Clinical Trials /

Cellular Immunotherapy Treatment Antigen-Directed for EBV Lymphoma

NCT01948180

Description:

To investigate the efficacy of autologous EBV-specific T-cells for the treatment of patients with aggressive EBV positive extranodal NK/T-cell lymphoma

Related Conditions:
  • Mature T-Cell and NK-Cell Lymphoma/Leukemia
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Cellular Immunotherapy Treatment Antigen-Directed for EBV Lymphoma
  • Official Title: A Phase 2 Single Arm Study to Investigate the Efficacy of Autologous EBV-specific T-cells for the Treatment of Patients With Aggressive EBV Positive Extranodal NK/T-cell Lymphoma (ENKTCL)

Clinical Trial IDs

  • ORG STUDY ID: CM-2013-01
  • NCT ID: NCT01948180

Conditions

  • Lymphoma, Extranodal NK-T-Cell
  • EBV

Interventions

DrugSynonymsArms
baltaleucel-TCMD-003baltaleucel-T

Purpose

To investigate the efficacy of autologous EBV-specific T-cells for the treatment of patients with aggressive EBV positive extranodal NK/T-cell lymphoma

Trial Arms

NameTypeDescriptionInterventions
baltaleucel-TExperimentalTreatment consists of 2 infusions of 2x10E7 cells/m2 given on Days 1 and 15 intravenously via a peripheral or central line over a 1 to 10 minute period. Subjects who tolerate the study treatment well and who do not require treatment with an alternative chemotherapeutic agent will be eligible for up to 3 additional infusions of 2x10E7 cells/m2 administered at week 8, month 3 and month 6.
  • baltaleucel-T

Eligibility Criteria

        FOR SCREENING PHASE:

        Inclusion Criteria:

          1. Diagnosis of extranodal NK/T lymphoma, per WHO classification, 4th ed., which must
             include EBV tumor positivity, measured either by EBV encoded RNA (EBER) or LMP1
             immunostaining.

          2. a) Active Disease

        (1) Clinically suspected or documented relapse/progression, in first or second relapse
        following at least one cycle of an asparaginase-based chemotherapy regimen OR (2) Initial
        disease or first or second relapse and unable to tolerate one full cycle of
        asparaginase-based chemotherapy regimen OR b) High-risk disease (stage III/IV, KPI groups
        3-4 or IPI intermediate-high) prior to second CR regardless of previous chemotherapy.

        3. Male or female ≥ 18 years of age. 4. Weigh ≥ 35 kg. 5. ECOG performance score 0-2,
        inclusively. 6. Negative β-hCG test in women of childbearing potential. 7. Able to
        understand and comply with the requirements of the study and to provide written informed
        consent.

        Exclusion Criteria:

          1. CNS lymphoma.

          2. NK cell leukemia.

          3. Hemophagocytic lymphohistiocytosis.

          4. Positive for HIV, hepatitis B, hepatitis C, syphilis or human T Cell leukemia virus
             (HTLV).

          5. Use of systemic corticosteroids >0.5 mg/kg/day within 10 days prior to obtaining 200
             mL whole blood starting material.

          6. Patient is pregnant or lactating.

          7. Active second malignancy.

          8. Any prior allogeneic hematopoietic stem cell or solid organ transplant.

          9. Asparaginase refractory disease, defined by any one of the following:

               1. Progression at any time during initial asparaginase based chemotherapy and up to
                  3 months after end of initial asparaginase based chemotherapy, OR

               2. Failure to achieve at least PR with initial asparaginase based chemotherapy.

         10. Absolute lymphocyte count (ALC) <400/µL.

         11. Any previous autologous EBV specific T cell treatment.

         12. Systemic fungal, bacterial, viral or other infection that is not controlled.

         13. Third or greater relapse.

        FOR TREATMENT PHASE:

        Inclusion Criteria:

          1. Documented relapse or progression following at least one prior cycle of an
             asparaginase-containing chemotherapy regimen.

          2. Active disease based on any one of the following present at the baseline study visit
             or within two weeks prior to the baseline study visit:

               1. Imaging (may use local imaging)

               2. Clinical sign(s) including skin lesions consistent with lymphoma, organ
                  dysfunction or organomegaly not attributable to other causes; or other clinical
                  sign(s)

               3. Detectable blood or plasma ENV DNA (may use local laboratory)

          3. Completed most recent course of chemotherapy at least 2 weeks prior to first study
             drug dose.

          4. Recovery from acute hematological, hepatic and renal chemotherapy-related toxicities
             as defined by ≤ Grade 1 according to NCI CTCAE v4.0.

          5. Life expectancy ≥ 8 weeks.

        Exclusion Criteria:

          1. Use of any investigational agents within prior 4 weeks.

          2. Radiotherapy within prior 3 weeks.

          3. Major surgery within prior 2 weeks.

          4. Systemic corticosteroids within 24 hours prior to study drug administration.

          5. Evidence of hepatic dysfunction based on serum total bilirubin >3 times upper limit of
             normal (ULN), or ALT >5 times ULN or AST >5 times ULN.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate
Time Frame:1 year
Safety Issue:
Description:Defined as best observed response (complete response or partial response) per Lugano 2014 Disease Response Criteria.

Secondary Outcome Measures

Measure:Complete Response Rate
Time Frame:1 year
Safety Issue:
Description:
Measure:Response Duration
Time Frame:2 years
Safety Issue:
Description:
Measure:Time to Response
Time Frame:1 year
Safety Issue:
Description:
Measure:Progression Free Survival
Time Frame:2 years
Safety Issue:
Description:
Measure:Disease Free Survival
Time Frame:2 years
Safety Issue:
Description:
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:
Measure:Adverse Events
Time Frame:1 year
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:Cell Medica Ltd

Trial Keywords

  • NKTCL
  • T cell
  • CITADEL
  • Epstein-Barr Virus
  • Natural Killer

Last Updated

March 13, 2019