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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

Trial Status: Active

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.

Inclusion Criteria

  • Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of these (SOT cohort); or prior allogeneic HCT (HCT cohort)
  • A diagnosis of locally-assessed, biopsy-proven EBV+ PTLD
  • Availability of appropriate partially HLA-matched and restricted tabelecleucel has been confirmed by the sponsor
  • 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.
  • Treatment failure of rituximab monotherapy (SOT cohort, subgroup A or HCT cohort) or rituximab plus chemotherapy (SOT cohort, subgroup B) for treatment of PTLD.
  • Eastern Cooperative Oncology Group performance status ≤ 3 for subjects aged ≥ 16 years; Lansky score ≥ 20 for subjects < 16 years
  • 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
  • Adequate organ function
  • Absolute neutrophil count ≥ 1000/μL, (SOT cohort) or ≥ 500/μL (HCT cohort), with or without cytokine support
  • 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)
  • Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin each < 5 × the upper limit of normal; however, ALT, AST, and total bilirubin each ≤ 10 × upper limit of normal 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
  • Subject or subject's representative is willing and able to provide written informed consent

Exclusion Criteria

  • Burkitt lymphoma, classical Hodgkin lymphoma, or any T cell lymphoma
  • Daily steroids of > 0.5 mg/kg prednisone or glucocorticoid equivalent, ongoing methotrexate, or extracorporeal photopheresis
  • 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.
  • 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
  • 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
  • For HCT cohort: active adenovirus viremia
  • Need for vasopressor or ventilatory support
  • Antithymocyte globulin or similar anti-T cell antibody therapy ≤ 4 weeks prior to enrollment
  • Treatment with Epstein-Barr virus cytotoxic T lymphocytes or chimeric antigen receptor 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)
  • 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
  • Inability to comply with study-related procedures

California

Duarte
City of Hope Comprehensive Cancer Center
Status: ACTIVE
Sacramento
University of California Davis Comprehensive Cancer Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
San Diego
University of California San Diego
Status: CLOSED_TO_ACCRUAL

Florida

Miami
University of Miami Miller School of Medicine-Sylvester Cancer Center
Status: ACTIVE

Georgia

Atlanta
Children's Healthcare of Atlanta - Egleston
Status: IN_REVIEW
Emory University Hospital / Winship Cancer Institute
Status: ACTIVE

Illinois

Chicago
University of Chicago Comprehensive Cancer Center
Status: ACTIVE

Maryland

Baltimore
University of Maryland / Greenebaum Cancer Center
Status: ACTIVE
Contact: Janaiya Samuels
Phone: 410-328-8199

Massachusetts

Boston
Boston Children's Hospital
Status: ACTIVE
Brigham and Women's Hospital
Status: ACTIVE
Dana-Farber Cancer Institute
Status: ACTIVE

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: ACTIVE

New York

Bronx
Montefiore Medical Center-Weiler Hospital
Status: ACTIVE
Contact: Ioannis Mantzaris
Phone: 718-920-4826
New York
Memorial Sloan Kettering Cancer Center
Status: ACTIVE
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: ACTIVE

North Carolina

Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: ACTIVE
Durham
Duke University Medical Center
Status: ACTIVE

Ohio

Cleveland
Case Comprehensive Cancer Center
Status: ACTIVE
Columbus
Nationwide Children's Hospital
Status: COMPLETED
Contact: Anthony N. Audino
Ohio State University Comprehensive Cancer Center
Status: ACTIVE

Oregon

Portland
OHSU Knight Cancer Institute
Status: ACTIVE

Pennsylvania

Philadelphia
Children's Hospital of Philadelphia
Status: ACTIVE
University of Pennsylvania / Abramson Cancer Center
Status: ACTIVE
Pittsburgh
University of Pittsburgh Cancer Institute (UPCI)
Status: ACTIVE

South Carolina

Charleston
Medical University of South Carolina
Status: ACTIVE

Tennessee

Nashville
Vanderbilt University / Ingram Cancer Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL

Texas

Dallas
UT Southwestern / Simmons Cancer Center-Dallas
Status: ACTIVE
Contact: Marcella West Aguilar
Phone: 214-648-1479
Houston
M D Anderson Cancer Center
Status: ACTIVE

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

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

(NCT03392142).

NOTE, 29 April 2020: Enrollment is temporarily paused at study site/locations with status

"active, not recruiting" due to COVID-19 restrictions.

Trial Phase Phase III

Trial Type Treatment

Lead Organization
Atara Biotherapeutics

  • Primary ID ATA129-EBV-302
  • Secondary IDs NCI-2018-00043
  • Clinicaltrials.gov ID NCT03394365