Clinical trial NCT02465983: Pilot Study of Autologous T-cells in Patients With Metastatic Pancreatic Cancer
Official title: Pilot Study of Autologous T-cells Redirected to Mesothelin and CD19 With a Chimeric Antigen Receptor in Patients With Metastatic Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Pancreatic Cancer
Keywords: Pancreatic Cancer
CAR / CART
T cells
Immunotherapy
Gene therapy
Redirected T cells
Autologous T cells
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: University of California, San Francisco
First posted: 2015-06-09
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 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
timeFrame: 24 months
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of Pennsylvania
name: Gabriela Plesa
role: STUDY_DIRECTOR
affiliation: University of California, San Francisco
name: Andrew Ko
role: PRINCIPAL_INVESTIGATOR
References: