PD-1 Knockout EBV-CTLs for Advanced Stage Epstein-Barr Virus (EBV) Associated Malignancies
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ClinicalTrials.gov Identifier: NCT03044743 |
Recruitment Status : Unknown
Verified April 2017 by Yang Yang, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School.
Recruitment status was: Recruiting
First Posted : February 7, 2017
Last Update Posted : May 2, 2017
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
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 | Drug: Fludarabine Drug: Cyclophosphamide Drug: Interleukin-2 | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 20 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase I/II Trial of PD-1 Knockout EBV-CTLs for Advanced Stage EBV Associated Malignancies |
Actual Study Start Date : | April 7, 2017 |
Estimated Primary Completion Date : | March 2020 |
Estimated Study Completion Date : | March 2022 |
Arm | Intervention/treatment |
---|---|
Experimental: 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. |
Drug: Fludarabine
To modify immune micro-environment
Other Name: Fludara Drug: Cyclophosphamide To modify immune micro-environment
Other Name: Cytoxan Drug: Interleukin-2 To sustain the survival of infused T cells
Other Name: IL-2 |
- Number of participants with Adverse Events using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in patients [ Time Frame: 6 months ]
- Response Rate [ Time Frame: 90 days ]
- Progression free survival (PFS) [ Time Frame: up to 1 year ]
- Overall Survival (OS) [ Time Frame: up to 3 years ]
- The duration of the normalization of tumor marker [ Time Frame: up to 3 years ]
- 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 ]
- Th1/Th2 change in the peripheral blood [ Time Frame: Baseline and 1 month, 3 months and 6 months ]
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Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03044743
Contact: Baorui Liu, MD | 0086-25-83106666-61331 | baoruiliu07@163.com | |
Contact: Shu Su, MD | 0086-25-83106666-61331 | ssnine@126.com |
China, Jiangsu | |
The Comprehensive Cancer Center of Nanjing Drum Tower Hospital | Recruiting |
Nanjing, Jiangsu, China, 210008 | |
Contact: Yang Yang, MD,PhD,MSCR 0086-18602568379 wing_young7@hotmail.com | |
Contact: Jing Yan, MD 0086-15805182426 firefreebird@163.com | |
The Comprehensive Cancer Center of Nanjing Drum Tower Hospital | Recruiting |
Nanjing, Jiangsu, China, 210008 | |
Contact: Yang Yang 18602568379 wing_young7@hotmail.com |
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 |
Responsible Party: | Yang Yang, MD, PhD, MSCR, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School |
ClinicalTrials.gov Identifier: | NCT03044743 |
Other Study ID Numbers: |
PD-1-KO-EBV-CTL |
First Posted: | February 7, 2017 Key Record Dates |
Last Update Posted: | May 2, 2017 |
Last Verified: | April 2017 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Undecided |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
PD-1 CRISPR Cas9 EBV advanced stage malignancies |
Lymphoma Carcinoma Neoplasms Hodgkin Disease Lymphoma, Large B-Cell, Diffuse Nasopharyngeal Carcinoma Stomach Neoplasms Neoplasms by Histologic Type Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Neoplasms, Glandular and Epithelial Lymphoma, B-Cell Lymphoma, Non-Hodgkin |
Nasopharyngeal Neoplasms Pharyngeal Neoplasms Otorhinolaryngologic Neoplasms Head and Neck Neoplasms Neoplasms by Site Nasopharyngeal Diseases Pharyngeal Diseases Stomatognathic Diseases Otorhinolaryngologic Diseases Gastrointestinal Neoplasms Digestive System Neoplasms Digestive System Diseases Gastrointestinal Diseases Stomach Diseases Cyclophosphamide |