Novel Antigens Targeted by ex Vivo Expanded T-Lymphocytes for Prevention or Treatment of Viral Infections Following Hematopoietic Stem Cell Transplantation

Pro00008637

This Phase I dose-escalation trial is designed to evaluate the safety of rapidly generated multivirus-specific T-cell products with antiviral activity against CMV, EBV, adenovirus, HHV6, BK virus, JC virus, and human parainfluenza-3 (HPIV3), derived from eligible HSCT donors. In this trial, we will utilize a rapid generation protocol for broad spectrum multivirus-specific T cells for infusion to recipients of allogeneic hematopoietic stem cell transplant (HSCT), who are at risk of developing EBV, CMV, adenovirus, HHV6, BKV, JCV and/or HPIV3, or with PCR/culture confirmed active infection(s) of EBV, CMV, adenovirus, HHV6, BKV, JCV, and/or HPIV3 that has failed to resolve with at least 14 days of standard antiviral therapy (if available and tolerated). These cells will be derived from HSCT donors, and the study agent will be assessed at each dose for evidence of dose-limiting toxicities (DLT). This study will have two arms: Arm A will include patients who receive prophylactic treatment, and Arm B will include patients who receive VSTs for one or more active infections with targeted viruses. Determination of the study arm will be determined by the patient's clinical status. Study arms will each be analyzed for safety endpoints and secondary endpoints.

2017-02-15

2024-10-01

2024-11-01

Active (not recruiting)

Early phase I

32

Recipient Inclusion Criteria at the Time of Initial VST Infusion and Subsequent Infusions: 1. Prior myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant using either bone marrow or peripheral blood stem cells no earlier than 5 days prior to the date of VST infusion. VSTs administered as: 1. Prophylaxis for patients at risk of EBV, CMV, adenovirus, HHV6, BKV, JCV and/or HPIV3. 2. Treatment of reactivation or active infection(s) with EBV, CMV, adenovirus, HHV6, BKV, JCV, and/or HPIV3 that has failed to resolve with at least 14 days of standard antiviral therapy (if available and tolerated). Patients with multiple infections due to the targeted viruses are also eligible. 2. Clinical status at infusion allows for tapering of steroids to less than 0.5 mg/kg/day prednisone or equivalent. 3) Karnofsky/Lansky score of ≥ 50. 4) Bilirubin ≤ 2x, AST ≤5x, Serum creatinine ≤2x upper limit of normal, Hgb ≥8.0 g/dL (level can be achieved with transfusion). 5) Pulse oximetry of \> 90% on room air. 6) Available multivirus-specific cytotoxic T lymphocytes 7) Negative pregnancy test (if female of childbearing potential). 8) Patient or parent/guardian capable of providing informed consent. Recipient Exclusion Criteria at the Time of Initial VST Infusion and Subsequent Infusions 1. Patients with other uncontrolled infections. 2. Patients who received ATG, Campath, Basiliximab or other T cell immunosuppressive monoclonal antibodies within 28 days prior to VST infusion. 3. Received donor lymphocyte infusion or other cellular therapies (with the exception of allogeneic cells related to transplantation) within 28 days prior to VST infusion. 4. Evidence of acute GVHD grades II-IV. 5. Active and uncontrolled relapse of malignancy. 6. Patients with Grade ≥ 3 hyperbilirubinemia. 7. Patients who have received investigational (IND) product within 28 days prior VST infusion.

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2023-09-21