Autologous CARTmeso/19 Against Pancreatic Cancer

Early Phase 1

• Conditions: Pancreatic Cancer
• Interventions: Biological: CARTmeso CART19

• Registration Number: NCT03497819
• Lead Sponsor: First Affiliated Hospital of Wenzhou Medical University

Brief Summary

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

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 Timeline

• Study Start: 2017-10-01
• Study First Submitted: 2017-10-27
• Status Verified: 2018-04
• Study First Submitted QC: 2018-04-12
• Last Update Submitted: 2018-04-12
• Study First Posted: 2018-04-13
• Last Update Posted: 2018-04-13
• Primary Completion: 2019-10-31
• Study Completion: 2020-10-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 10

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CARTmeso/19 treatment arm	CARTmeso CART19	Patients with pancreatic cancer receiving CARTmeso and CART19 autologous cells via artery infusion or i.v. with cyclophosphamide precondition

Primary Outcome Measures

Name	Time	Method
The Percentage of Adverse Events (AEs) ≥ grade 3 assessed through MedDra and CTCAE v4.03 [Time frame: from infusion to 3 month afterward]	From first infusion to 3 months 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

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate defined as any improvement measured by imaging following RECIST 1.1 [Time Frame: Day 14 and 1 month after infusion]	Day 14 and 1 month after infusion, or until patient withdraw consent or receive new therapy	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.

Trial Locations

Locations (1)

First Affiliated Hospital of Wenzhou Medical University; 🇨🇳 Wenzhou, Zhejiang, China