Clinical Trials /

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

NCT02930967

Description:

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.

Related Conditions:
  • Lymphoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Chimeric Switch Receptor Modified T Cells for Patients With PD-L1+ Recurrent or Metastatic Malignant Tumors
  • Official Title: A Safety and Efficacy Study of Chimeric Switch Receptor Modified T Cells in Patients With Recurrent or Metastatic Malignant Tumors

Clinical Trial IDs

  • ORG STUDY ID: K16-3
  • NCT ID: NCT02930967

Conditions

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

Interventions

DrugSynonymsArms
autologous CSR TCSR T cells

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
CSR T cellsExperimentalA 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.
  • autologous CSR T

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.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:China Meitan General Hospital

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