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A Study of Mesothelin Redirected Autologous T Cells for Advanced Pancreatic Carcinoma (meso-CART)

Primary Purpose

Pancreatic Cancer

Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
TAI-meso-CART
Sponsored by
Shanghai GeneChem Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Cancer

Eligibility Criteria

18 Years - 69 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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).

Sites / Locations

  • Renji Hospital, Shanghai Jiao Tong University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TAI-meso-CART

Arm Description

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 cyclophosphamide, which will be administered according to standard procedures. Patients will 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.

Outcomes

Primary Outcome Measures

Number of patients with adverse event
asverse event is evaluated with CTCAE, version 4.0

Secondary Outcome Measures

Number of patients with tumor response
summarize tumor response by overal response rates
Detection of transferred T cells in the circulation using quantitative -PCR

Full Information

First Posted
March 8, 2016
Last Updated
March 8, 2016
Sponsor
Shanghai GeneChem Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT02706782
Brief Title
A Study of Mesothelin Redirected Autologous T Cells for Advanced Pancreatic Carcinoma
Acronym
meso-CART
Official Title
An Open-label, Uncontrolled, Single-arm Pilot Study to Evaluate Vascular Interventional Therapy Mediated Mesothelin-targeted Chimeric Antigen Receptor T Cells in Advanced Pancreatic Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Unknown status
Study Start Date
March 2016 (undefined)
Primary Completion Date
February 2018 (Anticipated)
Study Completion Date
September 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai GeneChem Co., Ltd.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TAI-meso-CART
Arm Type
Experimental
Arm Description
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 cyclophosphamide, which will be administered according to standard procedures. Patients will 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.
Intervention Type
Drug
Intervention Name(s)
TAI-meso-CART
Other Intervention Name(s)
Transcatheter Arterial Infusion of meso-CART cells
Intervention Description
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 mesothelin as target protein, 4-1BB as co- stimulator
Primary Outcome Measure Information:
Title
Number of patients with adverse event
Description
asverse event is evaluated with CTCAE, version 4.0
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Number of patients with tumor response
Description
summarize tumor response by overal response rates
Time Frame
8 weeks
Title
Detection of transferred T cells in the circulation using quantitative -PCR
Time Frame
8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xu Aimin, Dctor
Phone
86-13918183196
Email
xuarmy@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yu Xuejun, Master
Phone
86-18616108610
Email
yuxuejun@genechem.com.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xu Aimin, Doctor
Organizational Affiliation
RenJi Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Renji Hospital, Shanghai Jiao Tong University School of Medicine
City
Shanghai
State/Province
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xu Aimin, Doctor
Phone
86-13918183196
Email
xuarmy@163.com
First Name & Middle Initial & Last Name & Degree
Yu Xuejun, Master
Phone
86-18616108610
Email
yuxuejun@genechem.com.cn

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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

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