Anti-viral T-cell Therapy by Gamma Capture

NCT06027879 | Enrolling By Invitation Phase 1 DMC FDA Drug

• 1 other identifier: STUDY23030062
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Adenovirus; Cytomegalovirus Infections; Epstein-Barr Virus Infections

Outcome Measures

Primary Outcomes (19)

• Grade III-IV Acute GvHD

  The number of patients who develop Grade III-IV acute graft versus host disease (GVHD) attributed to the viral specific T cells.

  Day 0

• Grade III-IV Acute GvHD

  The number of patients who develop Grade III-IV acute graft versus host disease (GVHD) attributed to the viral specific T cells.

  1 month from first cellular infusion

• Grade III-IV Acute GvHD

  The number of patients who develop Grade III-IV acute graft versus host disease (GVHD) attributed to the viral specific T cells.

  3 month from first cellular infusion

• Grade III-IV Acute GvHD

  The number of patients who develop Grade III-IV acute graft versus host disease (GVHD) attributed to the viral specific T cells.

  6 month from first cellular infusion

• Clinical response to treatment of viral infection

  Rate of Elimination or reduction of oxygen dependence identified at baseline

  1 month from first cellular infusion

• Clinical response to treatment of viral infection

  Rate of Resolution of diarrhea attributable to the viral disease, less than 4 stools daily

  1 month from first cellular infusion

• Clinical response to treatment of viral infection

  Rate of Resolution of fever, attributable to viral disease

  1 month from first cellular infusion

• Clinical response to treatment of viral infection

  Rate of Resolution or improvement of radiographic findings attributable to viral disease

  1 month from first cellular infusion

• Clinical response to treatment of viral infection

  Rate of Resolution or improvement of lymphadenopathy attributable to EBV, and ophthalmic findings attributable to CMV retinitis

  1 month from first cellular infusion

• Clinical response to treatment of viral infection

  Rate of Elimination or reduction of oxygen dependence identified at baseline

  3 month from first cellular infusion

• Clinical response to treatment of viral infection

  Rate of Resolution of diarrhea attributable to the viral disease, less than 4 stools daily

  3 month from first cellular infusion

• Clinical response to treatment of viral infection

  Rate of Resolution of fever, attributable to viral disease

  3 month from first cellular infusion

• Clinical response to treatment of viral infection

  Rate of Resolution or improvement of radiographic findings attributable to viral disease

  3 month from first cellular infusion

• Clinical response to treatment of viral infection

  Rate of Resolution or improvement of lymphadenopathy attributable to EBV, and ophthalmic findings attributable to CMV retinitis

  3 month from first cellular infusion

• Clinical response to treatment of viral infection

  Rate of Elimination or reduction of oxygen dependence identified at baseline

  6 months from first cellular infusion

• Clinical response to treatment of viral infection

  Rate of Resolution of diarrhea attributable to the viral disease, less than 4 stools daily

  6 months from first cellular infusion

• Clinical response to treatment of viral infection

  Rate of Resolution of fever, attributable to viral disease

  6 months from first cellular infusion

• Clinical response to treatment of viral infection

  Rate of Resolution or improvement of radiographic findings attributable to viral disease

  6 months from first cellular infusion

• Clinical response to treatment of viral infection

  Rate of Resolution or improvement of lymphadenopathy attributable to EBV, and ophthalmic findings attributable to CMV retinitis

  6 months from first cellular infusion

Secondary Outcomes (9)

• 1-year overall survival from first cellular infusion (continuous)

  First cellular infusion to 1 year post first cellular infusion

• Incidence of Graft rejection

  3 months after last cellular infusion

• Incidence of Graft rejection

  6 months after last cellular infusion

• Incidence of Mechanical ventilation exceeding 48 hours

  3 months after last cellular infusion

• Incidence of Mechanical ventilation exceeding 48 hours

  6 months after last cellular infusion

Study Arms (1)

Viral Specific T-Lymphocytes

EXPERIMENTAL

Viral Specific T-Lymphocytes Peripheral blood mononuclear cells will be collected from the donor and loaded onto our Miltenyi Biotec CliniMACS Prodigy® or CliniMACS® Plus where they will be stimulated in vitro with viral-specific antigen(s). The cells are then immunomagnetically labeled with interferon gamma via the cytokine capture system. By this method, viral specific, gamma-secreting T cells, are captured in a closed, sterile system.

Biological: Specific T- Lymphocytes

Interventions

Specific T- Lymphocytes BIOLOGICAL

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.

Viral Specific T-Lymphocytes

Eligibility Criteria

• Age: 1 Month - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient, parent, or legal guardian must have given written informed consent, according to FDA guidelines. For pediatric subject who are developmentally able, assent or affirmation will be obtained, if feasible.
• Male or female, 1 month through 75 years old, inclusive, at the time of informed consent.
• Prior allogeneic hematopoietic stem cell transplant (bone marrow, peripheral blood stem cells, single or double cord blood), OR prior solid organ transplant (liver, kidney, lung and/or heart, intestinal, or multivisceral), OR diagnosis of primary immunodeficiency OR current/recent administration of immunosuppressive therapy for cancer or autoimmune disease.
• Negative pregnancy test for females ≥10 years old or who have reached menarche, unless surgically sterilized. All females of childbearing potential and lactation must agree to use an FDA approved method of birth control for the duration of their participation.
• Clinical status, at the time of consent, amendable to tapering of steroids to less than 1 mg/kg/day prednisone (or equivalent) prior to cellular infusion.
• Diagnosis of Adenovirus, CMV, or EBV infection, persistent despite standard therapy.
• A. Adenovirus Infection or Disease:
• Active adenovirus infection: (i.e. gastroenteritis, pneumonia, hemorrhagic cystitis, hepatitis, pancreatitis, meningitis) defined as the demonstration of adenovirus by biopsy specimen from affected site(s) (by culture or histology), or the detection of adenovirus by culture, PCR or direct fluorescent antibody stain in fluid in the presence of worsening or persistent clinical or imaging findings despite at least 14 days of appropriate antiviral therapy (i.e. cidofovir, brincidofovir, or other available pharmacological agents) OR
• Refractory adenoviremia: defined as DNAemia \>5000 copies/mL or \<1 log decrease after at least 2 weeks of appropriate antiviral therapy (i.e. cidofovir, brincidofovir, or other available pharmacological agents) OR
• Intolerance of or contraindication to antiviral medications.
• B.CMV Infection or Disease:
• Active CMV infection: (i.e. pneumonia, meningitis, retinitis, hepatitis, hemorrhagic cystitis, and/or gastroenteritis) defined as the demonstration of CMV by biopsy specimen from affected site(s) (by culture or histology) or the detection of CMV by culture, PCR or direct fluorescent antibody stain in fluid in the presence of worsening or persistent clinical or imaging findings despite at least 14 days of appropriate antiviral therapy (i.e. Foscarnet, ganciclovir, cidofovir, or other available pharmacological agents) OR
• Refractory CMV viremia: defined as the continued presence of DNAemia, with ≥2,000 IU/mL or \<1 log decrease after at least 14 days of appropriate antiviral therapy (i.e. Foscarnet, ganciclovir, cidofovir, or other available pharmacological agents) OR
• Intolerance of or contraindication to antiviral medications.
• C. EBV Infection or Disease:

You may not qualify if:

• Received Antithymocyte Globulin (ATG) or Alemtuzumab within 28 days of viral-specific T cell infusion and a lack of evidence of T cell survival, defined by \<10 CD3+ T cells/uL (in unique situations, plasmapheresis may be considered).
• Active acute GVHD grades II-IV.
• Received donor lymphocyte infusion, with the exception of a fraction of an umbilical cord blood, within 14 days of viral-specific T cell infusion. Subjects receiving a fraction of an umbilical cord blood within 14 days of the viral-specific T cell infusion will not be excluded.
• Active and uncontrolled relapse of malignancy (other than EBV+ post-transplant lymphoproliferative disorder or lymphoma).
• Received an investigational product in the preceding 2 weeks (prior to infusion) that may impact Viral Specific T-cells (VST) survival.
• Females of child bearing potential must not be lactating.
• Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks to participation in the study, may interfere with the participant's ability to comply with study requirements, or that may impact the quality or interpretation of the data obtained from the study.

Sponsors & Collaborators

• Paul Szabolcs: lead

Study Sites (1)

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

MeSH Terms

Conditions

Adenoviridae Infections; Cytomegalovirus Infections; Epstein-Barr Virus Infections

Condition Hierarchy (Ancestors)

DNA Virus Infections; Virus Diseases; Infections; Herpesviridae Infections; Tumor Virus Infections

Study Officials

• Paul Szabolcs, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief, Division of Blood and Marrow Transplantation and Cellular Therapies, Medical Director of the Stem Cell Laboratory

Study Record Dates

• First Submitted: July 5, 2023
• First Posted: September 7, 2023
• Study Start: January 8, 2024
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2029
• Last Updated: June 25, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)