A Dose-Escalation Study Evaluating Safety and Tolerability of Viral-Specific T Cells Against CMV in Adult Solid Organ Transplant Recipients
Condition: Cytomegalovirus Infections; Solid Organ Transplant
MeSH terms: Cytomegalovirus Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      This study measures the tolerability of viral-specific T cells against Cytomegalovirus (CMV)
      in adult solid organ transplant (SOT) recipients. Participants are expected to be on study
      for 52 +/- 3 weeks.
    

Detailed description: 
      Viral infections, or their reactivation in the immunocompromised host, remain serious
      complications that adversely affect outcomes of transplantation. These infections may be
      refractory to pharmacologic treatment and result in increased morbidity and mortality after
      transplantation. Furthermore, the available pharmacologic therapies can result in severe
      toxicities.

      Once an infection occurs, adequate immune reconstitution is decisive for recovery from viral
      disease after solid organ transplantation. The present trial will consist of the treatment of
      solid organ transplant recipients diagnosed with severe CMV infection when standard antiviral
      therapy is ineffective (disease progression on therapy, decline in viral load less than
      10-fold in 2 weeks, known drug resistance), or toxic (end-organ damage), with virus-specific
      T cells using the CliniMACS® Prodigy System. These are the patients with the greatest unmet
      need and greatest risk or morbidity and allograft loss due to CMV infection. CMV-specific T
      cells will be isolated from donor leukapheresis products using the CliniMACS® Prodigy. Prior
      studies on transfer of CMV-specific T cells have been shown to be safe and efficacious in the
      treatment of CMV infections.

      The primary objective of this Phase I trial is to evaluate the safety and tolerability of
      CMV-specific T-cell transfer in adult patients suffering from CMV infections following solid
      organ transplantation using a dose escalation design. The incubation with viral antigens
      (MACS GMP PepTivator) allows the enrichment of CMV-specific CD4+(Cluster of Differentiation
      4) and CD8+(Cluster of Differentiation 8) T cells. Increasing evidence of the safety and
      efficacy of CMV-specific T-cell is available. Furthermore, the safety and efficacy of the
      specific manufacturing approach using the fully automated protocol of the ClinMACS® Prodigy
      for the isolation of CMV-specific T cells against CMV has been described and demonstrated
      that these cells retain their biological properties.
    

Intervention name(s): CMV specific T-cells
Intervention type(s): Biological
Intervention description(s): Naturally occurring, allogeneic donor lymphocytes derived from a leukapheresis or a whole blood product, enriched for CMV-specific CD4+ and CD8+ T cells Suspension of CMV-specific T cells in 10 mL of 0.9% NaCl with 2% Human Serum Albumin(HSA) via IV bolus injection
Low Dose Tier - Viral-Specific T cell infusion 5 x10^3 cells/kg body weight(BW)
Mid Dose Tier - Viral-Specific T cell infusion 1.25 x10^4 cells/kg BW
High Dose Tier - Viral-Specific T cell infusion 2.5 x10^4 cells/kg BW Product will be administered fresh intravenously to recipient within four hours of collection.
Intervention model: Single Group Assignment
Intervention model description: 3+3 dose-escalation, open label, non-randomized, non-placebo controlled, single group assignment study
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: T-cell; immunotherapy