T-cell Therapy for Viral Infections

Recruiting at 2 trial locations

Overseen By Jamie Wilhelm

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Hospital Medical Center, Cincinnati

Must not be taking: ATG, Alemtuzumab

Disqualifiers: GVHD, Uncontrolled infection, Relapse, 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: 1

Duration: 4 weeks

750 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a special type of white blood cell, called viral specific T-cells (VSTs), can be safely administered to patients to combat viral infections. The treatment uses T-cells from a donor to enhance the immune system. Suitable candidates for this trial include individuals with weakened immune systems facing a viral infection or its reactivation. Participants must be able to receive treatment in Cincinnati. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that your clinical status must allow for tapering (gradually reducing) of steroids to less than 0.5mg/kg of prednisone or an equivalent steroid.

Is there any evidence suggesting that Viral Specific T-cells (VSTs) are likely to be safe for humans?

Research has shown that Viral Specific T-cells (VSTs) are generally safe for people. Studies have found that side effects from VST therapy are usually mild and easily treatable. If side effects occur, they can often be managed without much trouble. One study found that both donor-derived and third-party VSTs were safe for children with viral infections after stem cell transplants, indicating a positive safety profile for VSTs.

Although this study is still in its early stages, the testing of VSTs in later-stage trials suggests a high level of safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Viral Specific T-cells (VSTs) are unique because they represent a tailored approach to fighting viral infections by using specially trained immune cells. Unlike standard treatments that might rely on antiviral drugs to inhibit virus replication, VSTs directly target and eliminate infected cells, providing a more precise and potentially more effective response. Researchers are excited about VSTs because they harness the body's own immune system, offering a potential long-lasting defense without the side effects associated with traditional antiviral medications. This innovative approach could lead to faster recovery and improved outcomes for patients battling stubborn viral infections.

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

Research has shown that virus-specific T-cells (VSTs) offer a promising treatment for viral infections, especially when other antiviral treatments fail. Studies have found that VSTs can effectively locate and destroy viruses in the body. In this trial, participants will receive posoleucel, a ready-to-use therapy targeting multiple viruses, including adenovirus and BK virus. These treatments, derived from healthy donors, are designed to partially match patients, aiding them in fighting off several viruses simultaneously. Early results suggest that VSTs can safely support the immune system in managing challenging viral infections. ^{2 4 6 7 8}

Who Is on the Research Team?

Michael Grimley, MD, MD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Are You a Good Fit for This Trial?

This trial is for immunocompromised patients of any age with viral infections, especially those who've had a stem cell transplant at least 21 days prior. Participants must be able to reduce steroid use and travel to Cincinnati for the infusion. It's not suitable for individuals with active acute GVHD grades II-IV, uncontrolled bacterial/fungal infections, cancer relapse, or recent ATG/alemtuzumab infusions.

Inclusion Criteria

I can go to Cincinnati for a CTL infusion treatment.

Immunocompromised patient with evidence of viral infection or reactivation

Informed consent obtained by PI or sub-investigator either in person or by phone

Exclusion Criteria

I am experiencing moderate to severe symptoms from a recent transplant.

I do not have any untreated bacterial or fungal infections.

My cancer has returned and is not under control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive third party viral specific T-cell (VST) infusions

4 weeks

1 visit (in-person) for infusion

Follow-up

Participants are monitored for safety, effectiveness, and infusional toxicity after treatment

4 weeks

Regular monitoring visits

What Are the Treatments Tested in This Trial?

Interventions

• Viral Specific T-cells (VSTs)

Trial Overview The study tests if T-cells from an unrelated donor can safely treat viral infections in immunocompromised patients. These special white blood cells are designed to fight specific viruses and will be infused into participants to see if they help control the infection.

How Is the Trial Designed?

Group I: Viral Specific VST Infusion Experimental Treatment 1 Intervention

3rd party VST infusion

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+

Published Research Related to This Trial

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]

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]

The study successfully produced virus-specific T cells (VST) in 100% of cases using the CliniMACS Prodigy® system, demonstrating a feasible and automated method for therapy that could enhance scalability.

In a retrospective analysis of 26 patients with viral diseases post-hematopoietic stem cell transplantation, VST therapy showed a 77% response rate, significantly improving overall survival for responders compared to non-responders (P<0.001), with a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automated production of specific T cells for treatment of refractory viral infections after allogeneic stem cell transplantation. Heinz, AT., Calkoen, FGJ., Derbich, A., et al.[2023]

A new method for generating virus-specific T cells (VSTs) using peripheral blood mononuclear cells (PBMCs) in serum-free medium allows for the targeting of multiple viruses, including CMV and EBV, without the need for complex preparation of antigen-presenting cells.

This simplified approach not only matches the effectiveness of traditional methods but also reduces costs and variability, making it more suitable for clinical use, especially for immunocompromised patients like those receiving hematopoietic stem cell transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generation of multivirus-specific T cells by a single stimulation of peripheral blood mononuclear cells with a peptide mixture using serum-free medium. Nishiyama-Fujita, Y., Kawana-Tachikawa, AI., Ono, T., et al.[2019]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10383098/

Virus-Specific T-Cell Therapy for Viral Infections of the Central ... Virus-specific T-cells are increasingly perceived as a principled and valuable tool to treat opportunistic viral infections.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0006497121037241

Posoleucel (ALVR105), an Off-the-Shelf, Multivirus-Specific ... Posoleucel is an ex-vivo expanded, partially HLA-matched, off-the-shelf, multivirus-specific T cell investigational product generated from healthy, third-party ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38597860/

Phenotypic and functional characterization of posoleucel, a ... Posoleucel is an off-the-shelf multivirus-specific T cell investigational product for the treatment and prevention of infections due to adenovirus, BK virus, ...

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 ... In the absence of safe and effective antiviral treatments, virus-specific T cells have emerged as a promising therapeutic option. Posoleucel is ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05305040

Study of Posoleucel (ALVR105,Viralym-M) for Multi-Virus ... This is a Phase 3 study to evaluate posoleucel (ALVR105, Viralym-M); an allogeneic, off-the-shelf multi-virus specific T cell therapy that targets six viral ...

7. 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.

8. 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 ...