Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Clinical Trial to Evaluate the Efficacy and Safety of Epstein-Barr Virus Induced Natural T Lymphocyte(EBViNT) Cell in Patients With Progressive EBV Positive Extranodal NK/T-cell Lymphoma Where Standard Treatments Have Failed

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03789617
Recruitment Status : Recruiting
First Posted : December 28, 2018
Last Update Posted : December 31, 2018
Sponsor:
Information provided by (Responsible Party):
Eutilex

Brief Summary:

The present study is a multi-center, single-arm, open, phase I/IIa clinical trial to evaluate the efficacy and safety of EBViNT Cell when administered to patients with Epstein-Barr (EBV) positive NK/T-cell lymphoma.

The present study doubles the maximum dose of 7.0x108 cells from phase I and administers three subjects with the investigational product at 1.4x109 cells, checks the safety for 28 days after administration.


Condition or disease Intervention/treatment Phase
EBV Associated Extranodal NK/T-cell Lymphoma Biological: EBViNT Cell Phase 1 Phase 2

Detailed Description:

The present study is a multi-center, single-arm, open, phase I/IIa clinical trial to evaluate the efficacy and safety of EBViNT Cell when administered to patients with Epstein-Barr (EBV) positive NK/T-cell lymphoma.

The present study doubles the maximum dose of 7.0x10^8 cells from phase I and administers three subjects with the investigational product at 1.4x10^9 cells, checks the safety for 28 days after administration, and proceeds in accordance with the following criteria.

  • If CTCAE grade 3 or higher adverse drug events (ADR) do not occur in the three subjects: Begin enrollment for phase IIa
  • If a CTCAE grade 3 or higher ADR occurs in one of the three subjects: Enroll three more subjects (up to six subjects in total) and assess whether any CTCAE grade 3 or higher ADR occurs

    • If a CTCAE grade 3 or higher ADR does not occur in the three additional subjects (1/6): Begin enrollment for phase IIa
    • If a CTCAE grade 3 or higher ADR occurs in at least one of the three additional subjects (more than 2/6): Begin enrollment for phase IIa at 7.0x10^8 cells, the maximum dose from phase I
  • If a CTCAE grade 3 or higher ADR occurs in two of the three subjects: Begin enrollment for phase IIa at 7.0x10^8 cells, the maximum dose from phase I

Subjects participating in the present study will undergo 1) an EBV epitope screening test followed by 2) an eligibility assessment for clinical trial enrollment.

Subjects who are administered with the investigational product will be monitored until progressive disease (PD) is confirmed or for 24 weeks (main observation period of 4 weeks + monitoring for 20 weeks) to evaluate the product's safety and efficacy, and will undergo immunological assessment.

Radiological tests for tumor assessment will be conducted at the enrollment visit, 4 weeks, 8 weeks, 16 weeks, and 24 weeks and assessed by the Independent Radiology Review Committee (IRRC) using the Lugano criteria. To eliminate pseudo-progression, progressive disease (PD) will be determined by considering immunological tests, a quantitative EBV DNA assay, and intermediate response (IR) under LYRIC. Biopsies may be performed to achieve this.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-center, Single-arm, Open, Phase I/IIa Clinical Trial to Evaluate the Efficacy and Safety of EBViNT Cell (EBV Latent Membrane Protein-2a [LMP2A] Specific Eutil Autologous Blood-derived T Lymphocytes) in Patients With Progressive Epstein-Barr Virus (EBV) Positive Extranodal NK/T-cell Lymphoma Where Standard Treatments Have Failed
Actual Study Start Date : December 14, 2018
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: EBViNT Cell Biological: EBViNT Cell
  1. Dosage: 1 bag containing 1.4x10^9 cells/100mL
  2. Administration: Inject intravenously over 30 minutes
  3. Dosing schedule: Single dose
Other Name: Eutil autologous blood-derived T lymphocytes




Primary Outcome Measures :
  1. Confirmed objective response rate (confirmed ORR) [assessed by IRRC] [ Time Frame: up to 6 month from LPI ]

Secondary Outcome Measures :
  1. Duration of response (DoR) [assessed by IRRC and investigator] [ Time Frame: up to 6 month from LPI ]
  2. Disease control rate (DCR) [assessed by IRRC and investigator] [ Time Frame: up to 6 month from LPI ]
  3. Objective response rate (ORR) [assessed by investigator] [ Time Frame: up to 6 month from LPI ]
  4. Complete response rate (CR rate) [assessed by IRRC and investigator] [ Time Frame: up to 6 month from LPI ]
  5. Partial response rate (PR rate) [assessed by IRRC and investigator] [ Time Frame: up to 6 month from LPI ]
  6. Partial response duration (PR duration) [assessed by IRRC and investigator] [ Time Frame: up to 6 month from LPI ]
  7. Progression-free survival (PFS) [ Time Frame: up to 6 month from LPI ]
  8. Overall survival (OS) [ Time Frame: up to 6 month from LPI ]

Other Outcome Measures:
  1. Immunological assessment [ Time Frame: up to 6 month ]
    Plasma cytokine analysis (IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, TNF, IFN-γ, IL-17a) EBV LMP2a-specific cytokine production (IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, TNF, IFN-γ, IL-17a) Phenotypical analysis of CD8 T cells

  2. Quantitative EBV DNA assay [ Time Frame: up to 6 month ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. At least 19 years of age
  2. Patients who have been diagnosed with histologically confirmed extranodal NK/T-cell lymphoma (ENKTL) as per WHO classification, and who have been found to be positive for EBV encoded RNA (EBER) by in situ hybridization (ISH) (previous test results may be used as evidence if available)
  3. Persons who have recurred or progressed after one or two asparaginase-based chemotherapy regimens
  4. Performance status of 0, 1, or 2 on the ECOG performance status scale
  5. Patients with an expected survival of at least 12 weeks
  6. Patients who have consented to the use of accepted methods of contraception for the duration of the present study (E.g., surgical sterilization of self or partner, intrauterine contraceptive device, barrier contraceptives, combined use of diaphragms or condoms)
  7. Patients who have given written consent to voluntarily participate in the present study

Enrollment Criteria (Visit 2)

  1. Persons who have passed the epitope screening test and who have been found to be capable of production
  2. Persons with appropriate liver, renal, and bone marrow function (two retests are permitted for borderline results, and corrections such as transfusions to meet the requirements are permitted)

    1. Absolute neutrophil count (ANC) more than 1,000/mm3
    2. Platelet count more than 75,000/μL
    3. Serum creatinine less than 2.0 mg/dL
    4. AST and/or ALT less than 3 x upper limit of normal range (ULN)
    5. Total bilirubin less than 2.0 mg/dL

Exclusion Criteria:

  1. Where central nervous system (CNS) lymphoma or uncontrolled CNS metastasis is present (patients with brain metastasis that has been treated and is stable [stable for at least 30 days based on radiology records] may be enrolled)
  2. Patients with aggressive NK cell leukemia
  3. Patients with hemophagocytic lymphohistiocytosis (HLH)
  4. Persons who have previously received a solid organ transplant
  5. Persons who have received surgery, radiotherapy, or chemotherapy in the 3 weeks prior to screening for the present study
  6. Persons who have been administered any other investigational product in the 3 weeks prior to screening for the present study
  7. Persons who have not recovered from the toxicity of any previous treatment to Grade 1 or lower based on NCI CTCAE v5.0
  8. Patients in whom a tuberculosis infection was confirmed in the 1 year prior to screening for the present study
  9. Patients who have received immunosuppressants, including steroids, in the 3 weeks prior to screening (local steroids and steroid inhalers are permitted, and steroid equivalent to 20 mg/day of prednisolone may be administered at the investigator's discretion)
  10. Persons who have been diagnosed with a malignant tumor other than the target disease in the past 5 years (treated basal cell carcinoma, squamous epithelial cell carcinoma, and non-invasive cervical cancer do not necessitate exclusion)
  11. Patients with the following (but not limited to) clinically significant cardiovascular comorbidities as determined by the investigator

    : Uncontrolled hypertension (i.e., systolic pressure > 180 mmHg and/or diastolic pressure > 100 mm/Hg), unstable angina, pulmonary embolism, cerebrovascular disease, valvular disease, congestive heart failure (NYHA severity classification Grade III or IV), or myocardial infarction or serious cardiac arrhythmia within the 24 weeks prior to screening

  12. Patients with any other serious medical disease that may interfere with treatment by the investigational product
  13. Pregnant or lactating women
  14. Where there is psychiatric history that may compromise compliance with the protocol
  15. Patients who test positive for anti-HIV antibodies
  16. Patients deemed unsuitable to participate in the clinical trial by an investigator based on active infection (HBV, HCV) test results
  17. Patients with findings of autoimmune or inflammatory disease, whose abnormal results from an autoimmune response test have been deemed clinically significant by an investigator
  18. Patients deemed unsuitable to participate in the present study by an investigator due to comorbidities other than the above
  19. Patients who are unsuitable to participate in the present study due to the production period and nature of the investigational product

Information from the National Library of Medicine

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): NCT03789617


Contacts
Layout table for location contacts
Contact: Eric(Backhwan) Lee 82234027317 eric1224@eutilex.com

Locations
Layout table for location information
Korea, Republic of
Samsung Medical Center Not yet recruiting
Seoul, Gangnam-gu, Korea, Republic of, 06351
Contact: Won Seog Kim, Dr    82221487390      
National Cancer Center Recruiting
Goyang-si, Gyeonggi-do, Korea, Republic of, 10408
Contact: Hyeon Seok Eom, Dr    82319201165      
Sponsors and Collaborators
Eutilex
Investigators
Layout table for investigator information
Principal Investigator: Hyeon Seok Eom, MD National Cancer Center
Principal Investigator: Won Seog Kim, MD Samsung Medical Center
Principal Investigator: Seok-Goo Cho, MD The Catholic Univ. of Korea Seoul St. Mary's Hospital
Principal Investigator: Joon Ho Moon, MD Kyungpook National University
Principal Investigator: Ho Jin Shin, MD Pusan National University Hospital
Principal Investigator: Dok Hyun Yoon, MD Asan Medical Cente
Principal Investigator: Won Sik Lee, MD Inje University
Principal Investigator: Deok-Hwan Yang, MD Chonnam National University Hospital

Additional Information:
Publications:
Layout table for additonal information
Responsible Party: Eutilex
ClinicalTrials.gov Identifier: NCT03789617     History of Changes
Other Study ID Numbers: EBViNT
First Posted: December 28, 2018    Key Record Dates
Last Update Posted: December 31, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eutilex:
Cytotoxic T cell
Lymphoma
Immuno-oncology
ENKTL
EBViNT
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Lymphoma, T-Cell
Lymphoma, Extranodal NK-T-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin