VT-EBV-N for Treatment of Severe in EBV Positive Extranodal NK/T Cell Lymphoma Patients

Study Overview
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Brief Summary
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The study aims to evaluate the efficacy and safety of VT-EBV-N (EBV-CTL) administration in ENKL patients after complete remission (CR). This is to prove the effect of VT-EBV-N (EBV-CTL) in prevention of ENKL relapse compared to placebo, by checking the primary endpoint of DFS rate (disease free survival, no relapse or death after randomization) at 2 years (103 weeks) for the last subject enrolled. 50% of the subjects will be administered VT-EBV-N (EBV-CTL), while the remaining subjects will be administered a placebo.

Detailed Description
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NK/T-cell lymphoma is a malignant tumor originating in NK cells and T lymphocytes. ENKL is associated with Epstein-Barr virus (EBV) infection and typically occurs in the nasal area, being termed ENKL, nasal type.EBV is a common virus in the herpes family. EBV infection in patients with lowered immunity such as those with Acquired Immune Deficiency Syndrome or those taking immunosuppressants after bone marrow transplant may induce lymphoproliferative diseases or cancer. VT-EBV-N (EBV-CTL) is a cytotoxicity T lymphocyte (CTL) targeting EBV expressed tumor cells indicated for ENKL. Antigen-presenting cells derived from the patient's own blood is used to activate T-cells in a test tube to recognize EBV, which are then expanded in vitro and infused into the patient's body. Targeted immunotherapy using EBV-CTL is a safe form of treatment that can improve long-term disease-free survival rates by boosting antitumor immunity without affecting other tissues apart from tumor cells.

Official Title
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A Phase 2 Study to Evaluate the Efficacy and Safety of Postremission Therapy Using VT-EBV-N in EBV Positive Extranodal NK/T Cell Lymphoma Patients

Conditions
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Extranodal NK/T-cell Lymphoma

Intervention / Treatment
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* Biological: VT-EBV-N
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: EBV positive extranodal NK/T cell lymphoma (ENKL) patients pathologically confirmed according to WHO classification at first diagnosis Patients whose complete remission (CR) has been confirmed within 6 months before screening and maintained, presenting high risk of relapse due to one or more of the following 1) Patients who are EBV detectable at initial diagnosis, with one or more of the following high risk factors 60 years of age or older, Ann Arbor stage II   IV, non-nasal type disease, local invasiveness (defined with T3 or T4), elevated LDH (> upper limit of normal)) 2) Patients confirmed to have EBV DNAemia (> 2000 copies/ml) during or after treatment 3) Patients who achieved remission from secondary or greater remission induction therapy after the failure of primary remission induction, or achieved remission after relapse 19 years and above to 75 years and below Patients with ECOG performance criteria score of 0 to 2 Patients with acceptable hematopoietic function (ANC ≥ 1.5 x 109 /L, PLT ≥ 100 x 109 /L, Hb ≥ 9 g/dL) Patients with acceptable liver function (total bilirubin < 2 x upper limit of normal, AST/ALT < 3 x upper limit of normal) Patients with renal function of eGFR > 50 or better Patients with life expectancy of 6 or longer Patients who have agreed to use two different types of birth control during the study period (Females of childbearing age or within 2 years after menopause have to show negative results in urine pregnancy test) (E.g., dual contraception using oral contraceptives, contraceptive implant, contraceptive injection, or contraceptive patch combined with intrauterine device, spermicide foam or gel, contraceptive film, vaginal diaphragm, cervical cap, condom, etc.) Patients who have voluntarily given written consent to participate in this study Exclusion Criteria: Other pathological classifications of nasal cavity lymphoma than ENKL at initial diagnosis Patients with ENKL that has invaded the central nervous system Patients in PR, SD or PD state, not complete remission (CR) Patients who cannot generate EBV-CTL Patients who have received allogeneic stem cell transplantations Patients with severe or uncontrolled medical disorders(diabetes exceeding HbA1C9%, severe hypertension exceeding 180/110 mmHg, heart failure of NYHA class Ⅲ or Ⅳ, myocardial infarction diagnosed within 6 months prior to screening) Patients with apparent infection (HIV infection, chronic hepatitis B, chronic hepatitis C, active tuberculosis, etc.) Patients with malignant tumors or previous history of malignant tumors except completely recovered non-melanoma skin cancer or stage 0 (in situ) cervical carcinoma Patients currently receiving treatment for ENKL such as chemotherapy, hormone therapy, or immunotherapy Patients with hypersensitivity to the investigational product or pretreatment products, including cryoprotectants

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VT-EBV-N<br>Epstein-barr virus human cytotoxic T lymphocytes (EBV-CTL) | Biological: VT-EBV-N<br>* Epstein-barr virus human cytotoxic T lymphocytes (EBV-CTL)<br>|
| Placebo Comparator: Placebo<br>Peripheral blood mononuclear cell, PBMC | Other: Placebo<br>* Peripheral blood mononuclear cell, PBMC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| No relapse or death due to any reason after randomization |  | Randomization (8 weeks before administration)   116 weeks after treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| No death after randomization |  | Randomization (8 weeks before administration)   116 weeks after treatment period | 
| No relapse or death due to any reason after randomization |  | Randomization (116 weeks after treatment period)   |