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

Launched by JESSIE L. ALEXANDER · Mar 27, 2025

Keywords

ClinConnect Summary

This clinical trial is exploring a new treatment option for patients who have weakened immune systems and are infected with certain viruses, specifically adenovirus, cytomegalovirus (CMV), or Epstein-Barr virus (EBV). The researchers want to see if a special type of immune cell, called viral specific T cells, can help fight these infections in patients who have had bone marrow or organ transplants or those with other immune system issues. The goal is to determine if these T cells, which are made using a specific technology, can effectively help patients recover from these stubborn viral infections.

To be eligible for the trial, patients must be between 1 month and 65 years old, have had a recent organ or bone marrow transplant, or suffer from a primary immunodeficiency. They should also have a current infection with adenovirus, CMV, or EBV that hasn't improved with standard treatments. Before joining, patients and their guardians will need to provide written consent, and there are some health conditions that may not allow participation. If you participate, you will receive an infusion of the T cells, and the researchers will closely monitor your health to assess safety and effectiveness. This trial is not yet recruiting participants, but it offers hope for improved treatments for those dealing with serious viral infections.

Gender

ALL

Eligibility criteria

• • Patient Inclusion Criteria
• • 1. 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.
• • 2. Male or female, 1 month through 65 years old, inclusive, at the time of informed consent.
• • 3. 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.
• • 4. 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.
• • 5. Negative pregnancy test for females ≥10 years old or who have reached menarche, unless surgically sterilized.
• • 6. Diagnosis of Adenovirus, CMV, or EBV infection, persistent despite standard therapy.
• A. Adenovirus Infection or Disease:
• • 1. 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
• • 2. 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
• • 3. Intolerance of or contraindication to antiviral medications.
• B. CMV Infection or Disease:
• • 1. 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
• • 2. 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
• • 3. Intolerance of or contraindication to antiviral medications.
• C. EBV Infection or Disease:
• • 1. EBV DNAemia ≥1000 IU/mL, persistent despite 2 doses of rituximab
• • 2. Biopsy proven lymphoma or posttransplant lymphoproliferative disease with EBV genomes detected in tumor cells by immunocytochemistry (i.e. EBER positive) or in situ PCR, OR
• • 3. Clinical or imaging findings consistent with EBV lymphoma and associated elevated EBV viral load in peripheral blood in a patient where biopsy is deemed too high risk, OR
• • 4. Failure of antiviral therapy, as determined by one of the two bullets below after three weeks of anti-CD20 targeted therapy such as rituximab.
• • i. There was an increase or less than 50% response at sites of lymphoma disease or lymphoproliferation.
• • ii. There was a rise or a fall of less than 50% in EBV viral load in peripheral blood of PTLD patients.
• • e) Intolerance or contraindication to rituximab
• Patient Exclusion Criteria:
• • 1. 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).
• • 2. Active acute GVHD grades II-IV.
• • 3. Active severe chronic GVHD.
• • 4. 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.
• • 5. Active and uncontrolled relapse of malignancy (other than EBV+ post-transplant lymphoproliferative disorder or lymphoma).
• • 6. Anticipated initiation of new lymphotoxic therapy within 4 weeks of viral-specific T cell infusion.
• • 7. Patients who are pregnant or lactating.
• • 8. 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.
• • Donor Inclusion Criteria
• • 1. Able to understand and consent/assent to the procedure
• • 2. Adequate peripheral venous access or willingness to undergo central venous catheter placement
• • 3. For pediatric donors, apheresis does not need a blood prime before the procedure
• • 4. Partial (2/6 or more) HLA match to the recipient
• • 5. Signed informed consent
• • Donor Exclusion Criteria
• • 1. Donor is pregnant
• • 2. Donor is HIV positive
• • 3. Donor is positive for hepatitis B and/or hepatitis C
• • 4. Deemed to be a high-risk donor based on responses to donor risk questionnaire
• • 5. Deemed high risk due to preexisting medical condition or abnormal lab results