PD-1 Knockout EBV-CTLs for Advanced Stage Epstein-Barr Virus (EBV) Associated Malignancies

April 28, 2017 updated by: Yang Yang

A Phase I/II Trial of PD-1 Knockout EBV-CTLs for Advanced Stage EBV Associated Malignancies

This study will evaluate the safety of PD-1 knockout EBV-CTL cells in treating EBV (Epstein-Barr virus) positive advanced stage malignancies. Blood samples will also be collected for research purposes.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

This is a study of CRISPR-Cas9 mediated PD-1 knockout-T cells from autologous origin. Patients are assigned to receive 4 circles of cell therapy. The safety and clinical response are evaluated. Biomarkers and immunological markers are also monitored.

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Jiangsu
      • Nanjing, Jiangsu, China, 210008
        • Recruiting
        • The Comprehensive Cancer Center of Nanjing Drum Tower Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Pathologically verified stage IV gastric carcinoma, nasopharyngeal carcinoma and lymphoma with measurable lesions (At least one measurable lesion or the immunotherapy)
  • Pathologically verified as EBV positive malignancies
  • Human leukocyte antigen (HLA) genotypes: HLA-A02, HLA-A24 or HLA-A11 genotypes
  • Progressed after standard treatment or the patients refused to accept the standard treatment
  • Performance score: 0-1
  • Expected life span: >= 3 months
  • Toxicities from prior treatment has resolved. Washout period is 1 months
  • Major organs function normally
  • Women at pregnant ages should be under contraception
  • Willing and able to provide informed consent

Exclusion Criteria:

  • Patients with possible drug allergy of immunotherapy
  • Patients with active bacterial or fungal infections
  • Coagulopathy, or ongoing thrombolytics and/or anticoagulation
  • Blood-borne infectious disease, e.g. hepatitis B, hepatitis C and HIV
  • History of coronary artery disease, asthma, or vascular disease or other disease inappropriate for treatment deemed by treating physician
  • With other tumors except for in situ cervical cancer, treated squamous cell carcinoma and bladder cancer (Ta and TIS) or other malignancies that have been treated with radical therapy (at least for 5 years before the enrollment)
  • With other immune diseases, or chronic use of immunosuppressants or steroids
  • Pregnant and lactating women
  • Compliance cannot be expected
  • Other conditions requiring exclusion deemed by physician

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: PD-1 knockout EBV-CTL

Peripheral blood lymphocytes will be collected and Programmed cell death protein 1(PDCD1) gene will be knocked out by CRISP-Cas9 system and EBV-CTL will be generated in the laboratory (PD-1 Knockout EBV-CTL).

Fludarabine at 30mg/m2 and Cyclophosphamide at 300mg/m2 single dose will be administered 3 days i.v. before cell infusion.

A total of 2 x 10^7/kg PD-1 Knockout CTL 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 daily( iv) since the first day of the cell infusion for 5 consecutive days, 4000,000 international unit（IU）/day . Patients will receive a total of four cycles of treatment.
Drug: Fludarabine
To modify immune micro-environment
Other Names:
  • Fludara
Drug: Cyclophosphamide
To modify immune micro-environment
Other Names:
  • Cytoxan
Drug: Interleukin-2
To sustain the survival of infused T cells
Other Names:
  • IL-2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of participants with Adverse Events using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in patients
Time Frame: 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall Survival (OS)
Time Frame: up to 3 years
up to 3 years
Response Rate
Time Frame: 90 days
90 days
Progression free survival (PFS)
Time Frame: up to 1 year
up to 1 year
The duration of the normalization of tumor marker
Time Frame: up to 3 years
up to 3 years
Interferon-γ change of T cells in the peripheral blood stimulated by tumor antigens
Time Frame: Baseline and 1 month, 3 months and 6 months
Baseline and 1 month, 3 months and 6 months
Th1/Th2 change in the peripheral blood
Time Frame: Baseline and 1 month, 3 months and 6 months
Baseline and 1 month, 3 months and 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yang Yang

Investigators

  • Principal Investigator: Baorui Liu, MD, The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

April 7, 2017

Primary Completion (ANTICIPATED)

March 1, 2020

Study Completion (ANTICIPATED)

March 1, 2022

Study Registration Dates

First Submitted

January 22, 2017

First Submitted That Met QC Criteria

February 6, 2017

First Posted (ESTIMATE)

February 7, 2017

Study Record Updates

Last Update Posted (ACTUAL)

May 2, 2017

Last Update Submitted That Met QC Criteria

April 28, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PD-1-KO-EBV-CTL

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Stage IV Adult Hodgkin Lymphoma

Clinical Trials on Fludarabine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Burkina Faso

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe