Viral Specific T-Lymphocytes to Treat Adenovirus, CMV and EBV

NCT04364178 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: STUDY19040088
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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 or 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 DNA viruses. 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 or CMV 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

Keywords

Cytokine Capture System; Adenovirus; Cytomegalovirus; Hematopoietic Cell Transplant; Solid Organ Transplant; Immunocompromised; Inborn Error of Immunity

Outcome Measures

Primary Outcomes (2)

• Number of Patients With Grade III-IV Acute Graft Versus Host Disease

  Cumulative 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 (last infusion occurred up to 38 days post day 0)

• Number of Patients Who Experienced Grade 4/5 Adverse Events After Infusion

  Cumulative number of patients with CTCAE Grade 4/5 Adverse events which occurred after infusion

  Day 0 through 90 days after last cellular infusion (last infusion occurred up to 38 days post day 0)

Secondary Outcomes (6)

• Number of Patients Who Reached 6 Month Survival

  First cellular infusion to 6 months post first cellular infusion (last infusion occurred up to 38 days post day 0)

• Number of Patients Who Achieved One Year Survival

  1 year after first infusion

• Patients Who Achieved Viral Response (Complete Response) to Treatment

  1, 3, and 6 months after first infusion

• Number of Days to Patient Complete Response to Viral Specific Infusion

  Baseline through 6 months after last infusion

• Number of Days Post-VST Infusion Upon Which Viral Specific Antimicrobial Treatment Was Discontinued.

  Day 0 through 6 months after last 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 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: Adenovirus Specific T- Lymphocytes; Biological: Cytomegalovirus Specific T-Lymphocytes; Biological: EBV 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

EBV 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 (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.
• Clinical status, at time of consent, amendable to tapering of steroids 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.
• Diagnosis of Adenovirus or CMV 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 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.
• Active severe chronic GVHD.
• Received donor lymphocyte infusion, with the exception of a fraction of an umbilical cord blood, within 21 days of 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.
• 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, 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.
• years of age or older
• Able to understand and consent/assent to the procedure
• Required hemoglobin of 11g/dL or greater
• Partial (2/6 or more) HLA match to the recipient
• Donor is pregnant
• Donor is HIV positive
• Donor is positive for hepatitis B and/or hepatitis C

Sponsors & Collaborators

• Jessie L. Alexander, MD: lead

Study Sites (1)

UPMC (University of Pittsburgh Medical Center)

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

Results Point of Contact

• Title: Jessie Alexander, MD
• Organization: Stanford University

jlalex@stanford.edu

650-725-9250

Study Officials

• Jessie Alexander, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: April 23, 2020
• First Posted: April 27, 2020
• Study Start: August 12, 2020
• Primary Completion: February 9, 2023
• Study Completion: November 11, 2023
• Last Updated: May 27, 2026
• Results First Posted: May 27, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)