VST Therapy for Post-Transplant Viral Infections

(NATS Trial)

Not currently recruiting at 1 trial location

Overseen By Fahmida Hoq, MBBS, MS

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Children's National Research Institute

Must not be taking: ATG, Campath, Basiliximab, others

Disqualifiers: Uncontrolled infections, GVHD, malignancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment using Virus Specific T cells (VSTs) to assist individuals who have undergone a stem cell transplant and are facing certain viral infections. It targets infections that have not improved after two weeks of standard treatment or those at risk of such infections. The trial consists of two parts: one for prevention and another for treating active infections. Participants should have received a stem cell transplant and be dealing with viruses like CMV or EBV that impact daily life. The study aims to determine the safety and effectiveness of these special T cells at various dosage levels. As a Phase 1 trial, the research focuses on understanding how the treatment functions in people, offering participants a chance to be among the first to receive this new therapy.

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 require that steroids be tapered to less than 0.5 mg/kg/day of prednisone or equivalent. Also, you cannot have received certain immunosuppressive drugs or investigational products within 28 days before the infusion.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that virus-specific T cells (VSTs) have been safely used in patients who underwent stem cell transplants. In past studies, VSTs from donors or other sources helped control viral infections in both children and adults without causing serious harm. Any side effects that occurred were usually mild and easily treatable.

One study examined the use of VSTs for severe viral infections after stem cell transplants and found them to be well-tolerated. Another report noted that any side effects were minor and manageable with standard care. VSTs were also used safely in patients with sickle cell disease after transplants, showing good results even in those with active viral infections.

Overall, the evidence suggests that VST therapy is generally safe for managing viral infections in transplant patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Virus Specific T cells (VSTs) because they offer a personalized approach to tackling viral infections after a hematopoietic stem cell transplant (HSCT). Unlike standard antiviral medications, which generally target the virus itself, VSTs are tailored immune cells that specifically recognize and attack virus-infected cells, potentially providing a more precise and effective defense. This targeted mechanism could result in fewer side effects compared to conventional treatments, as it spares healthy cells. Additionally, VSTs have the potential to offer faster and more durable protection against multiple viruses simultaneously, a significant advantage for patients with weakened immune systems post-transplant.

What evidence suggests that this trial's treatments could be effective for post-transplant viral infections?

Research has shown that special immune cells called virus-specific T cells (VSTs) can help treat viral infections in people who have had stem cell transplants. In previous studies, 80% of patients with active viral infections improved after receiving VSTs. Typically, patients see reductions in viral load and symptom relief within 1 to 2 weeks of treatment, with long-lasting benefits. VSTs have proven effective against infections like CMV, EBV, and adenovirus, among others. In this trial, participants will receive VSTs for both prophylactic and treatment purposes. These treatments are generally safe and can help control infections while the patient's immune system strengthens. ^{1 2 6 7 8}

Who Is on the Research Team?

Michael D Keller, MD

Principal Investigator

Children's National Research Institute

Are You a Good Fit for This Trial?

This trial is for patients who've had a bone marrow or stem cell transplant and are at risk of, or currently have, certain viral infections (like EBV, CMV) that haven't improved after standard treatment. They should be relatively stable with no severe GVHD, uncontrolled cancer relapse, or recent use of other investigational drugs.

Inclusion Criteria

I am able to reduce my steroid use to less than 0.5 mg/kg/day.

I am able to perform most of my daily activities.

I have a treatment involving immune cells ready for use.

Exclusion Criteria

I have moderate to severe graft-versus-host disease.

I haven't had cell therapy, except for transplant-related ones, in the last 28 days.

I haven't received specific immune-suppressing drugs in the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Virus Specific T cells (VSTs) for prophylactic and treatment of active viral infection(s) after HSCT

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including incidence of acute GvHD and adverse events

45 days

Long-term Follow-up

Reconstitution of Antiviral Immunity and monitoring of antiviral response

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Virus Specific T cells (VSTs)

Trial Overview The trial tests Virus Specific T cells (VSTs) from donors to see if they're safe and can prevent or treat viral infections in people who received allogeneic hematopoietic stem cell transplants. It has two parts: one for prevention and another for active infection treatment.

How Is the Trial Designed?

Group I: Prophylactic and treatment Experimental Treatment 1 Intervention

Virus Specific T cells (VSTs) for prophylactic and treatment of active viral infection(s) after HSCT. 3 different dose levels starting with 1 x 10E7 /m2 (a T cell number more than an order of magnitude lower than that administered at the time of an unmanipulated marrow infusion), followed by 2 x 10E7/m2 and a final dose 5 x 10E7 VSTs/m2

Who Is Running the Clinical Trial?

Children's National Research Institute

Lead Sponsor

Trials

227

Recruited

258,000+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Adoptive immunotherapy using virus-specific cytotoxic T cells (VSTs) has significantly advanced over the past 30 years, providing a promising method to restore immunity against viral infections after organ transplants, particularly for common pathogens like cytomegalovirus and Epstein-Barr virus.

Recent improvements in the manufacturing process of pathogen-specific T cells (pSTs) have made it possible to produce these cells more efficiently and even allow for off-the-shelf options, enhancing their availability for treating infections and related malignancies in transplant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathogen-specific T Cells: Targeting Old Enemies and New Invaders in Transplantation and Beyond. Papadopoulou, A., Alvanou, M., Karavalakis, G., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10196792/

Outcomes following posttransplant virus-specific T-cell ... Virus-specific T cells are safe in patients with SCD following hematopoietic stem cell transplant. In patients with active viremia, 80% achieved remission ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36736781/

Third-Party and Patient-Specific Donor-Derived Virus ... Our data suggest that TP VSTs may be sufficient to control viral infection until immune reconstitution occurs despite the potential for more ...

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

Virus-Specific T Cells for the Treatment of Systemic Infections ... Improvement of viral load and/or symptoms is typically observed within 1–2 weeks from VST infusion. Responses are generally durable, with only ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1600613524002806

Third-party virus-specific T cells for the treatment of double- ... Virus-specific T cells (VSTs) have been shown to be an effective treatment for infections with ADV, BKPyV, cytomegalovirus (CMV), and Epstein-Barr virus (EBV).

5. ashpublications.org ashpublications.org/bloodadvances/article/6/9/2897/483801/Scheduled-administration-of-virus-specific-T-cells

Scheduled administration of virus-specific T cells for viral ... In conclusion, scheduled VSTs appear to be safe and potentially effective at limiting serious complications from viral infections after ...

6. 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 ...

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. 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, ...