Autologous CARTmeso/19 Against Pancreatic Cancer

Sponsor

First Affiliated Hospital of Wenzhou Medical University (Other)

Overall Status

Unknown status

CT.gov ID

NCT03497819

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

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

Anticipated 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 :

Oct 1, 2017

Anticipated Primary Completion Date :

Oct 31, 2019

Anticipated Study Completion Date :

Oct 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

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

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

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:

Apr 13, 2018

Last Update Posted:

Apr 13, 2018

Last Verified:

Apr 1, 2018

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

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

CART

Pancreatic Cancer

artery infusion

Additional relevant MeSH terms:

Pancreatic Neoplasms

Study Results

No Results Posted as of Apr 13, 2018