Pancreatic Cancer
Conditions
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.
Interventions
BIOLOGICALCART-meso cells
CART-meso is a 2nd CAR, with mesothelin as target protein, 4-1BB as co- stimulator. The infusion will be scheduled to occur 3 (±1) days after a single dose of 1.5 grams/m\^2 of cyclophosphamide, which will be administered according to standard procedures, Thereby enhancing the efficacy of anti-tumor, reducing the potential of side effects.
Sponsors
The First Affiliated Hospital with Nanjing Medical University
Shenzhen BinDeBio Ltd.
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
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
China
Contacts
Primary ContactHongling ZHANG, PhD
Outcome results
None listed