Mesothelin Positive Tumors
Conditions
Brief summary
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.
Interventions
BIOLOGICALanti-mesothelin CAR T cells
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%).
Sponsors
Marino Biotechnology Co., Ltd.
China Meitan General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. patients with mesothelin positive, recurrent or metastatic malignant tumors , including but not limited to pancreatic adenocarcinoma, ovarian cancer, or pleural mesothelioma. 2. relapsed or metastatic after standard treatment 3. measurable tumors by RECIST1.1 standard 4. patients are 18 to 70 years old. 5. life expectancy \> 3months. 6. KPS ≥70. 7. 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 . 8. Blood: Hgb ≥ 80 g/L, ANC ≥ 1×10\^9/L, PLT ≥ 50×10\^9/L. 9. 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
1. patients with a prior history of autoimmune disease or other diseases who need long-term use of systemic hormone drug or immunosuppressive therapy 2. active infection. 3. HIV positive. 4. active hepatitis B virus infection or hepatitis C virus infection. 5. currently enrolled in other study. 6. patients, in the opinion of investigators, may not be eligible or are not able to comply with the study. 7. patients who have allergic disease, or are allergic to T cell products or other biological agents used in the study. 8. patients whose tumors have metastasized to bone marrow, or have clinical signs of bone metastasis, such as bone and joint pain . 9. patients who have brain metastasis or signs of brain metastasis, such as loss of self-consciousness.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 2 years | incidents of treatment related adverse events per NCI CTCAE V4.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| progression free survival | 6 months | — |
| overall survival | 2 years | — |
| treatment response rate of anti-mesothelin CAR T cells | 4 weeks | 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). |
| activation of anti-mesothelin CAR T cells in patients | 6 months | measured by blood cytokine levels after CAR T cell infusion |
| persistence of anti-mesothelin CAR T cells in patients | 1 year | measured by quantitative PCR and flow cytometry |
| proliferation of anti-mesothelin CAR T cells in patients | 6 months | measured by quantitative PCR and flow cytometry |
Countries
China
Contacts
Primary ContactShidong Wei, MD
Outcome results
None listed