alone or just after they had received a medication to briefly lower their white blood cell count. In both cases, many patients had their tumors shrink and in some cases completely disappear after being treated with these EBV-specific cytotoxic T cells.
Investigators have now decided to look at how patients with NPC and their tumors respond to the treatment combination of chemotherapy and EBV-CTL. Patients are being asked to participate in this study since the NPC tumor is associated with EBV and has either come back or not responded to standard treatment. This combination of chemotherapy and EBV-CTLs is an investigational treatment not approved by the Food and Drug Administration.
The purpose of this study is to see how relapsed or refractory, EBV-associated NPC tumors respond when treated with carboplatin and docetaxel followed by EBV-CTL.
详细描述
A blood sample will be obtained to start making the CTLs before the patient begins chemotherapy. The patients EBV-specific T cells will be grown while the patient is being treated with chemotherapy and given back to the patient after their chemotherapy is completed.
To prepare the CTLs, 60-70 cc of blood will be taken from the patient. The amount of blood collected depends on their size and weight, no more than 3 cc of blood per kg of body weight will be collected at any one time.
This blood will be used to grow an EBV-infected B-cell line and then a T-cell line. B cells and T cells are types of white blood cells that help fight infections in the body. After growing T cells in the laboratory, these cells will be stimulated with EBV infected B cells. The B cells have been treated with radiation so they cannot grow; however, they can provide the stimulation that will train the T cells to recognize and kill EBV infected cells.
The generation of EBV-CTL requires the use of a special cell line, called lymphoblastoid cell line, which will be made from the blood by infecting cells with EBV. Once the LCLs are made, the T cells will be repeatedly stimulate with the LCLs to make EBV-CTL.
The CTLs will then be tested to make sure they kill the EBV infected cells before they are given back to the patient. If the number of CTLs produced is low, investigators may need to obtain additional blood samples to make these cells.
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
- 10 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Chemotherapy and Immunotherapy
- Docetaxel 60 mg/m2 IV on Day 1
- Carboplatin with target AUC of 5 (mg/ml x min) on Day 1
- Dexamethasone 5 mg/m2/dose (max of 8 mg/dose) po q hs on Day 0, and q am and hs on Day 1
- After cycle 1, subsequent cycles of chemotherapy may start once ANC > 1000 and platelets > 100,000 post nadir
- Up to an additional 2 cycles of chemotherapy, given per the above schedule, may be given if the EBV-specific cytotoxic T lymphocytes product is not available after the initial 4 cycles
干预措施: Docetaxel (Drug)
Chemotherapy and Immunotherapy
- Docetaxel 60 mg/m2 IV on Day 1
- Carboplatin with target AUC of 5 (mg/ml x min) on Day 1
- Dexamethasone 5 mg/m2/dose (max of 8 mg/dose) po q hs on Day 0, and q am and hs on Day 1
- After cycle 1, subsequent cycles of chemotherapy may start once ANC > 1000 and platelets > 100,000 post nadir
- Up to an additional 2 cycles of chemotherapy, given per the above schedule, may be given if the EBV-specific cytotoxic T lymphocytes product is not available after the initial 4 cycles
干预措施: Carboplatin (Drug)
Chemotherapy and Immunotherapy
- Docetaxel 60 mg/m2 IV on Day 1
- Carboplatin with target AUC of 5 (mg/ml x min) on Day 1
- Dexamethasone 5 mg/m2/dose (max of 8 mg/dose) po q hs on Day 0, and q am and hs on Day 1
- After cycle 1, subsequent cycles of chemotherapy may start once ANC > 1000 and platelets > 100,000 post nadir
- Up to an additional 2 cycles of chemotherapy, given per the above schedule, may be given if the EBV-specific cytotoxic T lymphocytes product is not available after the initial 4 cycles
干预措施: Dexamethasone (Drug)
Chemotherapy and Immunotherapy
- Docetaxel 60 mg/m2 IV on Day 1
- Carboplatin with target AUC of 5 (mg/ml x min) on Day 1
- Dexamethasone 5 mg/m2/dose (max of 8 mg/dose) po q hs on Day 0, and q am and hs on Day 1
- After cycle 1, subsequent cycles of chemotherapy may start once ANC > 1000 and platelets > 100,000 post nadir
- Up to an additional 2 cycles of chemotherapy, given per the above schedule, may be given if the EBV-specific cytotoxic T lymphocytes product is not available after the initial 4 cycles
干预措施: EBV-specific cytotoxic T lymphocytes (Biological)
Chemotherapy and Immunotherapy
- Docetaxel 60 mg/m2 IV on Day 1
- Carboplatin with target AUC of 5 (mg/ml x min) on Day 1
- Dexamethasone 5 mg/m2/dose (max of 8 mg/dose) po q hs on Day 0, and q am and hs on Day 1
- After cycle 1, subsequent cycles of chemotherapy may start once ANC > 1000 and platelets > 100,000 post nadir
- Up to an additional 2 cycles of chemotherapy, given per the above schedule, may be given if the EBV-specific cytotoxic T lymphocytes product is not available after the initial 4 cycles
干预措施: G-CSF or Peg-GCSF (Biological)
结局指标
主要结局
The primary endpoint of the study is to evaluate the overall response rate for patients with advanced-stage, relapsed/refractory, EBV positive nasopharyngeal carcinoma after re-induction chemotherapy and immunotherapy.
时间窗: 3 months
The overall response rate for patients with advanced-stage, relapsed/refractory, EBV positive nasopharyngeal carcinoma after re-induction chemotherapy (treatment with docetaxel and carboplatin) followed by immunotherapy with EBV-specific Cytotoxic T lymphocytes will be measured. Response rates will be estimated as the percent of patients whose best response is a CR or PR, and a 95% confidence interval will be calculated for the fraction of responses obtained.To measure the overall response rate, disease will be determined by imaging (MRI, CT, and/or PET imaging) 8 weeks after immunotherapy. In addition, per standard of care, disease re-evaluation will continue 3 months during the first year after participation and then as clinically indicated per the patient's primary oncologist.
次要结局
- Response to re-induction chemotherapy(8 weeks)
- Evaluation of immune response by measuring EBV-DNA levels(8 weeks)
研究者
Chrystal Louis
Assistant Professor Pediatrics-Hem-Onc Cell & Gene
Baylor College of Medicine