Clinical trial · Interventional
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
NCT03044743CI-TRIAL-00027315unknownPhase 1 / Phase 2ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (5)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Stage IV Adult Hodgkin Lymphoma | Adult Hodgkin Lymphoma | CURATED_BROADER | 0.78 |
| Stage IV Diffuse Large B-Cell Lymphoma | Diffuse Large B-Cell Lymphoma | CURATED_BROADER | 0.80 |
| Stage IV Gastric Carcinoma | Gastric Carcinoma | CURATED_BROADER | 0.78 |
| Stage IV Nasopharyngeal Carcinoma | Nasopharyngeal Carcinoma | CURATED_BROADER | 0.78 |
| T-Cell Lymphoma Stage IV | T-Cell Non-Hodgkin Lymphoma | CURATED_BROADER | 0.78 |
Interventions
Interventions (3)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Cyclophosphamide | Drug | Cyclophosphamide | ALIAS |
| Fludarabine | Drug | Fludarabine | ALIAS |
| Interleukin-2 | Drug | Aldesleukin | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- 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.
- interventionNames
- Drug: Fludarabine
- Drug: Cyclophosphamide
- Drug: Interleukin-2
Primary outcomes (1)
- measure
- Number of participants with Adverse Events using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in patients
- timeFrame
- 6 months
Secondary outcomes (6)
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 75 Years
Show eligibility criteria text
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
References
Publications (6)
- BACKGROUNDKim 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 25254613
- BACKGROUNDQuan 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 26361042
- BACKGROUNDLouis 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 20948438
- BACKGROUNDLloyd 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 23935598
- BACKGROUNDSu 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 26818188
- BACKGROUNDMali 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 24076990