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

Launched by ATARA BIOTHERAPEUTICS · Jan 4, 2018

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called tabelecleucel for patients who have developed a condition known as Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) after receiving an organ or stem cell transplant. This condition can occur when the immune system is weakened after transplantation, leading to the uncontrolled growth of certain cells. The trial aims to find out if tabelecleucel is effective and safe for patients who have already tried other treatments, like rituximab and chemotherapy, without success.

To participate in this trial, patients must have had a solid organ transplant (like a kidney or liver) or a stem cell transplant and must have a confirmed diagnosis of EBV+ PTLD. They should also have measurable disease and meet certain health criteria to ensure they can safely receive treatment. Participants will be closely monitored throughout the study to assess the treatment's effectiveness and any potential side effects. It’s important to note that some patients may not be eligible due to specific health conditions or recent treatments. If you or a loved one is considering this trial, it may provide a new option for managing this challenging condition.

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Eligibility criteria

• 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 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 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 subjects aged ≥ 16 years; Lansky score ≥ 20 for subjects \< 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 subject underwent transplant must be in morphologic remission
• • 9. Adequate organ function
• • 1. Absolute neutrophil count ≥ 1000/μL, (C-SOT) or ≥ 500/μL (C-HCT), with or without cytokine support
• • 2. Platelet count ≥ 50,000/μL, with or without transfusion or cytokine support. For C-HCT, 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 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
• • 10. 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 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