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.

Conditions

Eligibility

Eligible Ages
All ages
Eligible Genders
All
Accepts Healthy Volunteers
No

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
  9. Absolute neutrophil count ≥ 1000/μL, (SOT cohort) or ≥ 500/μL (HCT cohort), with or without cytokine support
  10. 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)
  11. 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).
  12. 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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
SOT cohort -Subgroup A
Participants who have failed rituximab will receive IV tabelecleucel.
  • Biological: tabelecleucel
    Tabelecleucel is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ malignancies and diseases.
    Other names:
    • tab-cel®
    • ATA129
    • EBV-CTL
Experimental
SOT cohort -Subgroup B
Participants who have failed both rituximab and chemotherapy will receive IV tabelecleucel.
  • Biological: tabelecleucel
    Tabelecleucel is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ malignancies and diseases.
    Other names:
    • tab-cel®
    • ATA129
    • EBV-CTL
Experimental
HCT cohort
Participants who have failed rituximab will receive IV tabelecleucel.
  • Biological: tabelecleucel
    Tabelecleucel is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ malignancies and diseases.
    Other names:
    • tab-cel®
    • ATA129
    • EBV-CTL

Recruiting Locations

Montefiore Medical Center (Adults only)
Bronx, New York 10467
Contact:
Ioannis Mantzaris, MD
718-910-4826
imantzar@montefiore.org

Montefiore Medical Center (Pediatrics only)
Bronx, New York 10467
Contact:
David Loeb, MD, PhD
718-741-2342
dloeb@montefiore.org

More Details

Status
Recruiting
Sponsor
Atara Biotherapeutics

Study Contact

Minoti Hiremath, MBBS, PhD
805-796-4080
clinicalstudies@atarabio.com

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).

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.