Clinical Trials /

Tabelecleucel for Solid Organ Transplant Subjects With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab or Rituximab and Chemotherapy

NCT03394365

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 solid organ transplant (SOT) after failure of rituximab or rituximab plus chemotherapy.

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

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: ATA129-EBV-302
  • NCT ID: NCT03394365

Conditions

  • Epstein-Barr Virus-Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD)
  • Solid Organ 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 solid organ transplant (SOT) after failure of rituximab or rituximab plus chemotherapy.

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 SOT after failure of
      rituximab or rituximab plus chemotherapy.

      Tabelecleucel cell products will be selected for the subject from a 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.

      Subjects will be enrolled into one of two cohorts based on therapy prior to enrollment:
      Cohort A, for those who have failed rituximab alone; and Cohort B, for those who have failed
      rituximab and have also received chemotherapy for the treatment of PTLD. Study procedures and
      product administration will be the same for each cohort.

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

Eligibility Criteria

        Inclusion Criteria:

          1. Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of
             these

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

          3. Availability of appropriate HLA partially-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). For subjects with treated central nervous
             system (CNS) disease, a head CT and/or brain/spinal magnetic resonance imaging (MRI)
             as clinically appropriate will be required to follow CNS disease response per Lugano
             Classification response criteria.

          5. Treatment failure of rituximab monotherapy (Cohort A) or rituximab plus any concurrent
             or sequentially administered chemotherapy regimen (Cohort B) for 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. Adequate organ function

               1. Absolute neutrophil count >= 1000/μL, with or without cytokine support

               2. Platelet count >= 50,000/μL, with or without transfusion or cytokine support

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

               4. Creatinine < 3×ULN

          9. 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. Untreated CNS PTLD or CNS PTLD for which the subject is actively receiving treatment
             at enrollment

          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 agent (eg ipilimumab, pembrolizumab,
             nivolumab) within three drug half-lives from the most recent dose to Cycle 1 Day 1

          5. Need for vasopressor or ventilatory support

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

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

          8. Pregnancy

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

         10. 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:Rate of durable response
Time Frame:2 years
Safety Issue:
Description:
Measure:PTLD progression-free survival (PFS) following best response
Time Frame:2 years
Safety Issue:
Description:
Measure:Time to progression
Time Frame:2 years
Safety Issue:
Description:
Measure:Rates of allograft loss or rejection episodes
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)
  • Epstein-Barr Virus (EBV)
  • Cytotoxic T lymphocyte (CTL)
  • Cancer After Transplant
  • Kidney transplant
  • Renal transplant
  • Liver transplant
  • Heart transplant
  • Lung transplant
  • Intestinal transplant
  • Pancreas transplant
  • Allogeneic, Off-The-Shelf T-cell Immunotherapy
  • Post-transplant Lymphoma
  • Solid Organ Transplant (SOT)

Last Updated