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PD-1 Knockout Engineered T Cells for Muscle-invasive Bladder Cancer

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ClinicalTrials.gov Identifier: NCT02863913
Recruitment Status : Withdrawn (No funding)
First Posted : August 11, 2016
Last Update Posted : March 6, 2019
Sponsor:
Information provided by (Responsible Party):
Wujiang Liu, Peking University

Tracking Information
First Submitted Date  ICMJE August 1, 2016
First Posted Date  ICMJE August 11, 2016
Last Update Posted Date March 6, 2019
Study Start Date  ICMJE September 2016
Estimated Primary Completion Date September 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 8, 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 NCT02863913 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 8, 2016)
  • Response Rate:Response will be evaluated according to RECIST v1.1 [ Time Frame: 90 days ]
  • 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-2 change in the peripheral blood [ Time Frame: Baseline and 1 month and 3 months ]
  • Temporal Interferon-γ 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 Same as current
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE PD-1 Knockout Engineered T Cells for Muscle-invasive Bladder Cancer
Official Title  ICMJE A Dose-escalation Phase I Trial of PD-1 Knockout Engineered T Cells for the Treatment of Muscle-invasive Bladder Cancer
Brief Summary This study will evaluate the safety of PD-1 knockout engineered T cells in treating metastatic advanced bladder 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 Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Invasive Bladder Cancer Stage IV
Intervention  ICMJE
  • Biological: PD-1 Knockout T Cells
    PD-1 Knockout T Cells and PD-1 wild-type T Cells will be made by Cell Biotech Co., Ltd. 2x107/kg T cells will be used for test group and comparable group separately.
  • Drug: Cyclophosphamide

    Cyclophosphamide at 20mg/kg single dose will be administered 3 days i.v. before cell infusion.

    Interleukin-2 (IL-2) will be given in the following 5 days, 720000 international unit(IU)/Kg/day (if tolerant).

    Other Name: cytophosphane
  • Drug: IL-2
    Interleukin-2 (IL-2) will be given in the following 5 days after cell infusion, 720000 international unit(IU)/Kg/day (if tolerant).
    Other Name: Interleukin-2 (IL-2)
Study Arms
  • Experimental: Test group
    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.Interleukin-2 (IL-2) will be given in the following 5 days, 720000 international unit(IU)/Kg/day (if tolerant). Patients will receive a total of 2, 3, 4 cycles of treatment.
    Interventions:
    • Biological: PD-1 Knockout T Cells
    • Drug: Cyclophosphamide
    • Drug: IL-2
  • Placebo Comparator: Comparable group

    Peripheral blood lymphocytes will be collected and Programmed cell death protein 1(PDCD1) gene will not be knocked out by CRISPR Cas9 in the laboratory (PD-1 Wild-type 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.

    Interleukin-2 (IL-2) will be given in the following 5 days, 720000 international unit(IU)/Kg/day (if tolerant).

    Interventions:
    • Drug: Cyclophosphamide
    • Drug: IL-2
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 Withdrawn
Actual Enrollment  ICMJE
 (submitted: March 4, 2019)
0
Original Estimated Enrollment  ICMJE
 (submitted: August 8, 2016)
20
Estimated Study Completion Date September 2019
Estimated Primary Completion Date September 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Pathologically verified stage IV muscle-invasive bladder 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
Sexes Eligible for Study: All
Ages 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers 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 NCT02863913
Other Study ID Numbers  ICMJE 11007965938
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: Undecided
Plan Description: plan to share
Responsible Party Wujiang Liu, Peking University
Study Sponsor  ICMJE Peking University
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Peking University
Verification Date August 2016

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