Third Party Viral Specific T-cells (VSTs)

Sponsor

Children's Hospital Medical Center, Cincinnati (Other)

Overall Status

Recruiting

CT.gov ID

NCT02532452

Collaborator

(none)

450

Enrollment

Location

Arm

101.9

Anticipated Duration (Months)

4.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Viral Infection Viral Reactivation Infection in an Immunocompromised Host	Biological: Viral Specific VST Infusion	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

450 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 2, 2015

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Mar 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Viral Specific VST Infusion 3rd party VST infusion	Biological: Viral Specific VST Infusion 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.

Arm

Intervention/Treatment

Experimental: Viral Specific VST Infusion

3rd party VST infusion

Biological: Viral Specific VST Infusion

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.

Outcome Measures

Primary Outcome Measures

Successful production of viral specific T-cells [Within 30 days post culture initiation]
Of the patients who had a VST culture initiated, successful production of VST cells is defined as meeting the protocol-defined release criteria.
Percentage of patients who do not have infusional toxicity [Through 30 minutes post infusion]
Patients will be monitored for infusional toxicity
Incidence of GVHD associated with VST infusion [Through 30 days after infusion]
Patients will be monitored for the development of VST associated GVHD

Secondary Outcome Measures

Presence of viral-specific T-cells [At 30 days after infusion]
Presence of viral-specific T-cells in the participant's blood will be assessed by Elispot assay
Viral burden [At 30 days after infusion]
The viral burden will be assessed using the protocol-defined efficacy assessment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Days and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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