Trial | NCT03060343  Report issue

Title

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

  • Phase

    Early Phase 1

  • Study Type

    Interventional

  • Status

    Unknown status

  • Study Participants

    10
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.
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).
Study Started
Nov 28
2016
Primary Completion
Nov 28
2018
Anticipated
Study Completion
Nov 28
2019
Anticipated
Last Update
Feb 23
2017

Biological Zeushield Cytotoxic T Lymphocytes

Three dose levels will be evaluated. Dose Level One: 1.0×10^5 cells/kg, Dose Level Two: 1.0×10^6 cells/kg, Dose Level Three: 1.0×10^7 cells/kg. At the discretion of the investigator, if patients with active disease have stable disease or a response at week 8 or on subsequent evaluations, they are eligible to receive up to 6 additional infusions at 8 to 12 week intervals.

Zeushield Cytotoxic T Lymphocytes Experimental

Enrolled patients will receive Zeushield Cytotoxic T Lymphocytes by infusion

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
No Results Posted