T-lymphocyte Therapy for Adenovirus Infections

(ADV-VSTS Trial)

Overseen By Melinda Triplet

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Nationwide Children's Hospital

Must not be taking: T-cell depleting drugs

Disqualifiers: HIV, Uncontrolled infection, Poor performance, others

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

Compensation: Varies

Number of Visits: 2

Duration: 1 day

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment using special immune cells called Adenovirus Specific T lymphocytes to address adenovirus infections. The researchers aim to determine if these cells, sourced from a patient's relative, can safely and effectively assist individuals who have struggled with other adenovirus treatments. Suitable candidates include those who have undergone a solid organ transplant, are currently battling an adenovirus infection unresponsive to other treatments, and have encountered issues with standard antiviral medications. As a Phase 1, Phase 2 trial, this research focuses on understanding the treatment's function in people and assessing its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but if you are taking CMX001 (brincidofovir), you must stop it at least 72 hours before the study treatment. Other investigational anti-adenoviral agents are not allowed during the study until Week 12.

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

Research has shown that using a specific type of immune cell, called T cells, is safe for treating adenovirus infections. These T cells have proven effective, especially for people with weakened immune systems. No major reports of serious side effects have emerged, indicating that the treatment is generally well-tolerated. Overall, the evidence is promising for those considering this treatment option. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for adenovirus infections?

Researchers are excited about adenovirus-specific T-lymphocyte therapy because it takes a novel approach by harnessing the body's own immune system to fight adenovirus infections. Unlike standard antiviral medications, which often broadly target viruses and can have limited effectiveness, this therapy uses tailored T-lymphocytes that specifically recognize and attack adenovirus-infected cells. This targeted action not only promises more effective clearing of the virus but also reduces the risk of harming healthy cells, potentially leading to fewer side effects. Additionally, because these T-lymphocytes are derived from haploidentical donors, the treatment could be more accessible for patients who might not respond to traditional antiviral drugs.

What evidence suggests that adenovirus-specific T lymphocytes might be an effective treatment for adenovirus infections?

Research has shown that special immune cells, called adenovirus-specific T cells, can effectively combat adenovirus infections, especially after stem cell transplants. One study found that about 80.6% of patients reduced or eliminated the virus after receiving these T cells. This indicates that the treatment helped clear the virus or significantly reduce its presence in the body. Patients tolerated the treatment well, experiencing no serious side effects. In this trial, participants in the "Recipient" arm will receive adenovirus-specific T lymphocytes to assess their effectiveness and safety. These positive results suggest that adenovirus-specific T cells could be a promising option for treating adenovirus infections. ^{1 6 7 8 9}

Who Is on the Research Team?

Eunkyung Song, MD

Principal Investigator

Nationwide Children's Hospital

Are You a Good Fit for This Trial?

This trial is for people with stubborn adenovirus infections who can't tolerate antiviral drugs due to kidney or bone marrow issues, or have had organ transplants. It's open to ages 0-60 and includes those on recent chemotherapy or immunosuppressants. Pregnant women and those with uncontrolled infections, HIV, or certain drug treatments are excluded.

Inclusion Criteria

Written informed consent and/or signed assent line from patient, parent or legal guardian prior to any study-related procedures.

Negative pregnancy test in female patients if applicable (childbearing potential)

I received an organ transplant more than 28 days ago.

Exclusion Criteria

I am currently taking a high dose of steroids.

I am on anti-fungal treatment and have shown improvement or stability for a week.

You have a known allergy to iron dextran.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Qualified patients receive ADV-VSTS infusion from haploidentical donors

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and efficacy, including viral load and adverse events

4 weeks

Weekly visits (in-person)

Long-term follow-up

Participants may continue to be monitored for long-term safety and efficacy

Ongoing

What Are the Treatments Tested in This Trial?

Interventions

• Adenovirus Specific T lymphocytes

Trial Overview The study tests adenovirus-specific T lymphocytes from related donors to see if they're safe and effective against tough-to-treat adenovirus infections. These special immune cells are prepared using a system that selects them based on their response to specific viral parts.

How Is the Trial Designed?

Group I: Recipient Experimental Treatment 1 Intervention

Recipient will undergo a screening period that will include history and physical examination, laboratory tests, performance status, HLA typing and pregnancy test (if needed). Qualified patients will receive ADV-VSTS infusion from haploidentical donors up to a maximum of 5.0 x 104 interferon gamma-negative cells/kg. All patients will be followed for laboratory and clinical response, safety, efficacy and tolerance.

Group II: Donor Active Control 1 Intervention

Donors will be evaluated to determine suitability to undergo apheresis collection and their infectious disease status. Donor evaluation will include history and physical examination, laboratory tests, FDA- approved donor testing of communicable diseases (HIV, HVB, HCV, HTLV-I, II, WNV, T. pallidum, T. cruzi, and Zika virus), ABO and Rh typing, pregnancy tests, and donor serology for ADV. Qualified donors will undergo leukapheresis. Collection will proceed for 2 hours or 2 blood volumes, whichever occurs first.

Who Is Running the Clinical Trial?

Nationwide Children's Hospital

Lead Sponsor

Trials

354

Recruited

5,228,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8525242/

Virus-specific T cells for adenovirus infection after stem ... Virus-specific T cells for adenovirus infection after stem cell transplantation are highly effective and class II HLA restricted.

2. ashpublications.org ashpublications.org/bloodadvances/article-abstract/5/17/3309/476675

Virus-specific T cells for adenovirus infection after stem cell ... Virus-specific T cells for adenovirus infection after stem cell transplantation are highly effective and class II HLA restricted.

3. astctjournal.org astctjournal.org/article/S2666-6367(23)02356-4/fulltext

Specific Cytotoxic T-Lymphocytes (CTLs) for Resistant ... Day 100 and 365 overall survival post-HSCT was 86.1% (CI95: 49.4-95.7) and 70.5% (CI95: 38.9-87.8), respectively (Figure 1). Among CR patients, ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1465324918300021

Adenovirus-specific T-lymphocyte efficacy in the presence ... About 80.6% of patients showed ad reduction or complete clearance of viral load concomitantly with in vivo expansion of VSTs and an acceptable tolerance profile ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04364178

Viral Specific T-Lymphocytes to Treat Adenovirus or CMV Reconstitution of anti-viral immunity by donor-derived cytotoxic T lymphocytes has shown promise in preventing and treating infections with adenovirus and CMV. ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2666636723023564

604 Adenoviral Cellular Therapy with Adenovirus (ADV)- ... Preliminary data affirm that donor ADV-specific CTLs are safe and effective in treating refractory ADV cases post-AlloHSCT.

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

Virus-Specific T Cells for the Treatment of Systemic Infections ... Multiple single-arm studies have suggested the potent clinical efficacy of VSTs for the treatment of refractory infections with EBV, CMV, ...

8. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/4836/505411/Treatment-of-Refractory-Adenovirus-ADV-Infections

Treatment of Refractory Adenovirus (ADV) Infections Using ... From the Viral Cytotoxic T-Lymphocyte Consortium (VIRCTLC), we present safety and efficacy results on immune compromised, AlloHSCT, or SOT ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11806872/

Adenovirus‐Specific T Cells in Adults Are Frequent, Cross‐ ... Adenovirus‐Specific T Cells in Adults Are Frequent, Cross‐Reactive to Common Childhood Adenovirus Infections and Boosted by Adenovirus‐Vectored ...