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A Phase 3 Study of Tabelecleucel for Participants With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease After Failure With Rituximab or Rituximab and Chemotherapy

PHASE3RECRUITING

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 (SOT-R) and rituximab plus chemotherapy (SOT-R+C) or (2) allogeneic hematopoietic cell transplant (HCT) after failure of rituximab.

Study details:

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-R and SOT-R+C (Cohort \[C\]-SOT) or HCT after failure of rituximab (C-HCT). SOT-R further included participants:. 1.

who did not receive chemotherapy and did not have a documented medical reason not to receive chemotherapy (SOT-Ro) or. 2. who were considered chemotherapy ineligible/inappropriate (SOT-R-Ci).

Combined population (SOT-R-Ci, SOT-R+C, and HCT) and (SOT-R-Ci and SOT-R+C) who received commercial product, or a product manufactured using a comparable process version (PV) were also used for analysis of outcomes. 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 (C-SOT) or up to 4 different HLA restrictions (C-HCT).

The study includes a total of 5 years of follow-up for disease and survival status.

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  1. Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of these (C-SOT); or prior allogeneic HCT (C-HCT).
  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 participants 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 or interchangeable commercially available biosimilar monotherapy (C-SOT-R or C-HCT) or rituximab plus any concurrent or sequentially administered chemotherapy regimen (C-SOT-R+C) for treatment of PTLD.
  6. Males and females of any age.
  7. Eastern Cooperative Oncology Group performance status ≤ 3 for participants aged ≥ 16 years; Lansky score ≥ 20 for participants < 16 years.
  8. For C-HCT only: If allogeneic HCT was performed as treatment for an acute lymphoid or myeloid malignancy, the underlying primary disease for which the participant underwent transplant must be in morphologic remission.
  9. Adequate organ function.
  10. Participant or participant'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 participant is actively receiving CNS-directed chemotherapy (systemic or intrathecal) or radiotherapy at enrollment. NOTE: Participants 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 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 C-HCT: 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 T cells directed against B cells within 8 weeks of enrollment (C-SOT or C-HCT), or unselected donor lymphocyte infusion within 8 weeks of enrollment (C-HCT 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.
  12. Any medical condition or organ system dysfunction that in the investigator's opinion, could compromise the participant's safety or ability to complete the study.

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

study type

Study type

TREATMENT

phase

Phase

    PHASE3

trial

Study ID

NCT03394365

Intervention or treatment

BIOLOGICAL: tabelecleucel

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

  • Condition: Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Solid Organ Transplant Complications and more

  • BIOLOGICAL: tabelecleucel

  • Westmead, New South Wales, Australia and more

  • Sponsor: Pierre Fabre Medicament

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Research sites nearby

Closest Location:

The Children's Hospital at Westmead (Pediatrics only)

Select from list below to view details:

  • The Children's Hospital at Westmead (Pediatrics only)

    Westmead, New South Wales, Australia

  • Westmead Hospital (Adults only)

    Westmead, New South Wales, Australia

  • The Prince Charles Hospital (Adults only)

    Chermside, Queensland, Australia

  • Royal Adelaide Hospital (Adults only)

    Adelaide, South Australia, Australia

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Who is running the clinical trial?

PFM

Pierre Fabre Medicament

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/ArmIntervention/Treatment
EXPERIMENTAL: Cohort SOT-R (C-SOT-R)
  • Participants with EBV+ PTLD following SOT that has failed rituximab will receive IV tabelecleucel.
Biological: tabelecleucel
    EXPERIMENTAL: Cohort SOT-R+C (C-SOT-R+C)
    • Participants with EBV+ PTLD following SOT that has failed both rituximab and chemotherapy will receive IV tabelecleucel.
    Biological: tabelecleucel
      EXPERIMENTAL: Cohort HCT (C-HCT)
      • Participants with EBV+ PTLD following HCT that has failed rituximab containing regimen will receive IV tabelecleucel.
      Biological: tabelecleucel

        What is the study measuring?

        Primary Outcome

        MeasureDescriptionTime Frame
        Objective Response Rate (ORR) in the Analysis Cohorts C-SOT, C-HCT, and Combined Population (C-SOT-R+C, C-SOT-R-Ci, and C-HCT) Who Received Commercial Product, or a Product Manufactured Using a Comparable PVNot Specified2 years

        Secondary Outcome

        MeasureDescriptionTime Frame
        Duration of Response (DOR) in the Analysis Cohorts C-SOT and C-HCT SeparatelyNot Specified2 years
        ORR in the Analysis Cohorts C-SOT and C-HCT CombinedNot Specified2 years
        ORR and DOR in Participants who Received Commercial Product or a Product Manufactured Using a Comparable PV in the Analysis Cohorts C-SOT-R-Ci and C-SOT-R+C Separately and Combined, and in the Analysis Cohort C-HCTNot Specified2 years
        DOR in the Analysis Cohort of the Combined Population (C-SOT-R+C, C-SOT-R-Ci, and C-HCT) who Received Commercial Product or a Product Manufactured Using a Comparable PVNot Specified2 years
        Rates of Complete Response (CR) and Partial Response (PR)Not Specified2 years
        Time to ResponseNot Specified2 years
        Time to Best ResponseNot Specified2 years
        Overall Survival (OS)Not Specified2 years
        Rates of Allograft Loss or Rejection Episodes (Analysis Cohort C-SOT)Not Specified2 years
        Are you running this trial?If you're a clinic or sponsor, you can claim this study.
        Claim this trial

        References

        Clinical Trials Gov: A Phase 3 Study of Tabelecleucel for Participants With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease After Failure With Rituximab or Rituximab and Chemotherapy

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