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PD-1 Knockout Engineered T Cells for Metastatic Non-small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT02793856
Recruitment Status : Active, not recruiting
First Posted : June 8, 2016
Last Update Posted : January 23, 2019
Sponsor:
Collaborator:
Chengdu MedGenCell, Co., Ltd.
Information provided by (Responsible Party):
You Lu, Sichuan University

Tracking Information
First Submitted Date  ICMJE May 30, 2016
First Posted Date  ICMJE June 8, 2016
Last Update Posted Date January 23, 2019
Actual Study Start Date  ICMJE August 2016
Estimated Primary Completion Date June 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 7, 2016)
Number of participants with Adverse Events and/or Dose Limiting Toxicities as a Measure of Safety and tolerability of dose of PD-1 Knockout T cells using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in patients [ Time Frame: Dose Escalation - Approximately 6 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02793856 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 17, 2018)
  • Response Rate [ Time Frame: 3 months ]
    Response will be evaluated according to RECIST v1.1
  • 8 weeks-Disease Control Rate (DCR) [ Time Frame: 8 weeks ]
    Response will be evaluated according to RECIST v1.1
  • Progression free survival - PFS [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to average 10 months ]
  • Overall Survival - OS [ Time Frame: The time from randomization to death from any cause, assessed up to 2 years ]
  • Peripheral blood circulating tumor DNA [ Time Frame: 6 weeks ]
    Peripheral circuiting tumor DNA is collected at baseline and 6 weeks after last treatment
  • Temporal Interleukin-10 change in the peripheral blood [ Time Frame: Baseline and 1 month and 3 months ]
  • Temporal tumour necrosis factor-α change in the peripheral blood [ Time Frame: Baseline and 1 month and 3 months ]
  • Temporal Interleukin-6 change in the peripheral blood [ Time Frame: Baseline and 1 month and 3 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 7, 2016)
  • Response Rate [ Time Frame: 90 days ]
    Response will be evaluated according to RECIST v1.1
  • Cytokine changes in the peripheral blood [ Time Frame: Baseline and 1 month and 3 months ]
    interleukin-2, Interferon-γ, Tumour necrosis factor-a, and, interleukin-6 will be analyzed.
  • Progression free survival - PFS [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to average 10 months ]
  • Overall Survival - OS [ Time Frame: The time from randomization to death from any cause, assessed up to 2 years ]
  • Peripheral blood circuiting tumor DNA [ Time Frame: 6 weeks ]
    Peripheral circuiting tumor DNA is collected at baseline and 6 weeks after last treatment
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE PD-1 Knockout Engineered T Cells for Metastatic Non-small Cell Lung Cancer
Official Title  ICMJE A Phase I Clinical Trial of PD-1 Knockout Engineered T Cells Treating Patients With Advanced Non-small Cell Lung Cancer
Brief Summary This study will evaluate the safety of PD-1 knockout engineered T cells in treating metastatic non-small cell lung cancer. Blood samples will also be collected for research purposes.
Detailed Description This is a dose-escalation study of ex-vivo knocked-out, expanded, and selected PD-1 knockout-T cells from autologous origin. Patients are assigned to 1 of 3 treatment groups to determine the maximal tolerant dose. After the lower number of cycles are considered tolerant, an arm of the next higher number of cycles will be open to next patients. Biomarkers and immunological markers are collected and analyzed as well.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Non-small Cell Lung Cancer
Intervention  ICMJE
  • Drug: Cyclophosphamide
    To deplete Tregs before collecting peripheral blood
    Other Name: Cytoxan
  • Other: PD-1 Knockout T Cells
    Autologous lymphocytes are collected and PDCD1 gene is knocked out in the laboratory. Cells are selected and expanded ex vivo. Cells are infused back to the patients for treatment
Study Arms  ICMJE
  • Experimental: A - Two cycles

    Peripheral blood lymphocytes will be collected and Programmed cell death protein 1(PDCD1) gene will be knocked out by CRISPR Cas9 in the laboratory (PD-1 Knockout T cells). The lymphocytes will be selected and expanded ex vivo and infused back into patients. Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion.

    A total of 1 x 10^7/kg PD-1 Knockout T cells will be infused in one cycle. Each cycle is divided into three administrations, with 20% infused in the first administration, 30% in the second, and the remaining 50% in the third. Patients will receive a total of two cycles of treatment.

    Interventions:
    • Drug: Cyclophosphamide
    • Other: PD-1 Knockout T Cells
  • Experimental: B- Two cycles

    Peripheral blood lymphocytes will be collected and Programmed cell death protein 1(PDCD1) gene will be knocked out by CRISPR Cas9 in the laboratory (PD-1 Knockout T cells). The lymphocytes will be selected and expanded ex vivo and infused back into patients. Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion.

    A total of 2 x 10^7/kg PD-1 Knockout T cells will be infused in one cycle. Each cycle is divided into three administrations, with 20% infused in the first administration, 30% in the second, and the remaining 50% in the third. Patients will receive a total of two cycles of treatment.

    Interventions:
    • Drug: Cyclophosphamide
    • Other: PD-1 Knockout T Cells
  • Experimental: C- Two cycles

    Peripheral blood lymphocytes will be collected and Programmed cell death protein 1(PDCD1) gene will be knocked out by CRISPR Cas9 in the laboratory (PD-1 Knockout T cells). The lymphocytes will be selected and expanded ex vivo and infused back into patients. Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion.

    A total of 4 x 10^7/kg PD-1 Knockout T cells will be infused in one cycle. Each cycle is divided into three administrations, with 20% infused in the first administration, 30% in the second, and the remaining 50% in the third. Patients will receive a total of two cycles of treatment.

    Interventions:
    • Drug: Cyclophosphamide
    • Other: PD-1 Knockout T Cells
Publications *

*   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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 17, 2018)
12
Original Estimated Enrollment  ICMJE
 (submitted: June 7, 2016)
15
Estimated Study Completion Date  ICMJE June 30, 2019
Estimated Primary Completion Date June 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Pathologically verified stage IV non-small cell lung cancer with measurable lesions (On CT: longest diameter of tumoral lesion >=10 mm, shorted diameter of lymph node >=15 mm; measurable lesions should not have been irradiated)
  • Progressed after all standard treatment
  • Performance score: 0-1
  • Expected life span: >= 6 months
  • Toxicities from prior treatment has resolved. Washout period is 4 weeks for chemotherapy, and 2 weeks for targeted therapy
  • Major organs function normally
  • Women at pregnant ages should be under contraception
  • Willing and able to provide informed consent

Exclusion Criteria:

  • Pathology is mixed type
  • Emergent treatment of tumor emergency is needed
  • Poor vasculature
  • Coagulopathy, or ongoing thrombolytics and/or anticoagulation
  • Blood-borne infectious disease, e.g. hepatitis B
  • History of mandatory custody because of psychosis or other psychological disease inappropriate for treatment deemed by treating physician
  • With other immune diseases, or chronic use of immunosuppressants or steroids
  • Compliance cannot be expected
  • Other conditions requiring exclusion deemed by physician
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 Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02793856
Other Study ID Numbers  ICMJE MHC-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party You Lu, Sichuan University
Study Sponsor  ICMJE Sichuan University
Collaborators  ICMJE Chengdu MedGenCell, Co., Ltd.
Investigators  ICMJE
Principal Investigator: You Lu, MD Sichuan University
PRS Account Sichuan University
Verification Date January 2019

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