NCT03475212

Antiviral Cellular Therapy for Enhancing T-cell Reconstitution Before or After Hematopoietic Stem Cell Transplantation

Antiviral Cellular Therapy for Enhancing T-cell Reconstitution Before or After Hematopoietic Stem Cell Transplantation (ACES) PBMTC SUP1701

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 52 (actual)
• Sponsor: Pediatric Transplantation & Cellular Therapy Consortium · Academic / Other
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to evaluate whether virus-specific T cell lines (VSTs) are safe and can effectively control three viruses (EBV, CMV, and adenovirus) in patients who have had a stem cell transplant and also in patients that have a primary immunodeficiency disorder with no prior stem cell transplant.

Detailed description

The primary purpose of the study is to evaluate whether most closely HLA-matched multivirus-specific T cell lines obtained from a bank of allogeneic virus-specific T cell lines (VSTs) have antiviral activity against three viruses: EBV, CMV and adenovirus. Reconstitution of anti-viral immunity by donor-derived VSTs has shown promise in preventing and treating infections associated with CMV, EBV and adenovirus post-transplant. However, the time required to prepare patient-specific products and lack of virus-specific memory T cells in cord blood and seronegative donors, limits their value. An alternative is to use banked partially HLA-matched allogeneic VSTs. A prior phase II study at Baylor College of Medicine using trivirus-specific VSTs generated using monocytes and EBV-transformed B cells gene-modified with a clinical grade adenoviral vector expressing CMV-pp65 to activate and expand specific T cells showed the feasibility, safety and activity of this approach for the treatment of refractory CMV, EBV and Adenovirus infections. More recent protocols utilizing synthetic viral peptide pools allow ex vivo expansion of T-cells targeting multiple viral antigens in 10-12 days without use of viral transduction. The study will evaluate whether partially-HLA matched allogeneic multivirus-specific VSTs, activated using overlapping peptide libraries spanning immunogenic antigens from CMV, adenovirus and EBV, will be safe and produce anti-viral effects in immunodeficient recipients infected with one of more of the targeted viruses that are persistent despite conventional anti-viral therapy. This study will evaluate safety and efficacy of partially-matched VST therapy in A) patients who have persistent viral infections in the post-HSCT period, and B) patients with primary immunodeficiency conditions who have persistent viral infections and have not undergone HSCT. The study agent will be assessed for safety and antiviral activity.

Conditions

• Cytomegalovirus Infections
• Adenovirus Infection
• EBV Infection

Interventions

Type	Name	Description
BIOLOGICAL	Virus Specific T-cell (VST) infusion	Patients will receive partially HLA-matched VSTs as a single infusion. Patients who have a partial response (\>1 log decrease in viral load without clearance) or no response and do not have treatment-related dose-limiting toxicities are eligible to receive up to 3 additional doses from day 30 after the initial infusion and at 2 weekly intervals thereafter. The viral load of the virus (or viruses) that patients are initially treated for are monitored by viral PCR.

Timeline

• Start date: 2018-06-20
• Primary completion: 2025-06-30
• Completion: 2025-06-30
• First posted: 2018-03-23
• Last updated: 2025-05-11

Locations

30 sites across 1 country: United States

Regulatory

• FDA-regulated drug study