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Intrahepatic cholangiocarcinoma (ICC) is one of the most common liver malignancies. Surgical treatment is the first choice. However, for patients without surgical indications, the benefits of conventional chemoradiotherapy are limited. CART is one of the fastest developed treatments in recent years. MUC-1 CART can target abnormal glycosylation of MUC-1 and then killing tumor specifically. Here, investigators intend to evaluate the safety and efficacy of MUC-1 CART in intrahepatic cholangiocarcinoma.
Investigators chose MUC-1 positive intrahepatic cholangiocarcinoma patients with one measurable lesion at least. After general assessment, MUC-1 CART treatment was given to the participants. Objective remission rate, disease control rate, duration of overall response, progression-free survival, overall survival, drugs related side effects and other endpoints events were recorded and analyzed, to assess the MUC-1 CART could or couldn't effectively control the progress of intrahepatic cholangiocarcinoma.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MUC-1 CART | Experimental | Patients are given fludarabine and cyclophosphamide as pretreatment before MUC-1 CART immunotherapy. After treatment, specific antibodies, CART cells and serum levels of cytokines will be assessed. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MUC-1 CART cell immunotherapy | Biological | After fludarabine and cyclophosphamide pre-chemotherapy,MUC-1 CART immunotherapy is given. A decent interval later, levels of specific antibodies, CART cells and serum cytokines will be assessed. |
| Measure | Description | Time Frame |
|---|---|---|
| Disease control rate | Percentage of patients whose cancer doesn't progress after treatment | Up to approximately 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Objective response rate | Percentage of patients whose cancer shrinks or disappears after treatment | Up to approximately 12 months |
| Duration of overall response | The time of initial response until documented tumor progression. |
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Inclusion Criteria:
1) ECOG physical fitness score was 0~1 or KPS score >70. 2) Routine blood tests were in accordance with the following criteria: HB (>90 g/L) (no blood transfusion within 14 days), ANC (>1.5 x10^9/L), PLT (> 80 x10^9/L), lymphocyte (> 0.7 x10^9/L), LY (> 15%), Alb (> 2.8 g/dL), serum lipase and amylase < 1.5^ULN (upper limit of normal value).
3) Biochemical examination should meet the following criteria: TBIL < 1.5x ULN (upper limit of normal value); ALT < 2.5 xULN; serum Cr<1 xULN; endogenous creatinine clearance > 50ml/min (Cockcroft-Gault formula).
4) Cardiac ejection fraction >55%. 8. No active hemorrhagic disease or severe coagulation dysfunction. 9. No allergy to the contrast media. 10. Women of childbearing age must undergo a pregnancy test (serum or urine) within 7 days before enrollment, and the results are negative, and are willing to use appropriate contraception methods during the experiment and 8 weeks after the last CART.
11. The volunteers voluntarily joined the study, signed informed consent, and had good compliance and follow-up.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Tingbo Liang, MD PhD | Contact | 8613666676128 | liangtingbo@zju.edu.cn | |
| Qi Zhang, MD | Contact | 8613819137113 | zhangqi86@gmail.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The second affiliated hospital of Zhejiang University | Recruiting | Hangzhou | Zhejiang | 310009 | China |
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| ID | Term |
|---|---|
| D018281 | Cholangiocarcinoma |
| C536137 | Medullary cystic kidney disease 1 |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
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| Up to approximately 12 months |
| Progression-free survival | The percentage of people does not get worse for a period of time after diagnosis | Up to approximately 12 months |
| Overall survival | The percentage of people still alive for a given period of time after diagnosis | Up to approximately 12 months |
| Common Toxicity Criteria for Adverse Effects | According to Common Toxicity Criteria for Adverse Effects version 4 | Up to approximately 12 months |
| EORTC QLQ - PAN26 | Assessed by the European Organization for Research and Treatment of Cancer Quality of Life | Up to approximately 12 months |
| Anti-MUC1 CART cell antibody | Serum level of anti-MUC1 CART cell antibody | Up to approximately 12 months |
| MUC1 CART cell | Serum level of MUC-1 CART cell | Up to approximately 12 months |
| Related cytokine | Serum level of related cytokine(like IL-2、IL-6、TNF-α、IFNγ and so on) | Up to approximately 12 months |
| D009369 | Neoplasms |