Clinical trial NCT02532452: Third Party Viral Specific T-cells (VSTs)
Official title: Third Party Viral Specific T-cells (VSTs) for Treatment of Viral Infections in Immunocompromised Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Viral Infection
Viral Reactivation
Infection in an Immunocompromised Host
Keywords: Epstein-Barr Virus (EBV)
Adenovirus (ADV)
Cytomegalovirus (CMV)
T-Cells
Donor
BK virus (BKV)
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
First posted: 2015-08-25
Enrollment: 750
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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 requiring treatment with chemotherapy
* 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

Primary outcomes:
measure: Successful production of viral specific T-cells
timeFrame: Within 30 days post culture initiation
measure: Percentage of patients who do not have infusional toxicity
timeFrame: Through 30 minutes post infusion
measure: Incidence of GVHD associated with VST infusion
timeFrame: Through 30 days after infusion
Secondary outcomes:
measure: Presence of viral-specific T-cells
timeFrame: At 30 days after infusion
measure: Viral burden
timeFrame: At 30 days after infusion
Other outcomes:
Locations:
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center - James Cancer Hospital
state: Ohio
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Michael Grimley, MD, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.