Infection in an Immunocompromised Host, Viral Infection, Viral Reactivation
Conditions
Keywords
Epstein-Barr Virus (EBV), Adenovirus (ADV), Cytomegalovirus (CMV), T-Cells, Donor, BK virus (BKV)
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.
Interventions
BIOLOGICALViral 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
Sponsors
Children's Hospital Medical Center, Cincinnati
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Days to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Contacts
CONTACTJamie Wilhelm
CONTACTMichael Grimley, MD
PRINCIPAL_INVESTIGATORMichael Grimley, MD, MD
Children's Hospital Medical Center, Cincinnati
Outcome results
None listed