Viral Specific T-cells for Post-Transplant Viral Infections

Overseen By Jamie Wilhelm, BS

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Hospital Medical Center, Cincinnati

Must not be taking: ATG, Alemtuzumab

Disqualifiers: Acute GVHD, Uncontrolled malignancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: 21-100 days

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to prevent and treat viral infections in individuals who have received a stem cell transplant from another person. It uses viral specific T-lymphocytes (VSTs), which are special cells designed to fight infections. The trial includes two groups: one receives VSTs shortly after their transplant to prevent infections, while the other receives them only if an infection develops. Suitable candidates have had a stem cell transplant and are experiencing frequent viral infections or complications from current treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but it does require that any steroids be reduced to less than 0.5mg/kg of prednisone or its equivalent. If you are taking ATG or alemtuzumab, you must not have had an infusion within 2 weeks before the VST infusion.

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

Research has shown that special immune cells called viral specific T-cells (VSTs) are being studied for their ability to treat viral infections after stem cell transplants. In earlier studies, patients received VSTs to help prevent and treat these infections. The results indicated that VSTs were generally safe, with no serious side effects directly linked to the treatment. Some mild side effects, like fever or chills, were reported but were manageable.

Although this treatment is still being tested, it resembles other T-cell therapies that have been safely used for different conditions. The current trial is at a stage where researchers are gathering more information on its safety and effectiveness. Initial safety results are encouraging, but further research is needed to confirm them. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for viral infections?

Unlike the standard antiviral medications used for post-transplant viral infections, Viral Specific T-cells (VSTs) offer a unique approach by using the body's own immune cells to target and fight off viral infections. Researchers are excited about VSTs because they can be tailored to recognize specific viruses, potentially offering a more precise and effective treatment. Additionally, VSTs can be administered either preventatively or as a treatment if an infection occurs, providing flexibility in managing potential viral threats post-transplant. This personalized and adaptable approach could lead to better outcomes and fewer side effects compared to traditional antiviral drugs.

What evidence suggests that Viral Specific T-cells might be an effective treatment for post-transplant viral infections?

Research has shown that special immune cells called viral specific T-cells (VSTs) can help manage viral infections after stem cell transplants. Some studies found that just one dose of these T-cells can clear up viral infections. For instance, in kidney transplant patients with adenovirus (ADV) infections, VSTs resolved the infection after a single treatment. VSTs have also proven safe and helpful for patients with sickle cell disease who have had stem cell transplants. In this trial, participants will receive VSTs either to prevent viral infections, administered 21-30 days after transplant, or to treat viral infections if they develop. Overall, early evidence supports using VSTs to both prevent and treat viral infections in transplant patients. ^{2 3 4 5 6}

Who Is on the Research Team?

Stella Davies, MBBS, PhD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Are You a Good Fit for This Trial?

This trial is for individuals who've had a stem cell transplant from another person at least 21 days ago, can reduce steroid use to low levels, and aren't critically ill. It's not for those with active moderate-to-severe graft-versus-host disease, uncontrolled cancer relapse, or recent treatment with certain immune-suppressing drugs.

Inclusion Criteria

Evidence of invasive adenovirus infection

Blood EBV PCR ≥ 9,000

I have a CMV infection affecting my lungs, eyes, colon, or liver.

Exclusion Criteria

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

My cancer has returned and is not under control.

I am experiencing moderate to severe symptoms of graft-versus-host disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

VSTs are administered to prevent or treat viral infections post-transplant

21-100 days

VSTs given through IV infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Viral Specific T-cells (VSTs)

Trial Overview The study tests whether giving viral specific T-cells (VSTs) on a schedule or as needed can prevent or treat viral infections after an allogeneic stem cell transplant. VSTs are designed to fight viruses that patients may be vulnerable to post-transplant.

How Is the Trial Designed?

Group I: VSTs to Treat Experimental Treatment 1 Intervention

VSTs will be given only if a viral infection develops.

Group II: VSTs to Prevent Experimental Treatment 1 Intervention

VSTs are given through an IV infusion 21-30 days after transplant to see if the VSTs will help prevent a viral infection.

Viral Specific T-cells (VSTs) is already approved in United States, European Union for the following indications:

Approved in United States as Posoleucel for:

• Adenovirus infections
• BK virus infections
• Cytomegalovirus infections
• Epstein-Barr virus infections
• Human herpes virus-6 infections
• JC virus infections

Approved in European Union as Posoleucel for:

• Adenovirus infections
• BK virus infections
• Cytomegalovirus infections
• Epstein-Barr virus infections
• Human herpes virus-6 infections
• JC virus 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

In a study involving 36 patients with primary immunodeficiencies (PIDs), virus-specific T lymphocytes (VSTs) demonstrated an 81% response rate in treating viral infections, indicating their efficacy in this vulnerable population.

The overall survival rate at 6 months post-VST therapy was 80%, suggesting that VSTs are not only effective but also safe, with manageable adverse effects such as graft-versus-host disease in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive immunotherapy for primary immunodeficiency disorders with virus-specific T lymphocytes. Naik, S., Nicholas, SK., Martinez, CA., et al.[2023]

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 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 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 virus-specific cytotoxic T lymphocytes (VSTs) has emerged as a promising immunotherapeutic approach to effectively combat viral infections after hematopoietic stem cell transplantation (HSCT), offering a way to restore antiviral immunity without causing graft-versus-host disease.

This review highlights the potential of VSTs to improve outcomes for patients suffering from life-threatening viral infections post-transplant and discusses strategies to expand their use beyond individual patient products and into other viral diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Virus-Specific T Cells: Broadening Applicability. Barrett, AJ., Prockop, S., Bollard, CM.[2021]

Virus-specific T-cell (VST) therapy offers a promising alternative to traditional antiviral agents, as it can effectively treat viral infections without causing drug resistance or significant toxicity, particularly in patients who are unresponsive to other treatments after hematopoietic cell transplantation (HCT).

Studies have shown that VST therapy is effective against various viruses, including herpes and polyomaviruses, and can be safely administered without causing severe graft-versus-host disease (GVHD), suggesting its potential for broader use in treating opportunistic infections in immunocompromised patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy for refractory viral infections]. Morio, T., Fujita, Y., Takahashi, S.[2019]

Posoleucel, a multivirus-specific T-cell therapy, was found to be safe and well tolerated in a phase II trial involving 58 allo-HCT recipients, with no severe infusion-related toxicities reported.

The therapy demonstrated a high overall response rate of 95% and a significant median plasma viral load reduction of 97% within 6 weeks, effectively treating refractory viral infections in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Posoleucel, an Allogeneic, Off-the-Shelf Multivirus-Specific T-Cell Therapy, for the Treatment of Refractory Viral Infections in the Post-HCT Setting. Pfeiffer, T., Tzannou, I., Wu, M., et al.[2023]

Adoptive transfer of virus-specific cytotoxic T lymphocytes (VSTs) has emerged as a promising immunotherapeutic approach to effectively combat viral infections after hematopoietic stem cell transplantation (HSCT), addressing the limitations of conventional antiviral drugs.

This method not only helps reconstitute antiviral immunity without causing graft-versus-host disease but also shows potential for broader application beyond individual patients and for treating other viral infections outside of HSCT contexts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reprint of: Virus-Specific T Cells: Broadening Applicability. Barrett, AJ., Prockop, S., Bollard, CM.[2020]

In a phase II clinical trial involving 38 patients, the use of banked virus-specific T cells (VSTs) showed a remarkable 92% overall response rate in treating severe viral infections after hematopoietic stem-cell transplantation, with complete responses for BKV and EBV infections.

The treatment was safe, with only two mild cases of graft-versus-host disease reported, and the VSTs demonstrated persistence for up to 12 weeks, providing broad antiviral protection against multiple viral pathogens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Off-the-Shelf Virus-Specific T Cells to Treat BK Virus, Human Herpesvirus 6, Cytomegalovirus, Epstein-Barr Virus, and Adenovirus Infections After Allogeneic Hematopoietic Stem-Cell Transplantation. Tzannou, I., Papadopoulou, A., Naik, S., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37910558/

Viral specific T cell therapy in kidney transplant recipients We describe our experience of using the virus-specific T cell therapy ... Results: Two cases of ADV infection resolved after one infusion of VSTs.

2. sciencedirect.com sciencedirect.com/science/article/pii/S1600613524003472

Virus-specific T cell therapy to treat refractory viral ... This minireview will explore challenges and controversies in treating viral OIs, competing VST production methods, recently reported and ongoing clinical ...

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 ... Virus-specific T cells are safe in patients with SCD following hematopoietic stem cell transplant. In patients with active viremia, ...

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

Virus-Specific T Cells for the Treatment of Systemic Infections ... This article provides a practical guide to VST therapy by reviewing manufacturing techniques, donor selection, and treatment indications.

5. aacrjournals.org aacrjournals.org/clincancerres/article/29/2/324/713977/Posoleucel-an-Allogeneic-Off-the-Shelf-Multivirus

Posoleucel, an Allogeneic, Off-the-Shelf Multivirus-Specific T ... , et al. Virus-specific T cells for adenovirus infection after stem cell transplantation are highly effective and class II HLA restricted.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36628536/

Posoleucel, an Allogeneic, Off-the-Shelf Multivirus-Specific T ... Posoleucel is a multivirus-specific T-cell therapy for off-the-shelf use against six viral infections that commonly occur in allo-HCT recipients.