Clinical Trials /

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

NCT03789617

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 7.0x108 cells from phase I and administers three subjects with the investigational product at 1.4x109 cells, checks the safety for 28 days after administration.

Related Conditions:
  • Nasal Type Extranodal NK/T-Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Multi-center, Single-arm, Open, Phase I/IIa Clinical Trial to Evaluate the Effectiveness and Safety of EBViNT Cell (EBV Latent Membrane Protein-2a [LMP2A] in Patients With Progressive Epstein-Barr Virus (EBV) Positive Extranodal NK/T-cell Lymphoma Where Standard Treatments Have Failed
  • Official Title: A Multi-center, Single-arm, Open, Phase I/IIa Clinical Trial to Evaluate the Effectiveness 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

Clinical Trial IDs

  • ORG STUDY ID: EBViNT
  • NCT ID: NCT03789617

Conditions

  • EBV Associated Extranodal NK/T-cell Lymphoma

Interventions

DrugSynonymsArms
EBViNT CellEutil autologous blood-derived T lymphocytesEBViNT Cell

Purpose

The present study is a multi-center, single-arm, open, phase I/IIa clinical trial to evaluate the effectiveness 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.

Detailed Description

      The present study is a multi-center, single-arm, open, phase I/IIa clinical trial to evaluate
      the effectiveness 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 (2014) 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.
    

Trial Arms

NameTypeDescriptionInterventions
EBViNT CellExperimental
  • EBViNT Cell

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Confirmed objective response rate (confirmed ORR) [assessed by IRRC]
Time Frame:up to 6 month from LPI
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Duration of response (DoR) [assessed by IRRC and investigator]
Time Frame:up to 6 month from LPI
Safety Issue:
Description:
Measure:Disease control rate (DCR) [assessed by IRRC and investigator]
Time Frame:up to 6 month from LPI
Safety Issue:
Description:
Measure:Objective response rate (ORR) [assessed by investigator]
Time Frame:up to 6 month from LPI
Safety Issue:
Description:
Measure:Complete response rate (CR rate) [assessed by IRRC and investigator]
Time Frame:up to 6 month from LPI
Safety Issue:
Description:
Measure:Partial response rate (PR rate) [assessed by IRRC and investigator]
Time Frame:up to 6 month from LPI
Safety Issue:
Description:
Measure:Partial response duration (PR duration) [assessed by IRRC and investigator]
Time Frame:up to 6 month from LPI
Safety Issue:
Description:
Measure:Progression-free survival (PFS)
Time Frame:up to 6 month from LPI
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:up to 6 month from LPI
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Eutilex

Trial Keywords

  • Cytotoxic T cell
  • Lymphoma
  • Immuno-oncology
  • ENKTL
  • EBViNT

Last Updated