Pancreatic Cancer
Conditions
Keywords
Pancreatic Cancer, CAR / CART, T cells, Immunotherapy, Gene therapy, Redirected T cells, Autologous T cells
Brief summary
This is a study in which pancreatic cancer patients receive a combination therapy with CART-meso cells and CART19 cells administered at 3 days after one dose of cyclophosphamide. CART-meso cells are patients' own T cells that were modified in the laboratory to express a receptor specific to the mesothelin protein. CART19 cells are patients' own T cells that were modified in the laboratory to express a receptor specific to a protein called CD19. The CD19 protein is expressed on white blood B cells. CART19 cells are expected to attack the B cells and impede the antibody response against CART-meso cells. The investigators hypothesize that this combination therapy may prolong the duration of CART-meso cells in the body. Additionally, one dose of cyclophosphamide may enhance engraftment and persistence of CART cells.
Detailed description
Immunotherapy is a novel and promising approach for the treatment of solid tumors; immunotherapy with chimeric antigen receptor (CAR) T cells (CART cells) in particular has the potential advantage of targeted therapies that can invoke a rapid tumor response, and the advantage of long-lived responses that are the hallmark of engagement of the adaptive immune system such as memory T cells. This is a single arm, open-label, phase I study to determine the safety and feasibility of combination CART-meso cells (autologous T cells lentivirally transduced to express anti-mesothelin scFv fused to TCRζ and 4-1BB costimulatory domains) and CART19 cells (autologous T cells lentivirally transduced to express a humanized anti-CD19 scFv fused to TCRζ and 4-1BB costimulatory domains) in patients with pancreatic cancer following lymphodepletion with cyclophosphamide.
Interventions
BIOLOGICALCART-meso-19 T cells
A single dose of CART-meso-19 cells (combination therapy with CART-meso and CART19 cells) will be administered intravenously as two separate infusions. The dose is 1-3x107/m2 (Cohort 1) or 1-3x108/m2 (Cohort 2) CART positive cells. The infusion will be scheduled to occur 3 (±1) days after a single dose of 1.5 grams/m2 of cyclophosphamide, which will be administered according to standard procedures in the outpatient setting. Patients will receive CART cell treatment on an outpatient basis.
DRUGCyclophosphamide
A single dose of chemotherapy to be administered prior to dosing of the CART-meso-19 cells
Sponsors
University of California, San Francisco
University of Pennsylvania
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 years of age and older * 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 |
|---|---|
| Safety of IV administration of CART-meso-19 with cyclophosphamide as lymphodepleting chemotherapy in patients with pancreatic cancer using the NCI CTCAE v4.03 criteria | 24 months |
Countries
United States
Outcome results
None listed