Autologous Cytokine-Induced Killer Cell Transfusion in Combination With Gemcitabine Plus Cisplatin Regimen Chemotherapy for Metastatic Nasopharyngeal Carcinoma
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Complete remission (CR)
研究概览
简要总结
Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in Southern China and South Asia. After radiotherapy, some patients with nasopharyngeal carcinoma still had distant metastasis. In recent years, some chemotherapeutic agents, such as gemcitabine, cisplatin, were used to treat patients with advanced nasopharyngeal carcinoma, including those with local recurrence and distant metastases, with a certain short-term effect. However, chemotherapy alone is still not ideal for effectively improving the prognosis of patients with advanced nasopharyngeal carcinoma. Therefore, it is necessary to develop more-effective adjuvant therapies.
CIK cells (cytokine induced killer cells, CIK) are a population of heterogeneous cells generated by the in vitro amplification of mononuclear cells in peripheral blood. The cells are co-induced with multiple cytokines; the lymphocytes with co-expression of CD3+CD56+ have the strongest anti-tumor effect. Because of their non-MHC restricted tumor killing activity, CIK cells have a powerful anti-tumor effect both in vitro and in vivo, which spans a broad anti-tumor spectrum.
In this study, the patients with post-radiotherapy distant metastasis of NPC will be treated with autologous CIK cells in combination with Gemcitabine plus Cisplatin regimen chemotherapy(GC). The purpose of this study is to observe and evaluate the toxic side effects and the short- and long-term efficacy of CIK used in combination with GC chemotherapy to treat NPC in patients with distant metastasis after radiotherapy. Patients and Methods: 40 patients with distant metastasis after radiotherapy will accept 4 cycles chemotherapy of Gemcitabine plus cisplatin regimen and then are randomized divided into 2 groups. The 20 patients in GC+CIK group will be treated with maintaining therapy of adoptive autologous CIK cell transfusion sequentially; the other 20 patients will be followed-up only without CIK cells treatment. The safety of chemotherapy and CIK cells transfusion and the tumor regression status will be observed. The early response and long-term efficacy of two groups patients who accept GC chemotherapy or GC +CIK bio-therapy will be investigated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The primary lesions of all patients were classified as undifferentiated, non-keratinizing carcinoma at the initial stage for treatment (WHO, 1991 criteria) and no distant metastasis was observed based on imaging studies before radiotherapy ;
- •all patients had received standard doses of radiotherapy, were regularly followed-up after radiotherapy, and had distant metastatic lesions revealed by imaging studies;
- •metastases were found more than 6 months after the end of radiotherapy, with the expected survival time of more than 3 months;
- •in each case, no more than 10 metastatic lesions were found in the imaging studies;
- •Eastern Cooperative Oncology Group (ECOG) performance status was 0 - 1;
- •the bone marrow functioned normally (WBC > 4.0×109/L, Hb > 120 g/L, PLT > 100×109/L);
- •the ECG results were normal, and the liver and kidney were functional.
排除标准
- •Patients were excluded if they had central nervous system metastases;
- •uncontrolled infection; underlying disease that was severe or life-threatening;
- •the patients were pregnant or lactating;
- •ECOG perform status ≥ 2;
- •the patients who are suffering from auto immune diseases or patients who need to accept glucocorticoid treatment.
研究组 & 干预措施
GC chemotherapy plus CIK cells
A total of 40 patients enrolled will be accept 4 cycles GC chemotherapy(every 4 weeks),then they will randomized divided into two groups. 20 patients will maintain autologous CIK cells for 8 cycles (every 4 weeks); however,the other 20 patients will not accept CIK cells treatment. After the all 40 patients have accomplished 4 cycles GC regimen chemotherapy plus 8 cycles CIK cells treatment or 4 cycles GC chemotherapy alone, the early effects will be assessed and long-term efficacy such as OS and PFS will be evaluated.
干预措施: GC chemotherapy plus CIK cells (Gemcitabine, Cisplatin, Autologous CIK cells) (Drug)
GC chemotherapy
A total of 40 patients enrolled will be accept 4 cycles GC chemotherapy(every 4 weeks),then they will randomized divided into two groups. 20 patients will maintain autologous CIK cells for 8 cycles (every 4 weeks);the other 20 patients will not accept CIK cells treatment. After the all 40 patients have accomplished 4 cycles GC regimen chemotherapy plus CIK cells treatment or 4 cycles GC chemotherapy alone, the early effects will be assessed and long-term efficacy such as OS and PFS will be evaluated.
干预措施: GC chemotherapy (Gemcitabine, Cisplatin) (Drug)
结局指标
主要结局
Complete remission (CR)
时间窗: Participants will accept 4cycles GC regimen chemotherapy (every 4 weeks) plus 8 cycles CIK cells treatment (every 4 weeks), a total of therapy time will be 12 months.
(According to the response criteria in solid tumor(RECIST), version 1.1) Complete remission (CR):Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial remission (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study ; Progressive disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Partial remission (PR)
时间窗: Participants will accept 4cycles GC regimen chemotherapy (every 4 weeks) plus 8 cycles CIK cells treatment (every 4 weeks), a total of therapy time will be 12 months.
(According to the response criteria in solid tumor(RECIST), version 1.1) Complete remission (CR):Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial remission (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study ; Progressive disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Stable disease (SD)
时间窗: Participants will accept 4cycles GC regimen chemotherapy (every 4 weeks) plus 8 cycles CIK cells treatment (every 4 weeks), a total of therapy time will be 12 months.
(According to the response criteria in solid tumor(RECIST), version 1.1) Complete remission (CR):Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial remission (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study ; Progressive disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Progressive disease (PD)
时间窗: Participants will accept 4cycles GC regimen chemotherapy (every 4 weeks) plus 8 cycles CIK cells treatment (every 4 weeks), a total of therapy time will be 12 months.
(According to the response criteria in solid tumor(RECIST), version 1.1) Complete remission (CR):Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial remission (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study ; Progressive disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
次要结局
- overall survival time (OS)(Paticipants will be follow-up 2 years afer they have accomplished 4 cycles GC chemotharapy /or GC chemotharapy plus CIK cells treatment.)
- time to progression (TTP)(Paticipants will be follow-up 2 years afer they have accomplished 4 cycles GC chemotharapy /or GC chemotharapy plus CIK cells treatment.)
- progression free survival(PFS)(Paticipants will be follow-up 2 years afer they have accomplished 4 cycles GC chemotharapy /or GC chemotharapy plus CIK cells treatment.)
研究者
Jian-jun Li
Associate Professor
Sun Yat-sen University