Viral Specific T-Lymphocytes to Treat Infection With Adenovirus, Cytomegalovirus or Epstein-Barr Virus in Patients With Compromised Immunity

NCT06909110 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 73319
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 3

Brief Summary

The primary purpose of this phase I/II study is to evaluate whether partially matched, ≥2/6 HLA-matched, viral specific T cells have efficacy against adenovirus, CMV, and EBV, in subjects who have previously received any type of allogeneic 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. In this trial, we 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

Keywords

Cytokine Capture System; Adenovirus; Cytomegalovirus; Epstein-Barr Virus; Hematopoietic Cell Transplant; Solid Organ Transplant

Outcome Measures

Primary Outcomes (2)

• Grade III-IV Acute Graft versus host disease

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

  Day 0 through 90 days after last cellular infusion

• CTCAE Grade 4/5 Adverse Events

  The incidence of patients who develop CTCAE Grade 4/5 Adverse events related to infusion

  Day 0 through 30 days from last cellular infusion

Secondary Outcomes (9)

• Number of patients achieving 6-month survival (dichotomous)

  First cellular infusion to 6 months post first cellular infusion

• Viral load by Polymerase Chain Reaction (PCR)

  Baseline and 14 days, 1 month, 3 months, and 6 months after cellular infusion

• Viral load from Respiratory Viral Panel (RVP)

  Baseline and 14 days, 1 month, 3 months, and 6 months after cellular infusion

• Viral load from Bronchoalveolar lavage (BAL)

  Baseline and 14 days, 1 month, 3 months, and 6 months after cellular infusion

• Viral load from Urine

  Baseline and 14 days, 1 month, 3 months, and 6 months after cellular infusion

Study Arms (1)

Viral Specific T-Lymphocytes

EXPERIMENTAL

Peripheral blood mononuclear cells will be collected from the donor and loaded onto our Miltenyi Biotec 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: Adenovirus Specific T- Lymphocytes; Biological: Cytomegalovirus Specific T-Lymphocytes; Biological: Epstein-Barr Virus Specific T-Lymphocytes

Interventions

Adenovirus Specific T- Lymphocytes BIOLOGICAL

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 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

Cytomegalovirus Specific T-Lymphocytes BIOLOGICAL

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 Cytomegalovirus 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

Epstein-Barr Virus Specific T-Lymphocytes BIOLOGICAL

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 Epstein-Barr 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 patients ≥ 7 years of age who are developmentally able, assent or affirmation will be obtained, if feasible.
• Male or female, 1 month through 65 years old, inclusive, at the time of informed consent.
• Prior allogeneic hematopoietic stem cell transplant, AND/OR prior solid organ transplant (liver, kidney, lung and/or heart, intestinal, pancreatic, and/or multivisceral), AND/OR diagnosis of primary immunodeficiency AND/OR current/recent administration of immunosuppressive therapy for cancer or autoimmune disease.
• If receiving steroids, must be able to taper dose to less than 1 mg/kg/day prednisone (or equivalent) prior to cellular infusion.
• Negative pregnancy test for females ≥10 years old or who have reached menarche, unless surgically sterilized or post-menopausal.
• Diagnosis of Adenovirus, CMV, or EBV infection, persistent despite standard therapy.
• A. Adenovirus Infection or Disease (at minimum, one of the below sub-criteria must be met):
• 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)
• Refractory adenoviremia: defined as DNAemia ≥1000 copies/mL or \<1 log decrease after at least 2 weeks of appropriate antiviral therapy (i.e. cidofovir, brincidofovir, or other available pharmacological agents)
• Intolerance of or contraindication to antiviral medications.
• B. CMV Infection or Disease (at minimum, one of the below sub-criteria must be met):
• 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)
• Refractory CMV viremia: defined as the continued presence of DNAemia, with ≥1,000 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)
• Intolerance of or contraindication to antiviral medications.
• C. EBV Infection or Disease (at minimum, one of the below sub-criteria must be met):

You may not qualify if:

• Received ATG or Alemtuzumab within 21 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.
• Active severe chronic GVHD.
• Received donor lymphocyte infusion, with the exception of a fraction of an umbilical cord blood, within 21 days of planned viral-specific T cell infusion. Subjects receiving a fraction of an umbilical cord blood within 21 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).
• Anticipated initiation of new lymphotoxic therapy within 4 weeks of viral-specific T cell infusion.
• Patients who are pregnant or lactating.
• Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, or concomitant medications, 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.
• Age ≥ 12\*
• Able to understand and sign the consent/assent to the procedure
• Partial (2/6 or more) HLA match to the recipient
• A pediatric donor could be selected as a donor only if a suitable adult donor is not available (as attested by the research team) or is ineligible according to FACT requirements. For pediatric donors:
• Related to the recipient
• Apheresis does not need a blood prime before the procedure
• Adequate peripheral venous access

Sponsors & Collaborators

• Jessie L. Alexander: lead

Study Sites (3)

Jessie Alexander

Palo Alto, California, 94304, United States

COMPLETED

Lucile Packard Children's Hospital

Palo Alto, California, 94304, United States

RECRUITING

Lucile Packard Children's Hospital

Palo Alto, California, 94305, United States

RECRUITING

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

• Jessie Alexander, MD

  Stanford University

  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: Clinical Associate Professor of Pediatrics

Study Record Dates

• First Submitted: March 27, 2025
• First Posted: April 3, 2025
• Study Start: April 30, 2025
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): January 1, 2032
• Last Updated: August 14, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)