Antiviral Cellular Therapy for Enhancing T-cell Reconstitution Before or After Hematopoietic Stem Cell Transplantation
The purpose of this study is to evaluate whether virus-specific T cell lines (VSTs) are safe and can effectively control three viruses (EBV, CMV, and adenovirus) in patients who have had a stem cell transplant and also in patients that have a primary immunodeficiency disorder with no prior stem cell transplant.
Inclusion Criteria
- Patients with simultaneous infections with CMV, EBV and/or Adenovirus infections are eligible if one or more infection(s) is persistent or relapsed despite standard therapy as defined above. Patients with multiple infections with one or more reactivation and one or more controlled infection are eligible to enroll.
- Clinical status at enrollment that allows tapering of steroids to equal or less than 0.5 mg/kg/day prednisone (or equivalent) prior to infusion of the VST doses.
- Negative pregnancy test in female patients if applicable (childbearing potential who have received a reduced intensity conditioning regimen).
- Written informed consent and/or signed assent line from patient, parent or guardian.
Exclusion Criteria
- Patients receiving ATG, Campath, Basiliximab or other immunosuppressive monoclonal antibodies targeting T-cells within 28 days of screening for enrollment.
- Patients who have received donor lymphocyte infusion (DLI) or other experimental cellular therapies within 28 days.
- Current therapy with ruxolitinib or other JAK inhibitors within the previous 3 days.
- Patients with other uncontrolled infections, defined as bacterial or fungal infections with clinical signs of worsening despite standard therapy. For bacterial infections, patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment. For fungal infections, patients must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to enrollment.
- Progressing infection is defined as hemodynamic instability, worsening physical signs, or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
- Patients with active and uncontrolled relapse of malignancy (if applicable).
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03475212.
Locations matching your search criteria
United States
California
Los Angeles
Ohio
Cleveland
The primary purpose of the study is to evaluate whether most closely HLA-matched
multivirus-specific T cell lines obtained from a bank of allogeneic virus-specific T cell
lines (VSTs) have antiviral activity against three viruses: EBV, CMV and adenovirus.
Reconstitution of anti-viral immunity by donor-derived VSTs has shown promise in
preventing and treating infections associated with CMV, EBV and adenovirus
post-transplant. However, the time required to prepare patient-specific products and lack
of virus-specific memory T cells in cord blood and seronegative donors, limits their
value. An alternative is to use banked partially HLA-matched allogeneic VSTs. A prior
phase II study at Baylor College of Medicine using trivirus-specific VSTs generated using
monocytes and EBV-transformed B cells gene-modified with a clinical grade adenoviral
vector expressing CMV-pp65 to activate and expand specific T cells showed the
feasibility, safety and activity of this approach for the treatment of refractory CMV,
EBV and Adenovirus infections. More recent protocols utilizing synthetic viral peptide
pools allow ex vivo expansion of T-cells targeting multiple viral antigens in 10-12 days
without use of viral transduction.
The study will evaluate whether partially-HLA matched allogeneic multivirus-specific
VSTs, activated using overlapping peptide libraries spanning immunogenic antigens from
CMV, adenovirus and EBV, will be safe and produce anti-viral effects in immunodeficient
recipients infected with one of more of the targeted viruses that are persistent despite
conventional anti-viral therapy.
This study will evaluate safety and efficacy of partially-matched VST therapy in A)
patients who have persistent viral infections in the post-HSCT period, and B) patients
with primary immunodeficiency conditions who have persistent viral infections and have
not undergone HSCT.
The study agent will be assessed for safety and antiviral activity.
Trial PhasePhase I/II
Trial Typetreatment
Lead OrganizationPediatric Transplantation & Cellular Therapy Consortium
- Primary IDPBMTC SUP1701
- Secondary IDsNCI-2020-06312
- ClinicalTrials.gov IDNCT03475212