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Safety and Efficacy Evaluation of MUC-1 CART in the Treatment of Intrahepatic Cholangiocarcinoma

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ClinicalTrials.gov Identifier: NCT03633773
Recruitment Status : Recruiting
First Posted : August 16, 2018
Last Update Posted : August 22, 2018
Sponsor:
Information provided by (Responsible Party):
Second Affiliated Hospital, School of Medicine, Zhejiang University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Intrahepatic Cholangiocarcinoma Biological: MUC-1 CART cell immunotherapy Phase 1 Phase 2

Detailed Description:
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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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 9 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety and Efficacy Evaluation of MUC-1 CART in the Treatment of Intrahepatic Cholangiocarcinoma
Actual Study Start Date : July 1, 2018
Estimated Primary Completion Date : August 31, 2023
Estimated Study Completion Date : December 31, 2024


Arm Intervention/treatment
Experimental: MUC-1 CART
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.
Biological: MUC-1 CART cell immunotherapy
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.




Primary Outcome Measures :
  1. Disease control rate [ Time Frame: Up to approximately 12 months ]
    Percentage of patients whose cancer doesn't progress after treatment


Secondary Outcome Measures :
  1. Objective response rate [ Time Frame: Up to approximately 12 months ]
    Percentage of patients whose cancer shrinks or disappears after treatment

  2. Duration of overall response [ Time Frame: Up to approximately 12 months ]
    The time of initial response until documented tumor progression.

  3. Progression-free survival [ Time Frame: Up to approximately 12 months ]
    The percentage of people does not get worse for a period of time after diagnosis

  4. Overall survival [ Time Frame: Up to approximately 12 months ]
    The percentage of people still alive for a given period of time after diagnosis

  5. Common Toxicity Criteria for Adverse Effects [ Time Frame: Up to approximately 12 months ]
    According to Common Toxicity Criteria for Adverse Effects version 4

  6. EORTC QLQ - PAN26 [ Time Frame: Up to approximately 12 months ]
    Assessed by the European Organization for Research and Treatment of Cancer Quality of Life

  7. Anti-MUC1 CART cell antibody [ Time Frame: Up to approximately 12 months ]
    Serum level of anti-MUC1 CART cell antibody

  8. MUC1 CART cell [ Time Frame: Up to approximately 12 months ]
    Serum level of MUC-1 CART cell

  9. Related cytokine [ Time Frame: Up to approximately 12 months ]
    Serum level of related cytokine(like IL-2、IL-6、TNF-α、IFNγ and so on)



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 18-65 years old.
  2. The expression of ST glycosylated MUC-1 was more than 1+ in immunohistochemistry(IHC) by applicant-approved laboratory.
  3. Histopathology or cytology confirmed intrahepatic cholangiocarcinoma.
  4. Patients who are unable to perform surgery or are not suitable for surgery, or who have recurrence after surgery, or who are unwilling to undergo chemotherapy.
  5. With at least one extracranial measurable lesion according to RECIST 1.1 edition.
  6. The expected survival time is more than 60 days.
  7. The main organs are functional and meet the following 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:

  1. The transduction efficiency of T cells was <10% or T cells expanded less than 5 times after culture.
  2. Chimeric antigen receptor therapy or other transgenic T cell therapy.
  3. Pregnant or lactating women.
  4. In the first 4 weeks before the start of the study, they took part in other drug clinical trials.
  5. Patients with hypertension who can not be well controlled by a single antihypertensive drug (SBP> 140 mmHg, DBP> 90 mmHg), myocarditis or congenital heart disease, myocardial ischemia or infarction above grade I, arrhythmia above grade I (including QT interval < 440 ms) or cardiac insufficiency.
  6. Long term unhealed wounds or fractures.
  7. With a history of psychotropic substance abuse and unable to quit or have a history of mental disorders.
  8. Past and current objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, severe impairment of lung function, etc.
  9. With uncontrollable fungi, bacteria, viruses or other infections, or need antibacterial treatment. The presence of simple urinary tract infections and uncomplicated bacterial pharyngitis is allowed after consultation with a medical supervisor, if there is a response to active therapy.
  10. According to the NCI-CTCAE 4.0 standard, the patients who had used chemotherapy in the past had grade 2 hematological toxicity or grade 3 non-hematological toxicity.
  11. With a history of HIV or hepatitis B or hepatitis C virus infection.
  12. There are any indwelling catheters or drainage tubes (e.g. percutaneous nephrostomy, Frey's catheter, bile drainage or pleural/peritoneal/pericardial catheter). The use of dedicated central venous catheters is permitted.
  13. With brain metastases.
  14. With a history or disease of CNS, such as epileptic seizures, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving CNS.
  15. With a major immunodeficiency.
  16. The main therapeutic drugs in this study (including fludarabine, cyclophosphamide, sodium mesylate, tropizumab and anti-infective drugs used during pretreatment) had a history of severe hypersensitivity.
  17. In the first 6 months of admission, there was a history of deep venous thrombosis or pulmonary embolism.
  18. History of autoimmune diseases (e.g. Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) that cause terminal organ injury or require systemic immunosuppressive/systemic disease-regulating drugs.
  19. With any diseases that may interfere with the safety or efficacy of treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03633773


Contacts
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Contact: Tingbo Liang, MD PhD 8613666676128 liangtingbo@zju.edu.cn
Contact: Qi Zhang, MD 8613819137113 zhangqi86@gmail.com

Locations
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China, Zhejiang
The second affiliated hospital of Zhejiang University Recruiting
Hangzhou, Zhejiang, China, 310009
Contact: Qi Zhang, MD    8613819137113      
Sponsors and Collaborators
Second Affiliated Hospital, School of Medicine, Zhejiang University

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Responsible Party: Second Affiliated Hospital, School of Medicine, Zhejiang University
ClinicalTrials.gov Identifier: NCT03633773     History of Changes
Other Study ID Numbers: SAHZJU-Y2018-078
First Posted: August 16, 2018    Key Record Dates
Last Update Posted: August 22, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Second Affiliated Hospital, School of Medicine, Zhejiang University:
ICC
Mucin-1
CAR-T
Immunotherapy

Additional relevant MeSH terms:
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Cholangiocarcinoma
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Immunologic Factors
Physiological Effects of Drugs