A Study Of Mesothelin Redirected Autologous T Cells For Advanced Pancreatic Carcinoma

Study Overview

A Study of Mesothelin Redirected Autologous T Cells for Advanced Pancreatic Carcinoma

Pancreatic carcinoma typically has a high recurrence rate and very poor prognosis. Surgery is the best choice for the treatment of pancreatic cancer, but for those advanced pancreatic cancer patients，when surgery is not available，chemotherapy combined with radiation therapy or interventional therapy is commonly used in the treatment，but the prolonging survival effect is not obvious. And now, some clinical researchers use CAR-T cells in the treatment of pancreatic carcinoma, according to the existing results, therapeutic effects are not as good as expecting. One of the most likely reasons is that they continued to use the intravenous infusing of CART cells to patients, when the T cells into the blood circulation, will result in decreased tumor activity and more potential adverse effects. We believe that a suitable TAA targeted-CAR-T cells will be an effective way to treat cancer, as long as the pathway of the cell infused to the body can not only improve the drug concentration of the tumor site but reduce the potential off-target side effects. In order to achieve this goal, it is probably the best choice to use vascular intervention to mediate CAR-T cells infusion. Mesothelin is a cell-surface antigen implicated in tumor invasion, which is highly expressed in pancreatic carcinoma but low-level expressed in mesothelia. We design a 2nd CART cells targeted with mesothelin, and use vascular intervention mediated CAR-T infusion to patients. We hope deliver anti-mesothelin CART cells locally can reducing the side effects while enhancing the antitumor affect by more CART cells accumulate in tumor sites while less can reach normal mesothelial tissue.

This study is being conducted to assess vascular interventional therapy mediated anti-mesothelin-CAR-T(meso-CAR-T) cells safety and efficacy in treating patients with advanced pancreatic carcinoma.The investigators constructed a 2nd CAR, using mesothelin as target, using 4-1BB as co-stimulator. The source of T cells used to prepare CAR-T should be autologous. The infusion dose is (1-10)×106 meso-CAR positive T cells/kg, and the specific cells numbers depends on the situation of individual CAR-T cells preparation. The infusion way is vascular interventional mediated, which would undergo cannula--DSA radiography--CAR-T cells perfusion. The cells perfusion process would lasts 15min to 2 h, and the specific time depends on patent's tumor-burdened state.

Pancreatic Cancer

DRUG: TAI-meso-CART

Genechem meso-CART

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2016-03-08	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2016-03-08
First Submitted that Met QC Criteria 2016-03-08	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2016-03-11
First Posted (ESTIMATED) 2016-03-11	Results First Posted N/A	Last Verified 2016-03

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: TAI-meso-CART A single dose of meso-CART cells will be administered by vascular interventional mediated as one dose infusions. The dose is 1-10x106/kg meso-CAR positive T cells. The infusion will be scheduled to occur 2 days after a single dose of 1.5 grams/m2 of cyclo	DRUG: TAI-meso-CART TAI as a local drug delivery pathway, so that more T cells gathered at the tumor site, less T cells to migrate to the normal tissue, thereby enhancing the efficacy of anti-tumor, reducing the potential of side effects. And meso-CART is a 2nd CAR, with mes

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: TAI-meso-CART

A single dose of meso-CART cells will be administered by vascular interventional mediated as one dose infusions. The dose is 1-10x106/kg meso-CAR positive T cells. The infusion will be scheduled to occur 2 days after a single dose of 1.5 grams/m2 of cyclo

DRUG: TAI-meso-CART

TAI as a local drug delivery pathway, so that more T cells gathered at the tumor site, less T cells to migrate to the normal tissue, thereby enhancing the efficacy of anti-tumor, reducing the potential of side effects. And meso-CART is a 2nd CAR, with mes

Primary Outcome Measures	Measure Description	Time Frame
Number of patients with adverse event	asverse event is evaluated with CTCAE, version 4.0	6 weeks

Secondary Outcome Measures	Measure Description	Time Frame
Number of patients with tumor response	summarize tumor response by overal response rates	8 weeks
Detection of transferred T cells in the circulation using quantitative -PCR		8 weeks

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Xu Aimin, Dctor

Phone Number: 86-13918183196

Email: xuarmy@163.com

Study Contact Backup

Name: Yu Xuejun, Master

Phone Number: 86-18616108610

Email: yuxuejun@genechem.com.cn

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Mesothelin expression positive and histologically confirmed as pancreatic carcinoma;
Aged between 18 and 69;
Persistent cancer after at least one prior standard of care chemotherapy, has no willing for surgery or cannot be suitable for surgery patients with or without liver, lymph node metastasis;
Tumor is too big to surgical resection;
Life expectancy greater than 4 months;
Satisfactory organ and bone marrow function as defined by the following: (1) creatinine <1.5mg/dl; (2) albumin >2; (3) cardiac ejection fraction of >55%; (4) ALT/AST<3×the institution normal upper limit; (5) hemoglobin>9g/dl, bilirubin 2.0×the institution normal upper limit; (6) absolute neutrophil count >1,000/ul, platelets>75,000/ul;
Without bleeding disorder or coagulation disorders;
Don't allergy to radiocontrast agent;
Birth control;
Adequate venous access for apheresis, and no other contraindications for leukapheresis;
Voluntary informed consent is given.

Pregnant or lactating women;
Uncontrolled active infection;
Active hepatitis B or hepatitis C infection;
Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary;
Previously treatment with any gene therapy products;
Feasibility assessment during screening demonstrates<30% transduction of target lymphocytes, or insufficient expansion (<5-fold) in response to CD3/CD28 costimulation;
Any serious, uncontrolled diseases (including, but not limit to, unstable angina pectoris, congestive heart failure, grade III or IV cardiac disease, serious arrhythmia, liver and kidney disorders or metabolic diseases, CNS diseases).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Xu Aimin, Doctor, RenJi Hospital

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Resources

Patients

Caregivers

Clinical Trial Record