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PD-1 Knockout Engineered T Cells for Metastatic Renal Cell Carcinoma.

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified August 2016 by Peking University
Sponsor:
Collaborator:
Cell Biotech Co., Ltd.
Information provided by (Responsible Party):
Yinglu Guo, Peking University
ClinicalTrials.gov Identifier:
NCT02867332
First received: August 11, 2016
Last updated: NA
Last verified: August 2016
History: No changes posted
  Purpose
This study will evaluate the safety of PD-1 knockout engineered T cells in treating metastatic advanced renal cancer. Blood samples will also be collected for research purposes.

Condition Intervention Phase
Metastatic Renal Cell Carcinoma
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: Open Label
Primary Purpose: Treatment
Official Title: A Dose-escalation Phase I Trial of PD-1 Knockout Engineered T Cells for the Treatment of Metastatic Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by 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: November 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 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.

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

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pathologically verified stage IV Renal 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02867332

Contacts
Contact: Wujiang Liu, MD and PhD 861083575825 liuwujiang@bjmu.edu.cn
Contact: Jie Jin, MD and PhD 861083575811 jinjie@vip.163.com

Sponsors and Collaborators
Peking University
Cell Biotech Co., Ltd.
Investigators
Principal Investigator: Yinglu Guo, MD Peking University First Hospital
  More Information

Publications:
Responsible Party: Yinglu Guo, Professor, Peking University
ClinicalTrials.gov Identifier: NCT02867332     History of Changes
Other Study ID Numbers: 11007965940
Study First Received: August 11, 2016
Last Updated: August 11, 2016
Individual Participant Data  
Plan to Share IPD: Undecided
Plan Description: plan to do

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Polystyrene sulfonic acid
Cyclophosphamide
Interleukin-2
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Antineoplastic Agents
Myeloablative Agonists
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on April 25, 2017