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

A Safety and Efficacy Study of Chimeric Switch Receptor Modified T Cells in Patients With Recurrent or Metastatic Malignant Tumors

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.

Study Overview

• Status: Unknown
• Conditions: Recurrent PD-L1+ Malignant Tumors; Metastatic PD-L1+ Malignant Tumors
• Intervention / Treatment: Biological: autologous CSR T

• 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: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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: 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.	Biological: 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%).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety as assessed by incidents of treatment related adverse events as assessed by CTCAE V4.0.	safety of infusion of autologous CSR T cells with cyclophosphamide as lymphodepleting chemotherapy	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression-free survival		6 months
overall survival rate		2 years
treatment response rate of CSR T cell infusion	defined as the proportion of patients who achieved complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD).	4 weeks
proliferation of CSR T cells in patients		2 years
Persistence of CSR T cells in patients		2 years

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: Pathologic Processes; Disease Attributes; Neoplasms; Recurrence
• Other Study ID Numbers: K16-3

Plan for Individual participant data (IPD)

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