Third Party Viral Specific T-cells (VSTs)

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Third Party Viral Specific T-cells (VSTs) for Treatment of Viral Infections in Immunocompromised Patients

Conditions
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Viral Infection, Viral Reactivation, Infection in an Immunocompromised Host

Intervention / Treatment
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* Biological: Viral Specific VST Infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Immunocompromised patient with evidence of viral infection or reactivation Age >1 day Recipients who have had a stem cell transplant must be at least 21 days after stem cell infusion Clinical status must allow tapering of steroids to < 0.5mg/kg prednisone or other steroid equivalent Must be able to receive CTL infusion in Cincinnati Informed consent obtained by PI or sub-investigator either in person or by phone Exclusion Criteria: Active acute GVHD grades II-IV Uncontrolled bacterial or fungal infection Uncontrolled relapse of malignancy Infusion of ATG or alemtuzumab within 2 weeks of VST infusion

Ages Eligible for Study
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Minimum Age: 2 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Viral Specific VST Infusion<br>3rd party VST infusion | Biological: Viral Specific VST Infusion<br>* 3rd party VSTs will be infused into immunocompromised patients who have evidence of viral infection or reactivation defined as any of the following: Blood adenovirus PCR ≥ 1,000 Blood CMV PCR ≥ 500 Blood EBV PCR ≥ 9,000 Plasma BKV PCR >1,000 Plasma JC Virus PCR > 1,000 Evidence of invasive adenovirus infection or disease, defined as the presence of adenoviral positivity by PCR or culture in one or more sites. Evidence of invasive CMV infection, eg pneumonitis, retinitis, colitis Evidence of EBV-associated lymphoproliferation (EBV-LPD) defined as proven EBV-LPD by biopsy or probable EBV-LPD defined as an elevated EBV DNA level in the blood associated with clinical symptoms (adenopathy or fever or masses on imaging) but without biopsy confirmation, or EBV-associated malignancies. Evidence of symptomatic BK virus infection, which may include symptomatic hemorrhagic cystitis, or BK nephropathy. Evidence of PML or other CNS infection due to JC virus.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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. | At 30 days after infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epstein-Barr Virus (EBV), Adenovirus (ADV), Cytomegalovirus (CMV), T-Cells, Donor, BK virus (BKV)