PD-1 Knockout EBV-CTLs for Advanced Stage Epstein-Barr Virus (EBV) Associated Malignancies
A Phase I/II Trial of PD-1 Knockout EBV-CTLs for Advanced Stage EBV Associated Malignancies
1 other identifier
interventional
20
1 country
2
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Apr 2017
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 22, 2017
CompletedFirst Posted
Study publicly available on registry
February 7, 2017
CompletedStudy Start
First participant enrolled
April 7, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2022
CompletedMay 2, 2017
April 1, 2017
2.9 years
January 22, 2017
April 28, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of participants with Adverse Events using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in patients
6 months
Secondary Outcomes (6)
Response Rate
90 days
Progression free survival (PFS)
up to 1 year
Overall Survival (OS)
up to 3 years
The duration of the normalization of tumor marker
up to 3 years
Interferon-γ change of T cells in the peripheral blood stimulated by tumor antigens
Baseline and 1 month, 3 months and 6 months
- +1 more secondary outcomes
Study Arms (1)
PD-1 knockout EBV-CTL
EXPERIMENTALPeripheral 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.
Interventions
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Yang Yanglead
Study Sites (2)
The Comprehensive Cancer Center of Nanjing Drum Tower Hospital
Nanjing, Jiangsu, 210008, China
The Comprehensive Cancer Center of Nanjing Drum Tower Hospital
Nanjing, Jiangsu, 210008, China
Related Publications (6)
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.
PMID: 25254613BACKGROUNDQuan 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.
PMID: 26361042BACKGROUNDLouis 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.
PMID: 20948438BACKGROUNDLloyd 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.
PMID: 23935598BACKGROUNDSu 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.
PMID: 26818188BACKGROUNDMali 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.
PMID: 24076990BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- 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
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- MD, PhD, MSCR
Study Record Dates
First Submitted
January 22, 2017
First Posted
February 7, 2017
Study Start
April 7, 2017
Primary Completion
March 1, 2020
Study Completion
March 1, 2022
Last Updated
May 2, 2017
Record last verified: 2017-04