胰管腺癌或膽管癌第二期或第三期手術後的病人

主要目的： Dose-finding Phase I Part ●To assess the clinical safety/tolerability profile of escalating doses of Allogeneic Magicell-NK in PDA or cholangiocarcinoma patients post resection ●To assess the dose limiting toxicity (DLT) of Allogeneic Magicell-NK ●To determine the MTD/MFD of Allogeneic Magicell-NK Main Phase II part ●To evaluate the efficacy of Allogeneic Magicell-NK

溶液劑

Allogeneic NK cell

18A

100ML

第一期劑量探索試驗部分
● 評估安全性參數 (治療中不良事件 [TEAE]、實驗室檢驗數值、體重、生命徵象、劑量中斷/停止治療)
● 決定未來試驗的 DLT、MTD/MFD 及建議最終劑量
第二期試驗部分
● 無疾病存活期 (DFS)

受試者
1.在知情同意書上簽名及標記日期
2.性別不拘，簽署同意書時需年滿十八歲（含）以上
3.受試者原發腫瘤及殘餘原發腫瘤已經由肉眼切除手術切除，並根據國際抗癌聯盟（Union for International Cancer Control，簡稱UICC）組織病理學分期系統，滿足以下所有條件：
‐切除前或切除時，該腫瘤為II期或III期
‐局部殘餘腫瘤分類為切除邊緣乾淨 (R0) 或顯微鏡下切除邊緣陽性 (R1)
‐手術中腹腔灌洗後細胞學檢查呈陰性
4.經病理學確診為胰管腺癌或膽管癌
5.在篩選訪視前的12週內曾接受根治性切除手術，並即將接受輔助性SLOG化學療法
註：癌症患者無論有無接受前置式（手術前的）輔助性化學治療，進行手術後都可參與試驗
6.美國東岸癌症臨床研究合作組織（Eastern Cooperative Oncology Group，簡稱ECOG）體能狀態為0–1分
7.受試者在第1次訪視的檢測顯示具有足夠的血液學功能：
‐總白血球計數 ≥ 3,000細胞/立方公釐 (mm3)
‐絕對嗜中性球計數 ≥ 1,500細胞/立方公釐 (mm3)
‐血小板 ≥ 100,000計數/立方公釐 (mm3)
‐血紅素 ≥ 9 公克/分升 (g/dL)
‐凝血酶原時間之國際標準化比值於正常範圍內
註：在篩選期內可重複檢驗，以確認是否符合資格
8.受試者在第1次訪視的檢測顯示具有足夠的肝腎功能：
‐血清肌酸酐 ≤ 1.5倍正常值上限
‐血中尿素氨 ≤ 1.5倍正常值上限
‐總膽紅素 ≤ 1.5倍正常值上限
‐丙胺酸轉胺酶 (ALT) 及天門冬胺酸轉胺酶 (AST) ≤ 2.5倍正常值上限
‐鹼性磷酸酶 ≤ 5倍正常值上限
‐白蛋白 ≥ 3.0公克/分升 (g/dL)
註：在篩選期內可重複檢驗，以確認是否符合資格
9.人類免疫缺乏病毒（愛滋病毒）及梅毒螺旋體檢驗（快速血漿反應素試驗/性病研究實驗室試驗以及梅毒螺旋體血液凝集試驗）為陰性
10.曾感染過巨細胞病毒，即巨細胞病毒免疫球蛋白G檢測呈陽性
11.若有懷孕的可能，則必須同意使用至少兩種避孕措施，其中一種必須為保險套或其他適當的屏障法，持續的時間為
-自簽署知情同意至最後一劑試驗產品輸注完畢後28天內
-從oxaliplatin治療第一次給藥至最後一次給藥後至少15個月（女性）或12個月（男性）
-從gemcitabine治療第一次給藥至最後一次給藥後至少6個月（女性）或3個月（男性）
12.同意遵照試驗計畫書所訂定之治療
註：若有活動型B型肝炎，接受抗病毒治療是允許的

捐贈者
1.在知情同意書上簽名及標記日期
2.性別不拘，簽署同意書時需年滿十八歲（含）以上
3.在第一次訪視時的功能檢驗滿足以下所有條件：
具有足夠的血液學功能：
‐血紅素 ≥ 10 公克/分升 (g/dL)
‐血球容積比 ≥ 33%
‐總白血球計數 ≥ 4,000細胞/立方公釐 (mm3)
‐血小板 ≥ 100,000計數/立方公釐 (mm3)
‐淋巴球佔總體白血球比例 ≥ 25%
具有足夠的肝功能：
‐總膽紅素 < 2倍正常值上限
‐丙胺酸轉胺酶 (ALT) 和天門冬胺酸轉胺酶 (AST) ≤ 2.5倍正常值上限

Exclusion Criteria:

Received any other investigational, anti-neoplastic medications, or immune cell therapy within 28 days prior to screening visit.
Any prior history of malignant neoplasm, except:

Non-invasive, non-melanomatous skin cancer (including squamous cell carcinoma, basal cell carcinoma, or carcinoma in situ), curatively treated with cryosurgery or surgical excision only.
Other primary malignant neoplasm diagnosed as disease free for more than 5 years.
Immunocompromized, currently under immunosuppressive treatment for autoimmune disease, or have received systemic steroid of equivalent dosage higher than prednisolone 30 mg/day for more than 7 days within 14 days prior to Day 1.
With known metastases.
With ongoing acute diseases, or serious medical conditions within the past 2 years prior to screening, such as cardiovascular (e.g., New York Heart Association grade III or IV), hepatic (e.g., Child-Pugh Class C), psychiatric condition (e.g., alcoholism, drug abuse), medical history, physical findings, or laboratory abnormality that in the investigators' opinion could interfere with the results of the trial or adversely affect the safety of the subject.
Hypercoagulable state that may lead to clinically apparent thrombosis.
With known hypersensitivity to aminoglycoside (e.g., streptomycin, gentamicin) or bacitracin.
With known hypersensitivity to any of the components of Allogeneic Magicell-NK, including human serum albumin.
With known hypersensitivity to any of the components of S-1, leucovorin, oxaliplatin, or gemcitabine.
With any contraindication to S-1, leucovorin, oxaliplatin, or gemcitabine, including:

- Severe myelosuppression or myelosuppression that probably exacerbates.

With symptomatic CMV disease.
With any history of diagnosed or suspected cardiac arrhythmia or QT interval prolongation.
Male subject with a corrected QT interval (QTc) ≥ 450 ms and female subject with a QTc ≥ 470 ms as determined by electrocardiogram (ECG) examination at screening.
Received any drugs associated with QT prolongation within 28 days prior to the Screening Visit (refer to Appendix 3. Drugs Associated with QT Prolongation, including but not limited to the drug listed therein).
Received brivudine or its analogs (e.g., sorivudine) or any live vaccines within 28 days prior to the Screening Visit.
Female subject who is lactating or has positive serum or urine pregnancy test at screening.
Ages Eligible for Study