Autologous CARTmeso/19 Against Pancreatic Cancer

Early Phase 1UnknownNCT03497819

First Affiliated Hospital of Wenzhou Medical University10 enrolled

Overview

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.

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

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Pancreatic Cancer

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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

Time frame: From first infusion to 3 months afterward

Secondary Outcomes

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.

Time frame: Day 14 and 1 month after infusion, or until patient withdraw consent or receive new therapy