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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Extranodal NK/T-cell Lymphoma
• Intervention / Treatment: Biological: VT-EBV-N; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 48
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dae-Hee Sohn; Phone Number: 82-70-4348-7527; Email: goriest@vigencell.com
• Study Contact Backup: Name: Hyun-Jung Sohn; Phone Number: 82-70-4348-7527; Email: sohnhj@vigencell.com

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of, 47392
    • Recruiting
    • Inje University Busan Paik Hospital
    • Contact: Won-Sik Lee, M.D., Ph.D
  • Daegu, Korea, Republic of, 41931
    • Recruiting
    • Keimyung University Daegu Dongsan Hospital
    • Contact: YoungRok Do, M.D., Ph.D
  • Gyeonggi-do, Korea, Republic of, 14068
    • Recruiting
    • Hallym Univ. Medical Center
    • Contact: Hyo Jung Kim, M.D., Ph.D
  • Hwasun, Korea, Republic of, 58128
    • Recruiting
    • Chonnam National University Hwasun Hospital
    • Contact: Deok-Hwan Yang, M.D., Ph.D
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
    • Contact: Inho Kim, M.D., Ph.D
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Severance Hospital
    • Contact: Jinseok Kim, M.D., Ph.D
  • Seoul, Korea, Republic of, 05030
    • Recruiting
    • Konkuk University Medical Center
    • Contact: Sung-Yong Kim, M.D., Ph.D
  • Seoul, Korea, Republic of, KS013
    • Recruiting
    • Seoul St.Mary's Hospital
    • Contact: Seok-Goo Cho, M.D., Ph.D)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. EBV positive extranodal NK/T cell lymphoma (ENKL) patients pathologically confirmed according to WHO classification at first diagnosis
2. 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
3. 19 years and above to 75 years and below
4. Patients with ECOG performance criteria score of 0 to 2
5. Patients with acceptable hematopoietic function (ANC ≥ 1.5 x 109 /L, PLT ≥ 100 x 109 /L, Hb ≥ 9 g/dL)
6. Patients with acceptable liver function (total bilirubin < 2 x upper limit of normal, AST/ALT < 3 x upper limit of normal)
7. Patients with renal function of eGFR > 50 or better
8. Patients with life expectancy of 6 or longer
9. 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.)
10. Patients who have voluntarily given written consent to participate in this study

Exclusion Criteria:

1. Other pathological classifications of nasal cavity lymphoma than ENKL at initial diagnosis
2. Patients with ENKL that has invaded the central nervous system
3. Patients in PR, SD or PD state, not complete remission (CR)
4. Patients who cannot generate EBV-CTL
5. Patients who have received allogeneic stem cell transplantations
6. 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)
7. Patients with apparent infection (HIV infection, chronic hepatitis B, chronic hepatitis C, active tuberculosis, etc.)
8. Patients with malignant tumors or previous history of malignant tumors except completely recovered non-melanoma skin cancer or stage 0 (in situ) cervical carcinoma
9. Patients currently receiving treatment for ENKL such as chemotherapy, hormone therapy, or immunotherapy
10. Patients with hypersensitivity to the investigational product or pretreatment products, including cryoprotectants

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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) ~

Collaborators and Investigators

• Sponsor: ViGenCell Inc.
• Investigators: Principal Investigator: Seok-Goo Cho, The Catholic University of Korea

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2019
• Primary Completion (Anticipated): December 4, 2023
• Study Completion (Anticipated): June 3, 2024

Study Registration Dates

• First Submitted: September 12, 2018
• First Submitted That Met QC Criteria: September 12, 2018
• First Posted (Actual): September 14, 2018

Study Record Updates

• Last Update Posted (Actual): April 29, 2022
• Last Update Submitted That Met QC Criteria: April 28, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, Extranodal NK-T-Cell
• Other Study ID Numbers: VT-EBV-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No