Autologous CARTmeso/19 Against Pancreatic Cancer

Study Overview
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Brief Summary
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Pancreatic cancer patients receive chimeric antigen receptor (CAR) T cells against mesothelin (CARTmeso) or CD19 (CART19) cells administered at 3 days via pancreatic artery infusion or i.v. after preconditioning of cyclophosphamide. Both CART cells are autologous. CARTmeso cells target pancreatic cells which highly express mesothelin, while CART19 cells target tumor-associated B cells expressing cluster of differentiation antigen 19 (CD19) which are mostly immunosuppressive. The investigators hypothesize that this combination therapy may enhance the efficacy of CARTmeso cells in the body. Additionally, a medium dose of cyclophosphamide is used to enhance the engraftment of CART cells.

Detailed Description
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This is a single arm, open-label, pilot study to determine the safety and feasibility of combination CARTmeso cells and CART19 cells in patients with pancreatic cancer following lymphodepletion with cyclophosphamide. Both cells contain CAR proteins consisting of a murine-derived single chain antibody fragment (scFv), cluster of differentiation antigen 137 (41BB) co-stimulatory domain and cluster of differentiation antigen 3 zeta chain (CD3ζ) signaling domain transduced by lentivirus

Official Title
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Pilot Study of Autologous Chimeric Antigen Receptor Cells Against Mesothelin and CD19 in Patients With Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Biological: CARTmeso CART19


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent serum soluble mesothelin-related protein (SMRP) > 0.4 nanomolar/L Persistent cancer after at least one prior standard of care chemotherapy for advanced stage disease 18 years of age and ≤65 Life expectancy greater than 3 months Satisfactory organ and bone marrow function Exclusion Criteria: Participation in a therapeutic investigational study within 4 weeks prior to the screening visit Active invasive cancer other than pancreatic cancer HIV, hepatitis B/C virus, or infections Active autoimmune disease requiring immunosuppressive therapy within 4 weeks Planned concurrent treatment with systemic high dose corticosteroids Patients requiring supplemental oxygen therapy Pregnant or breastfeeding women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CARTmeso/19 treatment arm<br>Patients with pancreatic cancer receiving CARTmeso and CART19 autologous cells via artery infusion or i.v. with cyclophosphamide precondition | Biological: CARTmeso CART19<br>* Autologous chimeric antigen receptor T cells with murine scFv, 41BB co-stimulatory domain and CD3ζ signaling domain targeting mesothelin or CD19<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Adverse Events (AEs) ≥ grade 3 assessed through MedDra and CTCAE v4.03 [Time frame: from infusion to 3 month afterward] | Primary outcome is the percentage of adverse events (AEs) ≥ grade 3. AEs are assessed through MedDra and CTCAE v4.03. Any patients who receive any dose of CART cells will be evaluated | From first infusion to 3 months afterward | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate defined as any improvement measured by imaging following RECIST 1.1 [Time Frame: Day 14 and 1 month after infusion] | Secondary outcome is overall response rate. A response is defined as any improvement measured by imaging following RECIST 1.1. Only patients who receive infusions per protocol will be evaluated. | Day 14 and 1 month after infusion, or until patient withdraw consent or receive new therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CART, Pancreatic Cancer, artery infusion