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

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

Brief Summary

      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.
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional

Primary Outcome

Number of participants with Adverse Events using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in patients

Secondary Outcome

 Response Rate

Condition

Stage IV Gastric Carcinoma

Intervention

Fludarabine

Study Arms / Comparison Groups

 PD-1 knockout EBV-CTL

Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

20

Start Date

April 7, 2017

Completion Date

March 2022

Primary Completion Date

March 2020

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
      

Gender

All

Ages

18 Years - 75 Years

Accepts Healthy Volunteers

No

Contacts

Baorui Liu, MD, 0086-25-83106666-61331, [email protected]

Location Countries

China

Location Countries

China

NCT ID

NCT03044743

Organization ID

PD-1-KO-EBV-CTL

Responsible Party

Sponsor-Investigator

Study Sponsor

Yang Yang

Study Sponsor

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

Verification Date

April 2017