Description:
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.
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
PD-1-KO-EBV-CTL
- NCT ID:
NCT03044743
Conditions
- Stage IV Gastric Carcinoma
- Stage IV Nasopharyngeal Carcinoma
- T-Cell Lymphoma Stage IV
- Stage IV Adult Hodgkin Lymphoma
- Stage IV Diffuse Large B-Cell Lymphoma
Interventions
Drug | Synonyms | Arms |
---|
Fludarabine | Fludara | PD-1 knockout EBV-CTL |
Cyclophosphamide | Cytoxan | PD-1 knockout EBV-CTL |
Interleukin-2 | IL-2 | PD-1 knockout EBV-CTL |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
PD-1 knockout EBV-CTL | Experimental | 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
- Cyclophosphamide
- Interleukin-2
|
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
Maximum Eligible Age: | 75 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of participants with Adverse Events using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in patients |
Time Frame: | 6 months |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Response Rate |
Time Frame: | 90 days |
Safety Issue: | |
Description: | |
Measure: | Progression free survival (PFS) |
Time Frame: | up to 1 year |
Safety Issue: | |
Description: | |
Measure: | Overall Survival (OS) |
Time Frame: | up to 3 years |
Safety Issue: | |
Description: | |
Measure: | The duration of the normalization of tumor marker |
Time Frame: | up to 3 years |
Safety Issue: | |
Description: | |
Measure: | Interferon-γ change of T cells in the peripheral blood stimulated by tumor antigens |
Time Frame: | Baseline and 1 month, 3 months and 6 months |
Safety Issue: | |
Description: | |
Measure: | Th1/Th2 change in the peripheral blood |
Time Frame: | Baseline and 1 month, 3 months and 6 months |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Yang Yang |
Trial Keywords
- PD-1
- CRISPR Cas9
- EBV
- advanced stage malignancies
Last Updated
May 2, 2017