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 Information
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
Administrative Informations
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