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Anti-MUC1 CAR T Cells and PD-1 Knockout Engineered T Cells for NSCLC

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ClinicalTrials.gov Identifier: NCT03525782
Recruitment Status : Recruiting
First Posted : May 16, 2018
Last Update Posted : May 16, 2018
Sponsor:
Collaborators:
Guangzhou Anjie Biomedical Technology Co., Ltd.
University of Technology, Sydney
Information provided by (Responsible Party):
Size Chen, The First Affiliated Hospital of Guangdong Pharmaceutical University

Tracking Information
First Submitted Date  ICMJE April 26, 2018
First Posted Date  ICMJE May 16, 2018
Last Update Posted Date May 16, 2018
Actual Study Start Date  ICMJE February 1, 2018
Estimated Primary Completion Date January 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 3, 2018)
Number of participants with adverse events and dose limiting toxicities as assessed by CTCAE v4.0 [ Time Frame: approximately 6 months ]
Safety and tolerability of dose of CART-cells and PD-1 Knockout T cells will be assessed using CTCAE v4.0.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: May 3, 2018)
  • Response Rate [ Time Frame: 6 months ]
    Will be assessed according to the revised RECIST guideline v1.1
  • Overall Survival - OS [ Time Frame: Up to 24 months ]
    Measure the time from enrollment to death
  • Progression free survival - PFS [ Time Frame: Up to 12 months ]
    Time from enrollment to date of first documented progression or date of death.
  • Median CAR-T cell persistence [ Time Frame: 4 years ]
    Will be measured by quantitative RT-PCR
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Anti-MUC1 CAR T Cells and PD-1 Knockout Engineered T Cells for NSCLC
Official Title  ICMJE A Clinical Study of Anti-MUC1 CAR T Cells and PD-1 Knockout Engineered T Cells for Patients With Advanced Non-small Cell Lung Cancer
Brief Summary The study is to assess the safety and efficacy of the anti-MUC1 CAR T cells and /or PD-1 knockout engineered T cells for patients with advanced non-small cell lung cancer.
Detailed Description This is a combined phase 1 and 2 clinical study. The study is to assess the safety and efficacy of the anti-MUC1 CAR T cells and /or PD-1 knockout engineered T cells for patients with advanced non-small cell lung cancer. The treatment outcomes will be compared.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE
  • Lung Neoplasm Malignant
  • Non-small Cell Lung Cancer
Intervention  ICMJE
  • Biological: CAR-T Cells
    Using the T cells from the patients to produce anti-MUC1 CAR-T Cells and then the cells will be infused back to the patients.
  • Combination Product: CAR-T combining PD-1 Knockout
    Using the T cells from the patients to prepare anti-MUC1 CAR-T Cells and PD-1 knockout T cells, then the cells will be infused back to the patients
  • Biological: PD-1 knockout
    Using the T cells from the patients to prepare PD-1 knockout T cells, then the cells will be infused back to the patients
  • Drug: PD-1 mAb
    Patients will be treated with an identical course with a FDA approved monoclonal antibody against PD-1
    Other Name: Keytruda
  • Other: Sham control
    Patient's T cell will treated ex vivo with modification and then infused back in a similar time course.
Study Arms  ICMJE
  • Experimental: CAR-T
    Anti-MUC1 CAR-T cells will be prepared ex vivo and infused back to the patients.
    Intervention: Biological: CAR-T Cells
  • Experimental: CAR-T combining PD-1 knockout
    Anti-MUC1 CAR-T cells and PD-1 knockout Engineered T cells will be prepared ex vivo and infused back to the patients.
    Interventions:
    • Biological: CAR-T Cells
    • Combination Product: CAR-T combining PD-1 Knockout
    • Biological: PD-1 knockout
  • Experimental: PD-1 knockout
    PD-1 knockout Engineered T cells will be prepared ex vivo and infused back to the patients.
    Intervention: Biological: PD-1 knockout
  • Active Comparator: PD-1 mAb
    Patients will be treated with a FDA approved monoclonal antibody for an identical course of treatment. This group will serve as PD-1 antibody treated group.
    Intervention: Drug: PD-1 mAb
  • Placebo Comparator: Sham Control
    Patient's T cells will be separate without genetic or engineered modification ex vivo and infused back to the patients.
    Intervention: Other: Sham control
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 3, 2018)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 31, 2022
Estimated Primary Completion Date January 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • MUC1 is expressed in malignancy tissues by immuno-histochemical (IHC).
  • Eastern cooperative oncology group (ECOG) performance status of 0-1 or karnofsky performance status (KPS) score is higher than 60.
  • Patients have a life expectancy > 12 weeks.
  • Adequate venous access for apheresis or venous sampling, and no other contraindications for leukapheresis.
  • Negative pregnancy test for females of child-bearing potentials.
  • Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements: White blood cell count (WBC) ≥ 2500c/ml, Platelets ≥ 50×10^9/L, Hb ≥ 9.0g/dL, lymphocyte (LY) ≥ 0.7×10^9/L, LY% ≥ 15%, Alb ≥ 2.8g/dL, serum lipase and amylase < 1.5×upper limit of normal, serum creatinine ≤ 2.5mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5×upper limit of normal, serum total bilirubin ≤ 2.0mg/dL. These tests must be conducted within 7 days prior to registration.
  • Signed informed consent form.

Exclusion Criteria:

  • Number of T cells is less than 10% or the amplification of the T cells via artificial antigen presenting cell (aAPC) stimulation is less than 5 times.
  • Patients with symptomatic central nervous system (CNS) involvement.
  • Pregnant or nursing women.
  • Known HIV infection.
  • Serious illness or medical condition which would not permit the patient to be managed according to the protocol, including active uncontrolled infection, major cardiovascular, coagulation disorders, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive/restrictive pulmonary disease, or psychiatric or emotional disorders.
  • History of severe immediate hypersensitivity to any of the agents including cyclophosphamide, fludarabine, or aldesleukin.
  • Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
  • Previously treatment with any gene therapy products.
  • The existence of unstable or active ulcers or gastrointestinal bleeding. Patients with portal vein vascular invasion or extrahepatic, are excluded from this study.
  • Patients with a history of organ transplantation or are waiting for organ transplantation.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03525782
Other Study ID Numbers  ICMJE 2018-006
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Size Chen, The First Affiliated Hospital of Guangdong Pharmaceutical University
Study Sponsor  ICMJE The First Affiliated Hospital of Guangdong Pharmaceutical University
Collaborators  ICMJE
  • Guangzhou Anjie Biomedical Technology Co., Ltd.
  • University of Technology, Sydney
Investigators  ICMJE Not Provided
PRS Account The First Affiliated Hospital of Guangdong Pharmaceutical University
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP