Anti-mesothelin CAR T Cells for Patients With Recurrent or Metastatic Malignant Tumors

Study Overview
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Brief Summary
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This is a single-arm, open-label, one center, dose escalation clinical study, to determine the safety and efficacy of infusion of autologous T cells engineered to express chimeric antigen receptor targeting mesothelin in adult patients with mesothelin positive, recurrent or metastatic malignant tumors.

Official Title
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A Safety and Efficacy Study of Autologous T Cells Engineered to Express Chimeric Antigen Receptor Targeting Mesothelin in Patients With Recurred or Metastatic Malignant Tumors

Conditions
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Mesothelin Positive Tumors

Intervention / Treatment
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* Biological: anti-mesothelin CAR T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with mesothelin positive, recurrent or metastatic malignant tumors , including but not limited to pancreatic adenocarcinoma, ovarian cancer, or pleural mesothelioma. relapsed or metastatic after standard treatment measurable tumors by RECIST1.1 standard patients are 18 to 70 years old. life expectancy > 3months. KPS ≥70. satisfactory major organ functions: adequate heart function with LVEF≥50%; no obvious abnormities in ECG; pulse oximetry ≥ 90%; cockcroft-gault creatinine clearance≥40 ml/min; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3ULN; Bilirubin ≤2.0 mg/dl . Blood: Hgb ≥ 80 g/L, ANC ≥ 1×10^9/L, PLT ≥ 50×10^9/L. women of reproductive potential must have a negative pregnancy test. Male and female of reproductive potential must agree to use birth control during the study and one year post study. Exclusion Criteria: patients with a prior history of autoimmune disease or other diseases who need long-term use of systemic hormone drug or immunosuppressive therapy active infection. HIV positive. active hepatitis B virus infection or hepatitis C virus infection. currently enrolled in other study. patients, in the opinion of investigators, may not be eligible or are not able to comply with the study. patients who have allergic disease, or are allergic to T cell products or other biological agents used in the study. patients whose tumors have metastasized to bone marrow, or have clinical signs of bone metastasis, such as bone and joint pain . patients who have brain metastasis or signs of brain metastasis, such as loss of self-consciousness.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: anti-mesothelin CAR T cells<br>Dose escalation study aimed to assess the safety and efficacy of anti-mesothelin CAR T cells. CAR T dosage ranging from 5×10^4 /kg to 1×10^7 /kg will be tested . | Biological: anti-mesothelin CAR T cells<br>* Patients will be received a three-day regimen of chemotherapy consisting of cyclophosphamide aimed to deplete the lymphocytes. 1 to 4 days after lymphodepletion, patients are intravenously infused with anti-mesothelin CAR T cells in a three-day split-dose regimen (day0,10%; day1, 30%; day2, 60%).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety of infusion of autologous anti-mesothelin CAR T cells as assessed by the incidents of treatment related adverse events per NCI CTCAE V4.0 | incidents of treatment related adverse events per NCI CTCAE V4.0 | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| treatment response rate of anti-mesothelin CAR T cells | Defined as the overall response rate (ORR), the proportion of patients who achieved complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD) based on the response evaluation criteria in solid tumor version 1.1 (RECIST1.1). | 4 weeks | 
| progression free survival |  | 6 months | 
| overall survival |  | 2 years | 
| proliferation of anti-mesothelin CAR T cells in patients | measured by quantitative PCR and flow cytometry | 6 months | 
| activation of anti-mesothelin CAR T cells in patients | measured by blood cytokine levels after CAR T cell infusion | 6 months | 
| persistence of anti-mesothelin CAR T cells in patients | measured by quantitative PCR and flow cytometry | 1 year |