Anti-mesothelin CAR T Cells for Patients With Recurrent or Metastatic Malignant Tumors

A Safety and Efficacy Study of Autologous T Cells Engineered to Express Chimeric Antigen Receptor Targeting Mesothelin in Patients With Recurred or Metastatic Malignant Tumors

This is a single-arm, open-label, one center, dose escalation clinical study, to determine the safety and efficacy of infusion of autologous T cells engineered to express chimeric antigen receptor targeting mesothelin in adult patients with mesothelin positive, recurrent or metastatic malignant tumors.

Study Overview

• Status: Unknown
• Conditions: Mesothelin Positive Tumors
• Intervention / Treatment: Biological: anti-mesothelin CAR T cells

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Shidong Wei, MD; Phone Number: +86-13146634751; Email: liqinghe9644679@163.com

Study Locations

• China
  • Beijing, China, 100028
    • Recruiting
    • China Meitan General Hospital
    • Contact: Shidong Wei, MD; Phone Number: +86-13146634751; Email: liqinghe9644679@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. patients with mesothelin positive, recurrent or metastatic malignant tumors , including but not limited to pancreatic adenocarcinoma, ovarian cancer, or pleural mesothelioma.
2. relapsed or metastatic after standard treatment
3. measurable tumors by RECIST1.1 standard
4. patients are 18 to 70 years old.
5. life expectancy > 3months.
6. KPS ≥70.
7. satisfactory major organ functions: adequate heart function with LVEF≥50%; no obvious abnormities in ECG; pulse oximetry ≥ 90%; cockcroft-gault creatinine clearance≥40 ml/min; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3ULN; Bilirubin ≤2.0 mg/dl .
8. Blood: Hgb ≥ 80 g/L, ANC ≥ 1×10^9/L, PLT ≥ 50×10^9/L.
9. women of reproductive potential must have a negative pregnancy test. Male and female of reproductive potential must agree to use birth control during the study and one year post study.

Exclusion Criteria:

1. patients with a prior history of autoimmune disease or other diseases who need long-term use of systemic hormone drug or immunosuppressive therapy
2. active infection.
3. HIV positive.
4. active hepatitis B virus infection or hepatitis C virus infection.
5. currently enrolled in other study.
6. patients, in the opinion of investigators, may not be eligible or are not able to comply with the study.
7. patients who have allergic disease, or are allergic to T cell products or other biological agents used in the study.
8. patients whose tumors have metastasized to bone marrow, or have clinical signs of bone metastasis, such as bone and joint pain .
9. patients who have brain metastasis or signs of brain metastasis, such as loss of self-consciousness.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: anti-mesothelin CAR T cells; Dose escalation study aimed to assess the safety and efficacy of anti-mesothelin CAR T cells. CAR T dosage ranging from 5×10^4 /kg to 1×10^7 /kg will be tested .	Biological: anti-mesothelin CAR T cells; Patients will be received a three-day regimen of chemotherapy consisting of cyclophosphamide aimed to deplete the lymphocytes. 1 to 4 days after lymphodepletion, patients are intravenously infused with anti-mesothelin CAR T cells in a three-day split-dose regimen (day0,10%; day1, 30%; day2, 60%).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
safety of infusion of autologous anti-mesothelin CAR T cells as assessed by the incidents of treatment related adverse events per NCI CTCAE V4.0	incidents of treatment related adverse events per NCI CTCAE V4.0	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival		2 years
progression free survival		6 months
treatment response rate of anti-mesothelin CAR T cells	Defined as the overall response rate (ORR), the proportion of patients who achieved complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD) based on the response evaluation criteria in solid tumor version 1.1 (RECIST1.1).	4 weeks
proliferation of anti-mesothelin CAR T cells in patients	measured by quantitative PCR and flow cytometry	6 months
activation of anti-mesothelin CAR T cells in patients	measured by blood cytokine levels after CAR T cell infusion	6 months
persistence of anti-mesothelin CAR T cells in patients	measured by quantitative PCR and flow cytometry	1 year

Collaborators and Investigators

• Sponsor: China Meitan General Hospital
• Collaborators: Marino Biotechnology Co., Ltd.
• Investigators: Principal Investigator: Jinwen Sun, MD, China Meitan General Hospital

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (Anticipated): August 1, 2018
• Study Completion (Anticipated): August 1, 2019

Study Registration Dates

• First Submitted: October 10, 2016
• First Submitted That Met QC Criteria: October 11, 2016
• First Posted (Estimate): October 12, 2016

Study Record Updates

• Last Update Posted (Estimate): October 12, 2016
• Last Update Submitted That Met QC Criteria: October 11, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: K16-4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided