Stage IV Adult Hodgkin Lymphoma, Stage IV Diffuse Large B-Cell Lymphoma, Stage IV Gastric Carcinoma, Stage IV Nasopharyngeal Carcinoma, T-Cell Lymphoma Stage IV
Conditions
Keywords
PD-1, CRISPR Cas9, EBV, advanced stage 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.
Interventions
DRUGFludarabine
To modify immune micro-environment
DRUGCyclophosphamide
To modify immune micro-environment
DRUGInterleukin-2
To sustain the survival of infused T cells
Sponsors
Yang Yang
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants with Adverse Events using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in patients | 6 months |
Secondary
| Measure | Time frame |
|---|---|
| Progression free survival (PFS) | up to 1 year |
| Overall Survival (OS) | up to 3 years |
| Response Rate | 90 days |
| Interferon-γ change of T cells in the peripheral blood stimulated by tumor antigens | Baseline and 1 month, 3 months and 6 months |
| Th1/Th2 change in the peripheral blood | Baseline and 1 month, 3 months and 6 months |
| The duration of the normalization of tumor marker | up to 3 years |
Countries
China
Contacts
Primary ContactBaorui Liu, MD
Backup ContactShu Su, MD
Outcome results
None listed