Chimeric Switch Receptor Modified T Cells for Patients With PD-L1+ Recurrent or Metastatic Malignant Tumors

NCT ID: NCT02930967

Last Updated: 2016-10-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-31
• Study Completion Date: 2019-08-31

Brief Summary

A Chimeric Switch Receptor, which was constructed by fusing the PD1 extracellular ligand binding domain to the CD28 intracellular costimulatory domain, was designed to target PD-L 1 positive tumors . In this single-arm, open-label, one center, dose escalation clinical study, the main purpose is to determine the safety and efficacy of infusion of autologous Chimeric Switch Receptor modified T cells (CSR T) in adult patients with PD-L1 positive, recurrent or metastatic malignant tumors.

Conditions

Recurrent PD-L1+ Malignant Tumors; Metastatic PD-L1+ Malignant Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CSR T cells

A dose escalation clinical study aimed to assess the safety and efficacy of CSR T cells in patients with PD-L1 positive tumors.

CSR T dosage ranging from: 5×10^4 /kg to 1×10^7 /kg will be tested.

Group Type: EXPERIMENTAL

autologous CSR T

Intervention Type: BIOLOGICAL

Patients will be received a three-day regimen of chemotherapy consisting of cyclophosphamide aimed to deplete the lymphocytes. 1 to 4 days after lymphodepletion, a prescribed dose of CSR T cells will be intravenously infused to patient in a three-day split-dose regimen (day0,10%; day1, 30%; day2, 60%).

Interventions

autologous CSR T

Patients will be received a three-day regimen of chemotherapy consisting of cyclophosphamide aimed to deplete the lymphocytes. 1 to 4 days after lymphodepletion, a prescribed dose of CSR T cells will be intravenously infused to patient in a three-day split-dose regimen (day0,10%; day1, 30%; day2, 60%).

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Patients with PD-L1 positive, recurrent or metastatic malignant tumors , including but not limited to pancreatic cancer, renal cancer, colorectal cancer, lymphoma, breast cancer and lung cancer;

2. measurable tumors by RECIST1.1 standard;

3. patients are 18 to 70 years old;

4. life expectancy > 3months;

5. KPS ≥70;

6. 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 ;

7. Blood: Hgb ≥ 80 g/L, ANC ≥ 1×10^9/L, PLT ≥ 50×10^9/L;

8. 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 with 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, or have clinical signs of bone metastasis, such as bone and joint pain.

9. patients with brain metastasis, or have clinical signs of brain metastasis, such as loss of self-consciousness.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Marino Biotechnology Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

China Meitan General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jinwen Sun

Director of Department of General Surgery and Surgical Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jinwen Sun, MD

Role: PRINCIPAL_INVESTIGATOR

China Meitan General Hospital

Locations

China Meitan General Hospital

Beijing, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Shidong Wei, MD

Role: CONTACT

liqinghe9644679@163.com

+86-13146634751

Facility Contacts

Shidong Wei, MD

Role: primary

liqinghe9644679@163.com

+86-13146634751

Other Identifiers

K16-3

Identifier Type: -

Identifier Source: org_study_id