Clinical Trials /

Zeushield Cytotoxic T Lymphocytes (Z-CTLs) for Relapsed or Refractory Non Small Cell Lung Cancer (NSCLC)

NCT03060343

Description:

A single-center, open-label pilot study to determine the safety, tolerance and engraftment potential of zeushield cytotoxic T lymphocytes in subjects with PD-L1+ positive non-small cell lung cancer.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Zeushield Cytotoxic T Lymphocytes (Z-CTLs) for Relapsed or Refractory Non Small Cell Lung Cancer (NSCLC)
  • Official Title: Preliminary Clinical Study of Autologous T Cells Modified Chimeric Antigen Receptor (CAR) Targeting PD-L1 and CD80/CD86 (Zeushield Cytotoxic T Lymphocytes) for the Treatment of Recurrent or Refractory Non Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: Z-NSCLC-01
  • NCT ID: NCT03060343

Conditions

  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
Zeushield Cytotoxic T LymphocytesZeushield Cytotoxic T Lymphocytes

Purpose

A single-center, open-label pilot study to determine the safety, tolerance and engraftment potential of zeushield cytotoxic T lymphocytes in subjects with PD-L1+ positive non-small cell lung cancer.

Detailed Description

      The purpose of this first in human study is to determine the safety and feasibility of
      Zeushield Cytotoxic T Lymphocytes(Z-CTLs) in patients with relapsed or refractory NSCLC.
      Z-CTLs therapy is a novel immunotherapy under investigation in which patients have their
      T-cells (a type of white blood cell) collected and modified in the laboratory, before they
      are given back to the patient. The T-cells are modified to transform the intracellular signal
      domain of PD-1 and CTLA-4 to immune activation stimulus signal and transform T cells to a new
      kind of cancer-killer cells: zeushield cytotoxic T lymphocytes (Z-CTls).
    

Trial Arms

NameTypeDescriptionInterventions
Zeushield Cytotoxic T LymphocytesExperimentalEnrolled patients will receive Zeushield Cytotoxic T Lymphocytes by infusion

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Men or women aged >18 years old
    
              -  Subjects are diagnosed as refractory, recurrent ,metastatic, advanced non-small cell
                 lung cancer by histological and cytological methods including specific lesion-targeted
                 brush biopsy, lavage and fine needle aspiration;
    
              -  Have at least one new measurable tumor lesion compared with previous irradiated region
    
              -  Tumor tissues samples confirmed as PD-L1 positive
    
              -  Expected survival≥12 weeks
    
              -  ECOG scored as 0-1 or KPS grading > 80
    
              -  PLT≥100000/mm3
    
              -  Hb≥9.0g/dL
    
              -  Serum creatinine≤2.5mg/dL,CCR≥50ml/min (renal malfunction defined as CCR<50ml/min
                 according to Cockroft-Gault formula)
    
              -  ALT and AST≤2.5ULN; for liver metastasis,ALT and AST ≤5ULN
    
              -  Serum TBiL≤3.0mg/dL, TBiL≤2.5ULN
    
              -  PT: INR < 1.7 or extended PT to normal value < 4s
    
              -  Adequate venous access for apheresis or venous blood collection, and no other
                 contraindication of blood cell separation
    
              -  Patients with willingness to be in this study and able to provide informed consent
    
              -  Capable of receiving treatment and follow up, included subjects are required to
                 receive treatment in the enrolled centre
    
              -  Women of childbearing age are required to take acceptable measures to minimize the
                 possibility of pregnancy during whole session. Women of childbearing age must have
                 negative results of serum or urine tests within 24 hours prior to infusion. Women
                 subjects must not be in lactation;
    
            Exclusion Criteria:
    
              -  pregnant women or women in lactation
    
              -  active HBV or HCV infection
    
              -  HIV/AIDS infection
    
              -  active infection
    
              -  previously suffered from diseases or concurrent diseases as followed:
    
              -  patients confirmed as severe autoimmune diseases in long-term (over 2 months) need of
                 systemic immune inhibitors (steroid) or as immune-mediated symptomatic diseases
                 including ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus
                 erythematosus (SLE), autoimmune vasculitis (for example, Wegener's granulomatosis)
    
              -  subjects with previous diagnosis as motor neurone disease caused by autoimmunity
    
              -  subjects previously suffered from toxic epidermal necrolysis (TEN)
    
              -  subjects with any mental diseases including dementia, mental status change that may
                 impinge the understanding and performance of informed consent and related
                 questionnaire
    
              -  subjects with severe, uncontrollable diseases judged by investigators that may hinder
                 them receiving this treatment
    
              -  subjects with previously active malignant tumors including basal or squamous skin
                 cancer, superficial bladder cancer, and in situ breast carcinoma within 5 years who
                 had been completely cured without the need of follow-up treatment are not excluded.
    
              -  during ongoing treatment using systemic steroid or steroid inhalants
    
              -  subjects with unstable or active peptic ulcer or alimentary tract hemorrhage
    
              -  subjects with previous organ transplantation or ready for organ transplantation
    
              -  subjects in need of anticoagulant therapy treatment (warfarin or heparin)
    
              -  subjects judged by investigators as not appropriate for this study
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
    Time Frame:8 weeks
    Safety Issue:
    Description:Observe and determine the potential adverse events related to the escalating dose infusion of Z-CTLs such as high fever,jaundice, kidney failure and so on.

    Secondary Outcome Measures

    Measure:Number of Z-CTLs in peripheral blood samples after infusion
    Time Frame:8 weeks
    Safety Issue:
    Description:Detect Z-CTLs in peripheral blood samples after infusion by flow cytometry every week
    Measure:Objective response rate (ORR)
    Time Frame:2 years
    Safety Issue:
    Description:the ratio of patients diagnosed as partial remission (PR) to complete remission (CR) according to RECIST 1.1 criteria
    Measure:Progression free survival (PFS)
    Time Frame:2 years
    Safety Issue:
    Description:the duration from baseline to PD (audited and confirmed by independent imaging), or to the day of any death event
    Measure:Time to tumor progression (TTP)
    Time Frame:2 years
    Safety Issue:
    Description:the duration from baseline to disease starts to get worse or spreads to other parts of the body
    Measure:Overall survival (OS)
    Time Frame:2 years
    Safety Issue:
    Description:the time period from the 1st day of treatment to the day of death for any reason. For patients who are still alive at the data analysis day, OS data is subject to the last confirmed time of survival patients

    Details

    Phase:Early Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Yu Fenglei

    Last Updated

    February 18, 2017