Viral-Specific T-cell Therapy for Post-Transplant Viral Infections

Overseen By Naik Swati, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: St. Jude Children's Research Hospital

Must not be taking: Steroids, Thymoglobulin, Alemtuzumab

Disqualifiers: Active GVHD, Pregnancy, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 4 weeks

42 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called VST (Virus-Specific T-cells), which uses special T-cells to combat viral infections like CMV and ADV in patients who have undergone a stem cell transplant. The goal is to determine if these T-cells can reduce the virus in the blood and aid in safer, more effective recovery. The trial seeks patients who have had a transplant and still experience these infections despite treatment. Participants should not have severe infections or conditions requiring intensive medical support. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on steroids greater than 0.5 mg/kg prednisone equivalent, you may not be eligible to participate.

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

Research has shown that special immune cells, called virus-specific T cells (VSTs), have been safely used in other studies to treat viral infections after stem cell transplants. For instance, patients who received these cells for CMV, a common virus that can be dangerous post-transplant, experienced good results with few safety issues. Patients have tolerated these cells well, whether from donors or other sources.

In another study, VSTs helped patients with various viral infections, yielding promising results. The treatment was generally safe, with few serious side effects reported. This suggests that VSTs offer a promising option for safely managing challenging viral infections after a transplant. While no treatment is without risks, existing evidence indicates that patients in similar situations have tolerated VSTs well. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Viral-Specific T-cell Therapy (VST) because it offers a personalized approach to fighting post-transplant viral infections. Unlike traditional antiviral medications, which broadly target viruses, VST harnesses the power of the immune system by using T-cells specifically trained to recognize and attack virus-infected cells. This targeted action not only promises more effective viral control but also reduces the risk of harming healthy cells, potentially leading to fewer side effects. Additionally, VST could provide a solution for patients who do not respond well to standard antiviral treatments or who experience frequent relapses.

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

Research has shown that special immune cells called virus-specific T-cells (VSTs) can help treat viral infections like CMV and ADV after a transplant. In this trial, participants will be divided into two cohorts to receive VSTs. One study found that 80% of patients with active viral infections improved after receiving VSTs. These T-cells directly attack the viruses, reducing the virus levels in the body. Another study also found that VSTs are effective against several viruses, including CMV and ADV. Overall, VSTs have strong potential to reduce infections in transplant patients. ^{1 5 6 7 8}

Who Is on the Research Team?

Naik Swati, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

This trial is for patients who've had a specific type of bone marrow transplant and are struggling with CMV or ADV infections that haven't improved after two weeks of standard treatment. They should not have active GVHD, recent donor lymphocyte infusions, or be on high-dose steroids. Women must test negative for pregnancy and all participants need functioning major organs.

Inclusion Criteria

I am of childbearing age and my pregnancy test is negative.

My kidney function, measured by GFR, is above 60 mL/min.

I have a family member who is at least a half match for organ or tissue donation.

Exclusion Criteria

Pregnancy

I am currently experiencing symptoms of graft-versus-host disease.

I am unable to give consent by myself.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CMV- and ADV-specific T-cells infusion to treat infections post-transplant

4 weeks

1 visit (in-person) for infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment, including viral load reduction and adverse events

6 months

Regular visits (in-person) for monitoring

Long-term follow-up

Assess the persistence of response and long-term safety post-infusion

6 months

What Are the Treatments Tested in This Trial?

Interventions

• VST

Trial Overview

The study is testing if T-cells from donors can fight off stubborn CMV and ADV infections in post-transplant patients. These special cells are selected using an automated device called CliniMACS. The main goal is to see if the virus levels drop significantly within four weeks after getting these T-cells.

How Is the Trial Designed?

Group I: Cohort B Experimental Treatment 2 Interventions

Cohort B will include haploidentical donor who is different from the stem cell donor

Group II: Cohort A Experimental Treatment 2 Interventions

Cohort A will include haploidentical donor who is identical to the stem cell donor. The first 5 patients will be enrolled in Cohort A. If safety criteria are met, cohort B will be open for enrollment.

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

Approved in United States as VSTs for:

• Cytomegalovirus (CMV) infections after hematopoietic cell transplantation
• Adenovirus (ADV) infections after hematopoietic cell transplantation

Approved in European Union as VSTs for:

• Cytomegalovirus (CMV) infections after hematopoietic cell transplantation
• Adenovirus (ADV) infections after hematopoietic cell transplantation

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Published Research Related to This Trial

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 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 immunotherapy using virus-specific T cells (VSTs) has been shown to be a safe and effective treatment for viral infections in patients who have undergone hematopoietic stem cell transplantation (HSCT), with minimal toxicity and a low risk of graft versus host disease.

VSTs have demonstrated efficacy against several viral infections, including cytomegalovirus and Epstein-Barr virus, highlighting their potential as a therapeutic option during the immune deficient period following HSCT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Applications of virus-specific T cell therapies post-BMT. Motta, CM., Keller, MD., Bollard, CM.[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]

The study demonstrated the successful generation of virus-specific T cells (VSTs) that target 12 antigens from five different viruses, showing promise for treating infections in immunocompromised patients.

In a clinical trial involving 11 allogeneic transplant recipients, the VSTs were safe and resulted in a remarkable 94% response rate in managing active viral infections, with effects sustained over the long term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of broad-spectrum T cells as treatment for AdV, EBV, CMV, BKV, and HHV6 infections after HSCT. Papadopoulou, A., Gerdemann, U., Katari, UL., 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]

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]

Cytomegalovirus (CMV) infection is a significant concern after allogeneic hematopoietic stem cell transplant (HSCT), leading to increased morbidity and mortality, highlighting the need for effective treatments.

Adoptively transferred donor-derived virus-specific T (VST) cells show promise in early clinical trials for treating CMV, but logistical challenges in manufacturing and delivery need to be addressed to improve their widespread application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cellular Therapeutic Approaches to Cytomegalovirus Infection Following Allogeneic Stem Cell Transplantation. Shafat, MS., Mehra, V., Peggs, KS., et al.[2022]

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]

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