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?

In this research study, the investigators want to learn more about the use of donor-derived viral specific T-cells (VSTs) to treat viral infections that occur after allogeneic stem cell transplant. A viral specific T cell is a T lymphocyte (a type of white blood cell) that kills cells that are infected (particularly with viruses). Allogeneic means the stem cells come from another person. These VSTs are cells specially designed to fight the virus infections that can happen after a bone marrow transplant. The investigators are asking people who have undergone or will undergo an allogeneic stem cell transplant to enroll in this research study, because viral infections are a common problem after allogeneic stem cell transplant and can cause significant complications including death. Stem cell transplant reduces a person's ability to fight infections. There is an increased risk of getting new viral infections or reactivation of viral infections that the patient has had in the past, such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus (ADV), BK virus (BKV), and JC virus. There are anti-viral medicines available to treat these infections, though not all patients will respond to the standard treatments. Moreover, treatment of viral infections is expensive and time consuming, with families often administering prolonged treatments with intravenous anti-viral medications, or patients requiring prolonged admissions to the hospital. The medicines can also have side effects like damage to the kidneys or reduction in the blood counts, so in this study the investigators are trying to find an easier way to treat these infections.

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 VST infusion safe for humans?

VST infusion appears to be generally safe for humans, with studies showing no serious infusion-related adverse events and only a few cases of mild complications like graft-versus-host disease. The treatment has been well tolerated in patients, with good viral control and clinical outcomes. ^{1 2 3 4 5}

How is the VST Infusion treatment different from other treatments for post-transplant viral infections?

VST Infusion is unique because it uses virus-specific T cells (VSTs) from donors to restore virus-specific immunity in patients after a transplant, especially when conventional treatments fail. This approach can use banked third-party VSTs, making it a rapid and feasible option for treating severe viral infections without needing to generate a separate line for each patient. ^{1 3 4 6 7}

What data supports the effectiveness of the VST Infusion treatment for post-transplant viral infections?

Research shows that using virus-specific T cells (VSTs) from donors can effectively restore immunity and control viral infections in 70% to 90% of patients after a stem cell transplant. Additionally, a study found that using banked third-party VSTs led to a 74% response rate in patients with severe viral infections, with significant decreases in viral DNA and improvement in symptoms. ^{1 3 4 6 7}

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

Recipient must have achieved engraftment with ANC ≥ 500

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

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 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]

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]

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]

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]

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]

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]

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]

Citations

1. United States 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. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

T cells for viral infections after allogeneic hematopoietic stem cell transplant. [2021]

3. England pubmed.ncbi.nlm.nih.gov

High-intensity interval training in allogeneic adoptive T-cell immunotherapy - a big HIT? [2021]

4. England pubmed.ncbi.nlm.nih.gov

Identification of the best-suited donor for generating virus-specific T cells. [2020]

5. England 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. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Third-party CMV- and EBV-specific T-cells for first viral reactivation after allogeneic stem cell transplant. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Long-term control of recurrent or refractory viral infections after allogeneic HSCT with third-party virus-specific T cells. [2019]