PD-1 Knockout EBV-CTLs for Advanced Stage Epstein-Barr Virus (EBV) Associated Malignancies
NCT ID: NCT03044743
Last Updated: 2017-05-02
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE1/PHASE2
20 participants
INTERVENTIONAL
2017-04-07
2022-03-31
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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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.
Fludarabine
To modify immune micro-environment
Cyclophosphamide
To modify immune micro-environment
Interleukin-2
To sustain the survival of infused T cells
Interventions
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Fludarabine
To modify immune micro-environment
Cyclophosphamide
To modify immune micro-environment
Interleukin-2
To sustain the survival of infused T cells
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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 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
18 Years
75 Years
ALL
No
Sponsors
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Yang Yang
OTHER
Responsible Party
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Yang Yang
MD, PhD, MSCR
Principal Investigators
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Baorui Liu, MD
Role: PRINCIPAL_INVESTIGATOR
The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University
Locations
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The Comprehensive Cancer Center of Nanjing Drum Tower Hospital
Nanjing, Jiangsu, China
The Comprehensive Cancer Center of Nanjing Drum Tower Hospital
Nanjing, Jiangsu, China
Countries
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Central Contacts
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Facility Contacts
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References
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Kim SY, Park C, Kim HJ, Park J, Hwang J, Kim JI, Choi MG, Kim S, Kim KM, Kang MS. Deregulation of immune response genes in patients with Epstein-Barr virus-associated gastric cancer and outcomes. Gastroenterology. 2015 Jan;148(1):137-147.e9. doi: 10.1053/j.gastro.2014.09.020. Epub 2014 Sep 22.
Quan L, Chen X, Liu A, Zhang Y, Guo X, Yan S, Liu Y. PD-1 Blockade Can Restore Functions of T-Cells in Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma In Vitro. PLoS One. 2015 Sep 11;10(9):e0136476. doi: 10.1371/journal.pone.0136476. eCollection 2015.
Louis CU, Straathof K, Bollard CM, Ennamuri S, Gerken C, Lopez TT, Huls MH, Sheehan A, Wu MF, Liu H, Gee A, Brenner MK, Rooney CM, Heslop HE, Gottschalk S. Adoptive transfer of EBV-specific T cells results in sustained clinical responses in patients with locoregional nasopharyngeal carcinoma. J Immunother. 2010 Nov-Dec;33(9):983-90. doi: 10.1097/CJI.0b013e3181f3cbf4.
Lloyd A, Vickery ON, Laugel B. Beyond the antigen receptor: editing the genome of T-cells for cancer adoptive cellular therapies. Front Immunol. 2013 Aug 5;4:221. doi: 10.3389/fimmu.2013.00221. eCollection 2013.
Su S, Hu B, Shao J, Shen B, Du J, Du Y, Zhou J, Yu L, Zhang L, Chen F, Sha H, Cheng L, Meng F, Zou Z, Huang X, Liu B. CRISPR-Cas9 mediated efficient PD-1 disruption on human primary T cells from cancer patients. Sci Rep. 2016 Jan 28;6:20070. doi: 10.1038/srep20070.
Mali P, Esvelt KM, Church GM. Cas9 as a versatile tool for engineering biology. Nat Methods. 2013 Oct;10(10):957-63. doi: 10.1038/nmeth.2649.
Other Identifiers
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PD-1-KO-EBV-CTL
Identifier Type: -
Identifier Source: org_study_id
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