Clinical Trials /

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

NCT03394365

Description:

The purpose of this study is to determine the clinical benefit and characterize the safety profile of tabelecleucel for the treatment of Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) in the setting of (1) solid organ transplant (SOT) after failure of rituximab and rituximab plus chemotherapy or (2) 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 Solid Organ or Allogeneic Hematopoietic Cell Transplant Participants 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 or Allogeneic Hematopoietic Cell 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
  • Allogeneic Hematopoietic Cell Transplant
  • Stem Cell Transplant Complications

Interventions

DrugSynonymsArms
tabelecleuceltab-cel®, ATA129, EBV-CTLHCT cohort

Purpose

The purpose of this study is to determine the clinical benefit and characterize the safety profile of tabelecleucel for the treatment of Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) in the setting of (1) solid organ transplant (SOT) after failure of rituximab and rituximab plus chemotherapy or (2) allogeneic hematopoietic cell transplant (HCT) after failure of rituximab.

Detailed Description

      This is a multicenter, open-label, 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
      and rituximab plus chemotherapy (SOT cohort) or HCT after failure of rituximab (HCT cohort).

      Enrollment will be preceded by confirmation of availability of partially human leukocyte
      antigen (HLA) matched and restricted tabelecleucel for the participant.

      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, participants
      will receive intravenous tabelecleucel at a dose of 2×10^6 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 tabelecleucel with
      up to 2 different HLA restrictions (SOT cohort) or up to 4 different HLA restrictions (HCT
      cohort).

      This protocol has been amended to include the HCT cohort from clinical study ATA129-EBV-301
      (NCT03392142).
    

Trial Arms

NameTypeDescriptionInterventions
SOT cohort -Subgroup AExperimentalParticipants who have failed rituximab will receive IV tabelecleucel.
  • tabelecleucel
SOT cohort -Subgroup BExperimentalParticipants who have failed both rituximab and chemotherapy will receive IV tabelecleucel.
  • tabelecleucel
HCT cohortExperimentalParticipants who have failed rituximab will receive IV tabelecleucel.
  • tabelecleucel

Eligibility Criteria

        Inclusion Criteria:

          1. Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of
             these (SOT cohort); or prior allogeneic HCT (HCT cohort)

          2. A diagnosis of locally-assessed, biopsy-proven EBV+ PTLD

          3. Availability of appropriate partially HLA-matched and restricted tabelecleucel has
             been confirmed by the sponsor

          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), except when contraindicated or mandated by
             local practice, then magnetic resonance imaging (MRI) may be used.For subjects with
             treated central nervous system (CNS) disease, a head CT and/or brain/spinal MRI as
             clinically appropriate will be required to follow CNS disease response per Lugano
             Classification response criteria.

          5. Treatment failure of rituximab monotherapy (SOT cohort, subgroup A or HCT cohort) or
             rituximab plus chemotherapy (SOT cohort, subgroup B) for treatment of PTLD.

          6. Eastern Cooperative Oncology Group performance status ≤ 3 for subjects aged > 16
             years; Lansky score ≥ 20 for subjects from birth to 16 years

          7. For HCT cohort only: If allogeneic HCT was performed as treatment for an acute
             lymphoid or myeloid malignancy, the underlying primary disease for which the subject
             underwent transplant must be in morphologic remission

          8. Adequate organ function

               1. Absolute neutrophil count ≥ 1000/μL, (SOT cohort) or ≥ 500/μL (HCT cohort), with
                  or without cytokine support

               2. Platelet count ≥ 50,000/μL, with or without transfusion or cytokine support. For
                  HCT cohort, 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 4 weeks (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 < 5 × the upper limit of normal (ULN); however, ALT, AST,
                  and TBILI each ≤ 10 × ULN is acceptable if the elevation is considered by the
                  investigator to be due to EBV and/or PTLD involvement of the liver as long as
                  there is no known evidence of significant liver dysfunction (eg, elevated
                  prothrombin time due to liver dysfunction, signs/symptoms of liver dysfunction
                  such as asterixis, or similar).

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

        Exclusion Criteria:

          1. Burkitt lymphoma, classical Hodgkin lymphoma, or any T cell lymphoma

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

          3. Untreated CNS PTLD or CNS PTLD for which the subject is actively receiving
             CNS-directed chemotherapy (systemic or intrathecal) or radiotherapy at enrollment.
             NOTE:Subjects with previously treated CNS PTLD may enroll if CNS-directed therapy is
             complete.

          4. Suspected or confirmed grade ≥ 2 graft-versus-host disease (GvHD) per the Center for
             International Blood and Marrow Transplant Research (CIBMTR) consensus grading system
             at enrollment

          5. Ongoing or recent use of a checkpoint inhibitor agent (eg, ipilimumab, pembrolizumab,
             nivolumab) within 3 drug half-lives from the most recent dose to enrollment

          6. For HCT cohort: active adenovirus viremia

          7. Need for vasopressor or ventilatory support

          8. Antithymocyte globulin or similar anti-T cell antibody therapy ≤ 4 weeks prior to
             enrollment

          9. Treatment with Epstein-Barr virus cytotoxic T lymphocytes or chimeric antigen receptor
             (CAR) T cells directed against B cells within 8 weeks of enrollment (SOT or HCT
             cohorts), or unselected donor lymphocyte infusion within 8 weeks of enrollment (HCT
             cohort only)

         10. Female who is breastfeeding or pregnant or 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) in the SOT or HCT cohort
Time Frame:2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Duration of response (DOR) in SOT and HCT cohorts separately
Time Frame:2 years
Safety Issue:
Description:
Measure:ORR and DOR in SOT and HCT cohorts combined
Time Frame:2 years
Safety Issue:
Description:
Measure:Rates of complete response (CR) and partial response (PR)
Time Frame:2 years
Safety Issue:
Description:
Measure:Time to response
Time Frame:2 years
Safety Issue:
Description:
Measure:Time to best response
Time Frame:2 years
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:2 years
Safety Issue:
Description:
Measure:Rates of allograft loss or rejection episodes (SOT cohort)
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
  • Post-transplant Lymphoma
  • Solid Organ Transplant (SOT)
  • Bone Marrow Transplant Complications
  • Epstein-Barr Virus-specific Cytotoxic T Lymphocytes (EBV-CTL)
  • Hematopoietic Cell Transplant (HCT)
  • Hematopoietic Stem Cell Transplantation (HSCT)
  • Allogeneic Hematopoietic Cell Transplant
  • Allogeneic, Off-The-Shelf T-cell Immunotherapy

Last Updated

December 19, 2019