Study of Autologous T-cells in Patients With Metastatic Pancreatic Cancer
- Conditions
- Pancreatic Cancer
- Interventions
- Biological: CART-meso cells
- Registration Number
- NCT03638193
- Lead Sponsor
- Shenzhen BinDeBio Ltd.
- Brief Summary
This is a study in which pancreatic cancer patients receive a immunotherapy with CART-meso cells administered at 3 days after one dose of cyclophosphamide. CART-meso cells are patients' own T cells lentivirally transduced to express anti-mesothelin scFv fused to TCRζ and 4-1BB costimulatory domains.The lymphodepletion with cyclophosphamide may prolong the persistence of CART cells.
- Detailed Description
This study is being conducted to assess the safety and efficacy of immunotherapy with CART-meso cells in dose escalation design. The trial will begin in Cohort 1 and progress to Cohorts 2, depending upon dose limiting toxicity (DLT) assessment .
Subjects will be enrolled serially, but infusions will be staggered to allow assessment of DLTs for determination of cohort progression, expansion, or dose de-escalation.
Cohort 1 subjects will receive a single dose of 1-3x10\^7 /m\^2 lentiviral transduced CART-meso cells after conditioning chemotherapeutic regimen.
Cohort 2 subjects will receive a single dose of 1-3x10\^8 /m\^2 lentiviral transduced CART-meso cells cells after conditioning chemotherapeutic regimen.
Dose limiting toxicity is defined as any adverse reactions at level 3 or above that may be associated with CART-meso within 4 weeks after infusion.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 10
- Signed informed consent
- Unresectable or metastatic pancreatic cancer
- Persistent cancer after at least one prior standard of care chemotherapy for advanced stage disease
- 18 - 70 years of age
- ECOG performance status of 0 or 1
- Life expectancy greater than 3 months
- Satisfactory organ and bone marrow function
- Meets blood coagulation parameters
- Male and Female subjects of reproductive potential agree to use approved contraceptive methods
- Participation in a therapeutic investigational study within 4 weeks prior to the screening visit
- Anticipated need for systemic chemotherapy within 2 weeks before apheresis and infusion
- Active invasive cancer other than pancreatic cancer
- HIV, HCV, or HBV infections
- Active autoimmune disease requiring immunosuppressive therapy within 4 weeks prior to screening visit, with exception of thyroid replacement
- Ongoing or active infection
- Planned concurrent treatment with systemic high dose corticosteroids
- Patients requiring supplemental oxygen therapy
- Prior therapy with gene modified cells
- Previous experimental therapy with SS1 moiety, murine or chimeric antibodies
- History of allergy to murine proteins
- History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
- Clinically significant pericardial effusion, CHF, or cardiovascular condition that would preclude assessment of mesothelin induced pericarditis or that may worsen as a result of toxicities expected for this study
- Pregnant or breastfeeding women
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description CART-meso cells CART-meso cells A single dose of CART-meso T cells will be administered intravenously.The dose is 1-3×10\^7/m\^2 CART positive cells(chort 1)or 1-3×10\^8/m\^2 CART positive cells(chort 2).
- Primary Outcome Measures
Name Time Method Safety of CART-meso infusion: number of adverse events 60 months Number of Adverse Events evaluated with NCI CTC AE, version 4.0\[Safety evaluation\]
- Secondary Outcome Measures
Name Time Method Clinical response of CART-meso 60 months Number of patients with tumor response including overal remission ,complete ression,progression-free survival，progressive disease ,etc.
CAR-T cell detection 60 months Detection of transferred T cells in peripheral blood or bone marrow using multi-parameter flow cytometer.
Trial Locations
- Locations (1)
Nanjing First Hospital
🇨🇳Nanjing, Jiangsu, China