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

Phase 1
Conditions
Mesothelin Positive Tumors
Interventions
Biological: anti-mesothelin CAR T cells
Registration Number
NCT02930993
Lead Sponsor
China Meitan General Hospital
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
20
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
anti-mesothelin CAR T cellsanti-mesothelin CAR T cellsDose 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 .
Primary Outcome Measures
NameTimeMethod
safety of infusion of autologous anti-mesothelin CAR T cells as assessed by the incidents of treatment related adverse events per NCI CTCAE V4.02 years

incidents of treatment related adverse events per NCI CTCAE V4.0

Secondary Outcome Measures
NameTimeMethod
activation of anti-mesothelin CAR T cells in patients6 months

measured by blood cytokine levels after CAR T cell infusion

persistence of anti-mesothelin CAR T cells in patients1 year

measured by quantitative PCR and flow cytometry

treatment response rate of anti-mesothelin CAR T cells4 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).

overall survival2 years
proliferation of anti-mesothelin CAR T cells in patients6 months

measured by quantitative PCR and flow cytometry

progression free survival6 months

Trial Locations

Locations (1)

China Meitan General Hospital

🇨🇳

Beijing, China

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