pilot study of autologous t-cells in patients with metastatic pancreatic cancer

Conditions: Pancreatic Cancer

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.

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.

Eligibility criteria:
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

Keywords: pancreatic cancer car / cart t cells immunotherapy gene therapy redirected t cells autologous t cells