Clinical Trials /

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

NCT03044743

Description:

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.

Related Conditions:
  • Gastric Carcinoma
  • Lymphoma
  • Nasopharyngeal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: PD-1 Knockout EBV-CTLs for Advanced Stage Epstein-Barr Virus (EBV) Associated Malignancies
  • Official Title: A Phase I/II Trial of PD-1 Knockout EBV-CTLs for Advanced Stage EBV Associated Malignancies

Clinical Trial IDs

  • ORG STUDY ID: PD-1-KO-EBV-CTL
  • NCT ID: NCT03044743

Conditions

  • Stage IV Gastric Carcinoma
  • Stage IV Nasopharyngeal Carcinoma
  • T-Cell Lymphoma Stage IV
  • Stage IV Adult Hodgkin Lymphoma
  • Stage IV Diffuse Large B-Cell Lymphoma

Interventions

DrugSynonymsArms
FludarabineFludaraPD-1 knockout EBV-CTL
CyclophosphamideCytoxanPD-1 knockout EBV-CTL
Interleukin-2IL-2PD-1 knockout EBV-CTL

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
PD-1 knockout EBV-CTLExperimentalPeripheral 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.
  • Fludarabine
  • Cyclophosphamide
  • Interleukin-2

Eligibility Criteria

        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
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

Measure:Response Rate
Time Frame:90 days
Safety Issue:
Description:
Measure:Progression free survival (PFS)
Time Frame:up to 1 year
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:up to 3 years
Safety Issue:
Description:
Measure:The duration of the normalization of tumor marker
Time Frame:up to 3 years
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Th1/Th2 change in the peripheral blood
Time Frame:Baseline and 1 month, 3 months and 6 months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Yang Yang

Trial Keywords

  • PD-1
  • CRISPR Cas9
  • EBV
  • advanced stage malignancies

Last Updated

April 28, 2017