NCT06027879

Anti-viral T-cell Therapy by Gamma Capture

Anti-viral T-cell Therapy by Gamma Capture for High-risk Patients With Acquired or Inherited Immune Defects

• Status: Enrolling By Invitation
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Sponsor: Paul Szabolcs · Academic / Other
• Sex: All
• Age: 1 Month – 65 Years
• Healthy volunteers: Not accepted

Summary

The primary purpose of this phase I/II study is to evaluate whether partially matched, ≥1/6 Human Leukocyte Antigens (HLA) -matched, viral specific T cells have efficacy against adenovirus, Cytomegalovirus (CMV), and Epstein Barr Virus (EBV) in subjects who have previously received any type of allogeneic Hematopoietic Cell transplant (HCT) or solid organ transplant (SOT) or have compromised immunity. Reconstitution of anti-viral immunity by donor-derived cytotoxic T lymphocytes has shown promise in preventing and treating infections with adenovirus, CMV, and EBV. However, the weeks taken to prepare patient-specific products, and cost associated with products that may not be used limits their value. This trial will evaluate viral specific T cells generated by gamma capture technology. Eligible patients will include HCT and/or SOT recipients, and/or patients with compromised immunity who have adenovirus, CMV, or EBV infection or refractory viremia that is persistent despite standard therapy. Infusion of the cellular product will be assessed for safety and efficacy.

Detailed description

Enrollment for existing UPMC patients. Ideally, subjects will receive up to ≤1 x 105 (100,000) viable CD3 cells/kg however actual cell dose of infusion will be based upon available cells and subject's clinical picture. Historically, subjects have received all available cells after the gamma capture procedure. Two-weeks post initial cellular infusion, subject may be eligible to receive additional cellular infusions. If so, either the same or an alternative donor may be considered however, a subject will not receive more than 3 infusions from one donor or exceed 6 infusions in total from all donors. Infusions will be a minimum of 14-days apart. Subjects will not receive additional infusions if they exhibit Graft Versus Host Disease (GvHD) or Cytokine Release Syndrome (CRS) Grade II or higher, according to CTCAE v5. If a subject is to receive a second infusion, eligibility and baseline data collection will not be repeated for the recipient or original donor, unless necessary per institutional guidelines. Should an alternative donor be selected for an infusion, eligibility of the new donor will need confirmed. Pregnant donors may be considered if medically suitable. Two weeks post-initial cellular infusion, the following criteria will be assessed to determine if additional infusions are necessary: * Complete response: Return to normal range as defined by specific assay used and clinical signs and symptoms. These subjects are not eligible to receive an additional cellular infusion. * Partial response: Decrease in viral load of at least 50% from baseline or significant improvement of clinical signs. The clinical response is further defined as meeting one or more of the following criteria and no worsening in any of the others: 1. Absence of fever, if fever is present at baseline 2. No need for pressors, if on pressors at baseline 3. No need for oxygen and/or mechanical ventilation, if needed at baseline 4. Decrease in stool output, if is diarrhea present at baseline These subjects may receive additional cellular infusions as clinically indicated: * Stable disease: Changes insufficient to qualify as partial response or progression. These subjects are eligible to receive additional cellular infusions. * Progression: Increase in viral load of at least 50% from baseline or dissemination to other sites of disease. These subjects are eligible to receive additional cellular infusions. Subjects are followed for six months post initial viral-specific T cell infusion. If a subject receives additional infusions, GVHD and adverse events only will be followed for a minimum of three months from last infusion, even if extending beyond the six-month follow-up from the first infusion. Data may be abstracted from subjects' medical charts for an additional 1 year after most recent viral-specific T cell infusion.

Conditions

• Adenovirus
• Cytomegalovirus Infections
• Epstein-Barr Virus Infections

Interventions

Type	Name	Description
BIOLOGICAL	Specific T- Lymphocytes	Peripheral blood mononuclear cells will be collected from the donor and loaded onto Miltenyi Biotec CliniMACS Prodigy® or CliniMACS® Plus where they will be stimulated in vitro with Adenovirus viral-specific antigen(s). The cells are then immunomagnetically labeled with interferon gamma via the cytokine capture system, captured and infused.

Timeline

• Start date: 2024-01-08
• Primary completion: 2028-06-01
• Completion: 2029-06-01
• First posted: 2023-09-07
• Last updated: 2025-06-25

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study