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The purpose of this study is to demonstrate that viral specific T-cells (a type of white blood cell) can be generated from an unrelated donor and given safely to patients with viral infections.
Viral reactivation and infection is a major cause of morbidity in immunocompromised patients (including HSCT recipients). In this study we will draw blood from unrelated (third party) donors and use the blood to generate viral specific T-cells (VSTs) with specificity for Epstein-Barr virus (EBV), cytomegalovirus (CMV), adenovirus (ADV), BK virus (BKV), and JC Virus. The VSTs will be infused into immunocompromised children with specific viral infections (EBV, CMV, ADV, BKV , or JC virus). Cells will be selected for infusion based on the recipient's HLA type and the viral specificity of the cells.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Viral Specific VST Infusion | Experimental | 3rd party VST infusion |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Viral Specific VST Infusion | Biological | VSTs will be infused into immunocompromised patients with evidence of viral infection or reactivation defined as any of the following:
|
| Measure | Description | Time Frame |
|---|---|---|
| Successful production of viral specific T-cells | Of the patients who had a VST culture initiated, successful production of VST cells is defined as meeting the protocol-defined release criteria. | Within 30 days post culture initiation |
| Percentage of patients who do not have infusional toxicity | Patients will be monitored for infusional toxicity | Through 30 minutes post infusion |
| Incidence of GVHD associated with VST infusion | Patients will be monitored for the development of VST associated GVHD | Through 30 days after infusion |
| Measure | Description | Time Frame |
|---|---|---|
| Presence of viral-specific T-cells | Presence of viral-specific T-cells in the participant's blood will be assessed by Elispot assay | At 30 days after infusion |
| Viral burden | The viral burden will be assessed using the protocol-defined efficacy assessment. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jamie Wilhelm | Contact | (513) 803-1102 | Jamie.Wilhelm@cchmc.org | |
| Michael Grimley, MD | Contact | Michael.Grimley@cchmc.org |
| Name | Affiliation | Role |
|---|---|---|
| Michael Grimley, MD, MD | Children's Hospital Medical Center, Cincinnati | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Akron Children's Hospital | Recruiting | Akron | Ohio | 44308 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40991376 | Derived | Rubinstein JD, Pham G, Sridharan A, Khoury R, Wang YM, Hudda Z, Wilhelm J, Lichtenstein DA, Heyenbruch D, Cancelas JA, Davies SM, Lutzko C, Grimley MS. Outcomes with third-party virus-specific T cells after the use of single-antigen cell lines to predict HLA restriction. Blood Adv. 2025 Dec 23;9(24):6305-6313. doi: 10.1182/bloodadvances.2025017097. | |
| 36736781 |
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| ID | Term |
|---|---|
| D014777 | Virus Diseases |
| D020031 | Epstein-Barr Virus Infections |
| D000257 | Adenoviridae Infections |
| ID | Term |
|---|---|
| D007239 | Infections |
| D006566 | Herpesviridae Infections |
| D004266 | DNA Virus Infections |
| D014412 | Tumor Virus Infections |
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|
| At 30 days after infusion |
| University of Cincinnati Medical Center | Completed | Cincinnati | Ohio | 45219 | United States |
| Cincinnati Children's Hospital Medical Center | Recruiting | Cincinnati | Ohio | 45229 | United States |
|
| The Ohio State University Wexner Medical Center - James Cancer Hospital | Recruiting | Columbus | Ohio | 43210 | United States |
|
| Galletta TJ, Lane A, Lutzko C, Leemhuis T, Cancelas JA, Khoury R, Wang YM, Hanley PJ, Keller MD, Bollard CM, Davies SM, Grimley MS, Rubinstein JD. Third-Party and Patient-Specific Donor-Derived Virus-Specific T Cells Demonstrate Similar Efficacy and Safety for Management of Viral Infections after Hematopoietic Stem Cell Transplantation in Children and Young Adults. Transplant Cell Ther. 2023 May;29(5):305-310. doi: 10.1016/j.jtct.2023.01.027. Epub 2023 Feb 3. |
| 34473237 | Derived | Rubinstein JD, Zhu X, Leemhuis T, Pham G, Ray L, Emberesh S, Jodele S, Thomas S, Cancelas JA, Bollard CM, Hanley PJ, Keller MD, Grimley O, Clark D, Clark T, Lindestam Arlehamn CS, Sette A, Davies SM, Nelson AS, Grimley MS, Lutzko C. Virus-specific T cells for adenovirus infection after stem cell transplantation are highly effective and class II HLA restricted. Blood Adv. 2021 Sep 14;5(17):3309-3321. doi: 10.1182/bloodadvances.2021004456. |
| 33216887 | Derived | Nelson AS, Heyenbruch D, Rubinstein JD, Sabulski A, Jodele S, Thomas S, Lutzko C, Zhu X, Leemhuis T, Cancelas JA, Keller M, Bollard CM, Hanley PJ, Davies SM, Grimley MS. Virus-specific T-cell therapy to treat BK polyomavirus infection in bone marrow and solid organ transplant recipients. Blood Adv. 2020 Nov 24;4(22):5745-5754. doi: 10.1182/bloodadvances.2020003073. |