Clinical Trials /

Tabelecleucel for Allogeneic Hematopoietic Cell Transplant Subjects With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab

NCT03392142

Description:

This is a multicenter, open label, single-arm, phase 3 study to assess the efficacy and safety of tabelecleucel for the treatment of Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) in the setting of allogeneic hematopoietic cell transplant (HCT) after failure of rituximab.

Related Conditions:
  • Post-Transplant Lymphoproliferative Disorder
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Tabelecleucel for Allogeneic Hematopoietic Cell Transplant Subjects With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab
  • Official Title: Multicenter, Open-Label, Phase 3 Study of Tabelecleucel for Allogeneic Hematopoietic Cell Transplant Subjects With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease After Failure of Rituximab

Clinical Trial IDs

  • ORG STUDY ID: ATA129-EBV-301
  • NCT ID: NCT03392142

Conditions

  • Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD)
  • Stem Cell Transplant Complications
  • Lymphoproliferative Disorders

Interventions

DrugSynonymsArms
tabelecleuceltab-cel®, ATA129, EBV-CTLtabelecleucel

Purpose

This is a multicenter, open label, single-arm, phase 3 study to assess the efficacy and safety of tabelecleucel for the treatment of Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) in the setting of allogeneic hematopoietic cell transplant (HCT) after failure of rituximab.

Detailed Description

      This is a multicenter, open label, single-arm, phase 3 study to assess the efficacy and
      safety of tabelecleucel for the treatment of EBV+ PTLD in the setting of allogeneic HCT after
      failure of rituximab.

      Tabelecleucel will be selected for the subject from the bank of available tabelecleucel cell
      products based on matching >= 2 human leukocyte antigen (HLA) alleles, at least one of which
      is a restricting HLA allele, shared between the tabelecleucel donor and the subject's EBV+
      PTLD. Sites will provide high resolution subject and subject's graft donor HLA typing results
      and other information as required by the protocol.

      Tabelecleucel will be administered in cycles lasting 5 weeks (35 days). During each cycle,
      subjects will receive intravenous (IV) tabelecleucel at a dose of 2×10^6 cells/kg on Days 1,
      8, and 15, followed by observation through Day 35.
    

Trial Arms

NameTypeDescriptionInterventions
tabelecleucelExperimentalTabelecleucel will be administered in cycles lasting 5 weeks (35 days). During each cycle, subjects will receive intravenous (IV) tabelecleucel at a dose of 2 x 10^6 cells/kg on Days 1, 8 and 15, followed by observation through Day 35. Treatment will continue until maximal response, unacceptable toxicity, initiation of non-protocol therapy, or failure of multiple tabelecleucel cell products.
  • tabelecleucel

Eligibility Criteria

        Inclusion Criteria:

          1. Prior allogeneic hematopoietic cell transplant

          2. A diagnosis of locally-assessed, biopsy-proven EBV+ PTLD with a pathology sample
             available for central review

          3. Availability of appropriate partially HLA-matched and restricted tabelecleucel cell
             product

          4. Measurable, 18F-deoxyglucose (FDG)-avid (Deauville score >= 3) systemic disease (using
             Lugano Classification response criteria) by positron emission tomography
             (PET)-diagnostic computed tomography (CT). Baseline scans must be of acceptable
             quality to the central radiology laboratory prior to Cycle 1 Day 1.

          5. Failure of rituximab for first-line treatment of PTLD. Note: Subjects with CD20
             negative disease are eligible to enroll without prior anti-CD20 therapy after failure
             of first-line treatment (reduction of immunosuppression is not considered first-line
             therapy) and discussion with the sponsor's medical monitor.

          6. Males and females of any age

          7. Eastern Cooperative Oncology Group (ECOG) performance status <= 3 for subjects aged >
             16 years; Lansky score >= 20 for subjects from birth to 16 years

          8. Underlying primary disease, for which the subject underwent transplant, is in
             morphologic remission

          9. Adequate organ function

               1. Absolute neutrophil count >= 500/µL, with or without cytokine support

               2. Platelet count >= 50,000/µL, with or without transfusion support; platelet count
                  < 50,000/µL but >= 20,000/µL, with or without transfusion support, is permissible
                  if the subject has not had Grade >= 2 bleeding in the prior 6 months (where
                  grading of the bleeding is determined per the National Cancer Institute's Common
                  Terminology Criteria for Adverse Events [CTCAE], version 5.0)

               3. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total
                  bilirubin (TBILI) each < 3 x the upper limit of normal (ULN); however, ALT, AST,
                  and TBILI each <= 5 x ULN is acceptable if the elevation is considered by the
                  investigator to be due to PTLD involvement of the liver

               4. Creatinine < 3 x ULN

         10. Subject or subject's representative is willing and able to provide written informed
             consent

        Exclusion Criteria:

          1. Daily steroids of > 0.5 mg/kg prednisone or glucocorticoid equivalent, methotrexate,
             or extracorporeal photopheresis

          2. History of central nervous system (CNS) PTLD

          3. Grade >= 2 graft-versus-host disease (GvHD) per the Center for International Blood and
             Marrow Transplant Research (CIBMTR) consensus grading system at enrollment

          4. Ongoing or recent use of a checkpoint inhibitor (eg, nivolumab, pembrolizumab,
             ipilimumab) within three drug half-lives from the most recent dose to Cycle 1 Day 1

          5. Active adenovirus viremia

          6. Need for vasopressor or ventilatory support

          7. Antithymocyte globulin or similar anti-T cell antibody therapy <= 4 weeks prior to
             Cycle 1 Day 1

          8. Treatment with Epstein-Barr virus cytotoxic T lymphocytes, chimeric antigen receptor
             (CAR)-T cells directed against B cells, or unselected donor lymphocyte infusion (DLI)
             within 8 weeks of Cycle 1 Day 1

          9. Pregnancy

         10. Female of childbearing potential or male with a female partner of childbearing
             potential unwilling to use a highly effective method of contraception

         11. Inability to comply with study-related procedures
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall survival (OS)
Time Frame:5 years
Safety Issue:
Description:
Measure:Duration of response (DOR)
Time Frame:2 years
Safety Issue:
Description:
Measure:PTLD progression-free survival (PFS) following best response
Time Frame:2 years
Safety Issue:
Description:
Measure:Rate of durable response
Time Frame:2 years
Safety Issue:
Description:
Measure:Time to progression
Time Frame:2 years
Safety Issue:
Description:
Measure:Patient reported outcome: EQ-5D
Time Frame:2 years
Safety Issue:
Description:
Measure:Patient reported outcome: Functional Assessment of Cancer Therapy Lymphoma (FACT-Lym)
Time Frame:2 years
Safety Issue:
Description:
Measure:Incidence of related and unrelated adverse events (AE), including AEs of special interest
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Atara Biotherapeutics

Trial Keywords

  • Epstein-Barr Virus (EBV)-associated Lymphoproliferative Disease (LPD)
  • Hematopoietic Cell Transplantation (HCT)
  • Hematopoietic Stem Cell Transplantation (HSCT)
  • Allogeneic Hematopoietic Cell Transplant
  • Bone Marrow Transplant Complications
  • Cancer After Transplant
  • Cytotoxic T lymphocyte (CTL)
  • Epstein-Barr Virus-specific Cytotoxic T Lymphocytes (EBV-CTL)
  • Allogeneic, Off-The-Shelf T-cell Immunotherapy
  • Post-transplant Lymphoma
  • Epstein-Barr Virus (EBV)

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