VST Therapy for Viral Infections

No longer recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called VSTs, which are special immune cells designed to combat three persistent viruses: EBV, CMV, and adenovirus. Researchers aim to determine if these rapidly produced VSTs can safely assist individuals who have undergone a stem cell transplant and continue to struggle with these viral infections despite standard treatments. Suitable candidates for this study are those who have had a stem cell transplant and are dealing with these specific viral infections that resist usual care. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it does mention that you should not have received certain immunosuppressive treatments like ATG or Campath in the last 28 days.

What prior data suggests that this VST therapy is safe for treating viral infections?

Research has shown that VST therapy is generally safe for people. One study examined various trials and found that side effects from VST therapy are usually mild and treatable, indicating the treatment is well-tolerated. Another study found that VSTs from both donors and third parties effectively and safely manage viral infections after a stem cell transplant. These findings suggest that VST therapy has a promising safety profile for individuals with viral infections. Overall, evidence indicates that VSTs are a safe option for treating viral infections, with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

VSTs (virus-specific T-cells) are unique because they harness the body's immune system to fight viral infections directly. Unlike standard antiviral medications that target the virus itself, VSTs are engineered immune cells that specifically recognize and attack infected cells. This personalized approach can adapt to combat multiple viruses simultaneously, offering a potentially more efficient and long-lasting solution compared to traditional drugs. Researchers are excited about VSTs because they could significantly reduce viral loads quickly and provide a new avenue for treating patients who don't respond well to existing therapies.

What evidence suggests that VSTs might be an effective treatment for viral infections?

Research has shown that special immune cells, called virus-specific T cells (VSTs), can help treat infections from viruses like CMV, EBV, and adenovirus, especially after transplants. In earlier studies, VSTs completely cleared the virus in about two-thirds of CMV cases, meaning the virus was no longer found in those patients. Even when the VSTs were not a perfect match, they still worked well, with 25 patients responding positively to the treatment. In this trial, participants will receive VSTs targeting three viruses, which could be a strong option for fighting these challenging viral infections. ^{1 3 6 7 8}

Who Is on the Research Team?

Catherine Bollard, MD

Principal Investigator

Children's National Research Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40991376/

Outcomes with Third Party Virus Specific T-cells After the ... Here we report on 25 patients who received TP VSTs for the treatment of 26 viral infections with at least one match at an HLA restricted site.

2. academic.oup.com academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaf302/8159933

Effectiveness and Safety of Autologous Virus-Specific T-Cell ... In this prospective study (N = 12), autologous virus-specific T cells (auto-VSTs) were successfully manufactured in 10 patients (83.3%).

3. sciencedirect.com sciencedirect.com/science/article/pii/S2666636723000647

Third-Party and Patient-Specific Donor-Derived Virus ... The primary study outcome was clinical response to VSTs, evaluated 4 weeks after VST administration, defined as decrease in viral load to under the inclusion ...

4. ashpublications.org ashpublications.org/bloodadvances/article/7/10/2105/493725/Outcomes-following-posttransplant-virus-specific-T

Outcomes following posttransplant virus-specific T-cell therapy ... Seven patients (53.8%) received VSTs prophylactically to prevent viral infection or reactivation after receiving transplant (Table 2). Two of ...

5. academic.oup.com academic.oup.com/jpids/article/13/Supplement_1/S49/7615748

Virus-Specific T Cells for the Treatment of Systemic Infections ... VSTs have proven highly effective for the treatment of CMV viremia with complete viral clearance observed in about two-thirds of cases. Similar ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6750917/

Adverse Effects of Virus-Specific T-Cell Therapy Studies reviewed indicate that the adverse effects associated with VST therapy are limited and generally treatable.

7. ashpublications.org ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2024013727/546897/Harnessing-Viral-Specific-T-Cells-Expanding

Harnessing Viral-Specific T Cells: Expanding Therapeutic ... This review explores the manufacturing, feasibility, safety, and efficacy of VSTs complemented by two case studies illustrating their real-world ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04331275

Viral Specific T-cells for Treatment of Viral Infections After ... VSTs are cells specially designed to fight viral infections that may happen after a solid organ transplant. These cells are created from a blood sample ...