VST Therapy for Viral Infections

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Catherine Bollard

Must not be taking: ATG, Campath

Disqualifiers: Uncontrolled infections, GVHD grade 2, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 6-12 weeks

31 Participants Needed

Trial Summary

What is the purpose of this trial?

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 taken 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 our institution 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. However, the production process was lengthy, requiring 8-12 weeks, with exposure to biohazards (B95.8 EBV viral strain and adenovector), while antigenic competition between different viral components precluded increasing the spectrum of specificity beyond these three viruses. Investigator have overcome these limitations and in the current trial, they will evaluate whether rapidly generated, allogeneic most closely HLA-matched 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 allogeneic HSCT recipients infected with one of more of the targeted viruses that are persistent despite conventional anti-viral therapy. The study agent will be assessed for safety (stopping rules defined) and antiviral activity.

Research Team

Catherine Bollard, MD

Principal Investigator

Children's National Research Institute

Eligibility Criteria

This trial is for allogeneic hematopoietic stem cell transplant recipients with persistent viral infections (EBV, CMV, adenovirus) despite treatment. Participants must have stable vital signs and organ function, not be pregnant, and able to consent. Excluded are those with uncontrolled infections or malignancies, recent immunosuppressive therapies or donor lymphocyte infusions.

Inclusion Criteria

Available VSTs

I am receiving cell therapy for a persistent or relapsed infection.

Pulse oximetry of > 90% on room air

Exclusion Criteria

I haven't received T cell immunosuppressive drugs in the last 28 days.

I have a graft-versus-host disease of grade 2 or higher.

I received a donor lymphocyte infusion in the last 28 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single infusion of partially HLA-matched VSTs, with up to 4 additional doses possible for partial responders

6-12 weeks

1 initial visit for infusion, followed by up to 4 additional visits at 2-week intervals

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of antiviral immunity and adverse events

12 months

Regular monitoring visits

Treatment Details

Interventions

• VSTs

Trial Overview The study tests if HLA-matched virus-specific T cell lines (VSTs) from a bank can fight viruses in transplant patients who haven't responded to standard antiviral treatments. It checks the safety of these ready-made VSTs and their effectiveness against EBV, CMV, and adenovirus.

Participant Groups

Group I: VSTs against three viruses Experimental Treatment 1 Intervention

Patients will receive 2 x 107 partially HLA-matched VSTs/m2 as a single infusion. In the rare case where insufficient banked cell product is available, a lower number of cells may be infused after discussion with the principal investigator, patient and/or guardian and the treatment team. If participants have a partial response (as defined by a 50% fall in viral load) they are eligible to receive up to 4 additional doses from day 28 after the initial infusion and at 2 weekly intervals thereafter.

Who Is Running the Clinical Trial?

Catherine Bollard

Lead Sponsor

Trials

13

Recruited

290+