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

Trial Summary

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.

What data supports the effectiveness of the treatment Viral Specific T-cells (VSTs) for post-transplant viral infections?

Research shows that Virus-Specific T-cell (VST) therapy can be effective for treating viral infections after hematopoietic cell transplantation (HCT), especially when conventional antiviral treatments fail. VSTs have been shown to work against multiple viruses without causing significant side effects like graft-versus-host disease, making them a promising option for patients with difficult-to-treat viral infections. ^{1 2 3 4 5}

Is Viral Specific T-cell therapy safe for humans?

Research shows that Viral Specific T-cell therapy, including treatments like Posoleucel, is generally safe for humans. In clinical trials, infusions were well-tolerated with minimal side effects, and only two mild cases of a condition called graft-versus-host disease were observed. ^{1 3 6 7 8}

How is the treatment Viral Specific T-cells (VSTs) different from other treatments for post-transplant viral infections?

Viral Specific T-cells (VSTs) are unique because they use immune cells from donors to specifically target and fight viral infections, offering a long-lasting solution without causing drug resistance or severe side effects like graft-versus-host disease. Unlike traditional antiviral drugs, which can be toxic and ineffective due to resistance, VSTs provide a targeted and effective approach, especially for infections that lack standard treatments. ^{1 2 5 8 9}

What is the purpose of this trial?

The purpose of this research study is to learn more about the use of viral specific T-lymphocytes (VSTs) to prevent or treat viral infections that may happen after allogeneic stem cell transplant. Allogeneic means the stem cells come from another person. VSTs are cells specially designed to fight viral infections that may happen after a stem cell transplant (SCT). Stem cell transplant reduces the body's ability to fight infections. Viral infections are a common problem after transplant and can cause significant complications. 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 a better way to treat these infections.

Research Team

Stella Davies, MBBS, PhD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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), 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 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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. Japan pubmed.ncbi.nlm.nih.gov

[Immunotherapy for refractory viral infections]. [2019]

3. United States 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. [2023]

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

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

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

Reprint of: Virus-Specific T Cells: Broadening Applicability. [2020]

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

Adoptive immunotherapy for primary immunodeficiency disorders with virus-specific T lymphocytes. [2023]

7. United States 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. [2022]

8. 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]

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

Virus-Specific T Cells: Broadening Applicability. [2021]