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PD-1 Knockout Engineered T Cells for Castration Resistant Prostate Cancer

This study is not yet open for participant recruitment.
Verified August 2016 by Yinglu Guo, Peking University
Sponsor:
ClinicalTrials.gov Identifier:
NCT02867345
First Posted: August 15, 2016
Last Update Posted: August 16, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Cell Biotech Co., Ltd.
Information provided by (Responsible Party):
Yinglu Guo, Peking University
  Purpose
This study will evaluate the safety of PD-1 knockout engineered T cells in treating castration resistant prostate cancer (CRPC). Blood samples will also be collected for research purposes.

Condition Intervention Phase
Hormone Refractory Prostate Cancer Biological: PD-1 Knockout T Cells Drug: Cyclophosphamide Drug: IL-2 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Dose-escalation Phase I Trial of PD-1 Knockout Engineered T Cells for the Treatment of Castration Resistant Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Yinglu Guo, Peking University:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]
  • 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 ]

Estimated Enrollment: 20
Study Start Date: November 2016
Estimated Study Completion Date: December 2020
Estimated Primary Completion Date: November 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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)
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 wild-type 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).
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)

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.
  Eligibility

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Ages Eligible for Study:   45 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pathologically and clinical verified castration resistant prostate 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
  • 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02867345


Contacts
Contact: Wujiang Liu, MD and PhD 861083575825 liuwujiang@bjmu.edu.cn
Contact: Liqun Zhou, MD and PhD 861083575811 zhoulqmail@sina.com

Locations
China, Beijing
Department of Urology Peking University First Hospital
Beijing, Beijing, China, 100034
Sponsors and Collaborators
Peking University
Cell Biotech Co., Ltd.
Investigators
Principal Investigator: Yinglu Guo, MD Peking University First Hospital
  More Information

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Yinglu Guo, Professor, Peking University
ClinicalTrials.gov Identifier: NCT02867345     History of Changes
Other Study ID Numbers: 11007965939
First Submitted: August 11, 2016
First Posted: August 15, 2016
Last Update Posted: August 16, 2016
Last Verified: August 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Plan to open

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Cyclophosphamide
Interleukin-2
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents