VST Infusion for Post-Transplant Viral Infections

(VSTs Trial)

Recruiting at 1 trial location

Overseen By Jamie Wilhelm, BS

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Children's Hospital Medical Center, Cincinnati

Must not be taking: ATG, Alemtuzumab

Disqualifiers: Acute GVHD, Uncontrolled infection, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: Up to 15 weeks

750 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how viral specific T-cells (VSTs) can combat viral infections after a donor bone marrow transplant. Such infections are common and pose significant risks to transplant recipients due to their weakened immune systems. The study evaluates whether VST infusions offer a simpler and safer alternative to standard antiviral treatments, which often have challenging side effects and are difficult to manage. Individuals who have undergone a stem cell transplant and meet specific health criteria may be suitable for this trial, particularly if they struggle with viral infections. As a Phase 1, Phase 2 trial, the study aims to understand the treatment's function in people and assess its effectiveness in an initial, smaller group, providing participants an opportunity to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that your clinical status must allow tapering of steroids to a certain level, which might mean adjustments to steroid use.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that viral specific T-cells (VSTs), a type of immune cell, could help treat viral infections after stem cell transplants. Studies have found that VSTs are generally safe and effective. They have been used successfully in both children and adults, with many patients experiencing no major safety issues.

One study demonstrated that VSTs helped control severe viral infections without causing serious side effects. This finding suggests they might be a safer option than traditional antiviral medicines, which can sometimes harm the kidneys or reduce blood cell counts. Overall, the evidence supports VSTs as a well-tolerated choice for patients facing these challenging viral infections. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Viral Specific T Cell (VST) Infusion because it offers a targeted approach to combating viral infections that occur after transplants. Unlike standard antiviral drugs, which can have broad effects and sometimes harmful side effects, VST Infusion uses immune cells specifically trained to recognize and fight viral infections without harming the body’s own cells. This precision in targeting viral threats reduces the risk of complications and can be especially beneficial for patients with weakened immune systems post-transplant. Additionally, VST Infusion has the potential to provide rapid and effective relief from viral reactivations, setting it apart from traditional treatments that may take longer to show results.

What evidence suggests that VST Infusion might be an effective treatment for post-transplant viral infections?

Research shows that virus-specific T cells (VSTs), a type of immune cell, could help treat viral infections following a donor stem cell transplant. This trial will evaluate the effectiveness of Viral Specific VST Infusion in managing such infections. Studies have found that VSTs can effectively control viral infections like cytomegalovirus, Epstein-Barr virus, and adenovirus in transplant patients. In cases where patients had active viral infections, about 80% went into remission, meaning the virus could no longer be detected. VSTs specifically target and destroy virus-infected cells, offering a possible alternative to standard antiviral medications, which may not work for everyone and can have difficult side effects. Overall, VSTs have proven both safe and effective in managing viral infections after a transplant. ^{1 2 3 5 6}

Who Is on the Research Team?

Michael Grimley, MD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Are You a Good Fit for This Trial?

This trial is for people who've had or will have a stem cell transplant from another person and are struggling with viral infections post-transplant. They must have stable white blood cell counts, be able to reduce steroid use, and be at least 21 days past their stem cell infusion. It's not for those recently treated with certain immune suppressants, experiencing severe graft-versus-host disease, uncontrolled bacterial/fungal infections, or cancer relapse.

Inclusion Criteria

It has been at least 21 days since my stem cell infusion.

Recipient must have achieved engraftment with ANC ≥ 500

I can reduce my steroid use to a low dose.

Exclusion Criteria

My cancer has returned and is not under control.

I received ATG or alemtuzumab treatment within the last 2 weeks.

I do not have any untreated bacterial or fungal infections.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive donor-derived viral specific T-cells (VSTs) to treat viral infections post-transplant. Up to 5 infusions may be given, with 21 days between each treatment, or 14 days if no viral response is observed.

Up to 15 weeks

Up to 5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after VST infusion, with physical exams and blood tests weekly until 30 days after the last infusion, and monthly monitoring for 1 year if possible.

12 months

Weekly visits for 1 month, then monthly visits for 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Viral specific VST Infusion

Trial Overview The study tests the effectiveness of infusing donor-derived T-cells that specifically target viruses in patients after allogeneic stem cell transplants. These special cells aim to combat common but potentially deadly viral infections that can occur when someone's immune system is weakened by a transplant.

How Is the Trial Designed?

Group I: Viral Specific VST Infusion Experimental Treatment 1 Intervention

Viral reactivation or infection. VST Reinfusion required.

Viral specific VST Infusion is already approved in United States, European Union for the following indications:

Approved in United States as Viral Specific T-cells for:

• Cytomegalovirus (CMV) infections
• Epstein-Barr virus (EBV) infections
• Adenovirus (ADV) infections
• BK virus (BKV) infections
• JC virus infections

Approved in European Union as Viral Specific T-cells for:

• Cytomegalovirus (CMV) infections
• Epstein-Barr virus (EBV) infections
• Adenovirus (ADV) infections
• BK virus (BKV) infections

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

Hoxworth Blood Center

Collaborator

Trials

7

Recruited

1,600+

Published Research Related to This Trial

A single session of high-intensity interval training (HIT) significantly increased the frequency of virus-specific T cells (VSTs) in donors, showing up to a fivefold higher response compared to continuous exercise.

Moderately fit donors had better responses in VST frequency after exercise, suggesting that HIT can enhance the effectiveness of T-cell donations, particularly for less common viral infections like CMV, EBV, and AdV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-intensity interval training in allogeneic adoptive T-cell immunotherapy - a big HIT? Heinemann, NC., Tischer-Zimmermann, S., Wittke, TC., et al.[2021]

Adoptive transfer of donor-derived virus-specific T cells (VSTs) has shown effectiveness in restoring immunity against viral infections after hematopoietic stem cell transplantation (HSCT), with success rates of 70% to 90% in recipients.

Recent studies have also demonstrated that using closely matched third-party VSTs can provide protection, achieving response rates of 60% to 70%, which is crucial for patients with virus-naïve donors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T cells for viral infections after allogeneic hematopoietic stem cell transplant. Bollard, CM., Heslop, HE.[2021]

In a study involving 30 hematopoietic stem cell transplant patients, early administration of third-party virus-specific T-cells (VSTs) alongside antiviral therapy resulted in a remarkable 100% viral response rate and a 94% complete response rate for cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections.

The treatment was found to be safe, with low rates of acute and chronic graft-versus-host disease (13% and 23%, respectively) and no serious infusion-related adverse events, while achieving excellent overall survival rates of 88% one year post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Third-party CMV- and EBV-specific T-cells for first viral reactivation after allogeneic stem cell transplant. Jiang, W., Clancy, LE., Avdic, S., et al.[2022]

A third-party virus-specific T cell (VST) bank was successfully established using discarded white cells from blood donors, showing significant cytotoxicity against multiple viruses like Adenovirus and Cytomegalovirus, which are often difficult to treat.

The study demonstrated that a carefully selected combination of just 6 VST lines could provide coverage for 99% of potential recipients in a multi-ethnic Asian population, indicating a cost-effective approach to enhance treatment options for opportunistic viral infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A cost-effective strategy for selection of third-party donors for a virus-specific T-cell bank for an Asian patient population. Linn, YC., Sundar Raj, K., Teo, B., et al.[2023]

A bank of 32 virus-specific T cell lines was successfully used to treat 50 patients with severe viral infections after stem cell transplants, resulting in a 74% overall response rate within 6 weeks, demonstrating the efficacy of this approach.

The treatment was safe, with no immediate infusion-related adverse events and only 2 cases of de novo graft-versus-host disease, indicating that using banked T cell lines can be a viable option for rapid antiviral therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation. Leen, AM., Bollard, CM., Mendizabal, AM., et al.[2022]

In a study of 30 allogeneic stem cell transplant patients with persistent viral infections, infusions of third-party virus-specific T cells (VSTs) were found to be safe and well tolerated, with a 93% overall response rate after 12 months.

The treatment led to durable virological control in most patients, with significant increases in CMV-specific T-cell immunity and CD8+ effector T cells, suggesting that third-party VSTs can effectively enhance the immune response against viral infections post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term control of recurrent or refractory viral infections after allogeneic HSCT with third-party virus-specific T cells. Withers, B., Blyth, E., Clancy, LE., et al.[2019]

In a study involving 28 patients and 32 virus-specific T cell (VST) treatments over 3 years, the average yield of viable VSTs was 1.83 million cells, with a mean purity of 62.9%, indicating a robust method for generating these cells for antiviral therapy.

The research found that the frequency of VSTs in the donor's blood, particularly for cytomegalovirus (CMV), strongly predicts the quantity of VSTs in the final product, emphasizing the importance of careful donor selection in optimizing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of the best-suited donor for generating virus-specific T cells. Tasnády, S., Karászi, É., Szederjesi, A., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36736781/

Third-Party and Patient-Specific Donor-Derived Virus ... Both donor-derived (DD) and third-party (TP) virus-specific T cells (VSTs) have shown efficacy and safety in viral management following HSCT in children and ...

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

Third-Party and Patient-Specific Donor-Derived Virus ... Both donor-derived (DD) and third-party (TP) virus-specific T cells (VSTs) have shown efficacy and safety in viral management following HSCT in children and ...

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

Outcomes following posttransplant virus-specific T-cell therapy ... Here, we report the outcomes of patients with SCD at a single-center who received VSTs after transplant to prevent or treat viral infections.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10196792/

Outcomes following posttransplant virus-specific T-cell ... Virus-specific T cells are safe in patients with SCD following hematopoietic stem cell transplant. In patients with active viremia, 80% achieved remission ...

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

Virus-Specific T Cells for the Treatment of Systemic Infections ... Virus-specific T cells for adenovirus infection after stem cell transplantation are highly effective and class II HLA restricted . Blood Adv.

6. amjtransplant.org amjtransplant.org/article/S1600-6135(24)00347-2/fulltext

Virus-specific T cell therapy to treat refractory viral ... Virus-specific T cell therapies aim to restore host-specific immunity to opportunistic viruses that is lacking due to ongoing immunosuppressive therapy.