Third Party Viral Specific T-cells (VSTs)

Viral Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02532452
• Other study ID #: 2015-4184
• Status: Recruiting
• Phase: Phase 2
• Start date: September 2, 2015
• Est. completion date: December 2027

Study information

• Verified date: January 2024
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: Jamie Wilhelm
• Phone: (513) 803-1102
• Email: Jamie.Wilhelm[@]cchmc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 750
• Est. completion date: December 2027
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Days and older

Eligibility

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
• Biopsy confirmed acute rejection of solid organ transplant OR empiric treatment of suspected but not confirmed acute rejection of solid organ transplant within the last 30 days

Related Conditions & MeSH terms

• Communicable Diseases
• Infection in an Immunocompromised Host
• Infections
• Viral Infection
• Viral Reactivation
• Virus Diseases

Intervention

Biological:
• Viral Specific VST Infusion
VSTs will be infused into immunocompromised patients with 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 invasive EBV disease/infection, 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

Locations

Country	Name	City	State
United States	Akron Children's Hospital	Akron	Ohio
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	The Ohio State University Wexner Medical Center - James Cancer Hospital	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Percentage of patients who do not have infusional toxicity	Patients will be monitored for infusional toxicity	Through 30 minutes post infusion
Primary	Incidence of GVHD associated with VST infusion	Patients will be monitored for the development of VST associated GVHD	Through 30 days after infusion
Secondary	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
Secondary	Viral burden	The viral burden will be assessed using the protocol-defined efficacy assessment.	At 30 days after infusion