Autologous CARTmeso/19 Against Pancreatic Cancer

• ClinicalTrials.gov Identifier: NCT03497819
• Recruitment Status: Unknown
• First Posted: April 13, 2018
• Last Update Posted: April 13, 2018
• Sponsor: First Affiliated Hospital of Wenzhou Medical University
• Information provided by (Responsible Party): Meng-Tao Zhou, First Affiliated Hospital of Wenzhou Medical University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Pancreatic Cancer	Biological: CARTmeso CART19	Early Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pilot Study of Autologous Chimeric Antigen Receptor Cells Against Mesothelin and CD19 in Patients With Pancreatic Cancer
• Actual Study Start Date: October 1, 2017
• Estimated Primary Completion Date: October 31, 2019
• Estimated Study Completion Date: October 31, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

1. Overall Response Rate defined as any improvement measured by imaging following RECIST 1.1 [Time Frame: Day 14 and 1 month after infusion] [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

China, Zhejiang

First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China, 325000

Sponsors and Collaborators

First Affiliated Hospital of Wenzhou Medical University

Investigators

• Principal Investigator: Mengtao Zhou, MD; First Affiliated Hospital of Wenzhou Medical University

More Information

• Responsible Party: Meng-Tao Zhou, Director, First Affiliated Hospital of Wenzhou Medical University
• ClinicalTrials.gov Identifier: NCT03497819
• Other Study ID Numbers: YXA-meso19
• First Posted: April 13, 2018
• Last Update Posted: April 13, 2018
• Last Verified: April 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Meng-Tao Zhou, First Affiliated Hospital of Wenzhou Medical University:

CART; Pancreatic Cancer; artery infusion

Additional relevant MeSH terms:

Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases