Pilot Study of Autologous T-cells Redirected to Mesothelin and CD19 With a Chimeric Antigen Receptor in Patients With Metastatic Pancreatic Cancer
Overview
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- University of Pennsylvania
- Enrollment
- 4
- Locations
- 1
- Primary Endpoint
- 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
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts 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
Arms & Interventions
CART-meso-19 T cells
A single dose of CART-meso-19 T 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.
Intervention: CART-meso-19 T cells (Biological)
CART-meso-19 T cells
A single dose of CART-meso-19 T 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.
Intervention: Cyclophosphamide (Drug)
Outcomes
Primary Outcomes
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
Time Frame: 24 months
Secondary Outcomes
No secondary outcomes reported