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

Overseen by Naik Swati, MD

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: St. Jude Children's Research Hospital

Must not be taking: Steroids, Thymoglobulin, Alemtuzumab

Disqualifiers: Active GVHD, Pregnancy, others

No Placebo Group

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

The investigators want to learn if CMV- and ADV-specific T-cells (cells that fight infections) isolated (selected) from a donor using an automated medical device can be a safe treatment for treating patients with CMV, and ADV after transplant.This study will test the effects and safety of giving VSTs produced here at St. Jude in treating the participant's infection. Primary objective To determine the efficacy of VSTs to achieve a ≥1 log10 reduction in CMV and/or ADV viral load in the peripheral blood 4 weeks after VST infusion. When the initial viral load is \<1 log10 above the threshold of detection, the objective is to achieve a reduction to below the threshold of detection. Secondary objectives * Determine the safety of VSTs when used to treat CMV and/or ADV viremia post-HCT. * Determine the proportion of patients who achieve a negative viral load at 3 months post-infusion. * Assess the persistence of response for 6 months post-infusion.

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.

What data supports the effectiveness of the treatment VST for post-transplant viral infections?

Research shows that virus-specific T cells (VSTs) can help restore the body's ability to fight off viral infections after a transplant, especially when other treatments fail. This approach has improved outcomes for patients with serious viral infections after stem cell transplants, without causing harmful side effects like graft-versus-host disease. ^{1 2 3 4 5}

Is virus-specific T-cell therapy safe for humans?

Virus-specific T-cell therapy has been shown to be safe in humans, with studies reporting minimal side effects and low risk of complications like graft vs host disease (a condition where transplanted cells attack the recipient's body). ^{4 5 6 7 8}

How is the VST treatment different from other treatments for post-transplant viral infections?

VST treatment is unique because it uses virus-specific T-cells to restore the body's ability to fight viral infections after a transplant, without causing drug resistance or severe side effects like graft-versus-host disease. Unlike traditional antiviral drugs, which can be toxic and expensive, VSTs offer a more targeted and potentially long-lasting solution by directly enhancing the immune response. ^{1 2 5 9 10}

Research Team

Naik Swati, MD

Principal Investigator

St. Jude Children's Research Hospital

Eligibility Criteria

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

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

Pregnancy

I am unable to give consent by myself.

Trial Timeline

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

Treatment Details

Interventions

• VST (Virus Therapy)

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.

Participant Groups

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.

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Dr. James R. Downing

St. Jude Children's Research Hospital

Chief Executive Officer since 2014

MD from University of Michigan Medical School

Dr. Ellis J. Neufeld

St. Jude Children's Research Hospital

Chief Medical Officer since 2017

MD, PhD from Harvard Medical School

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

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

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

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

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

3. England pubmed.ncbi.nlm.nih.gov

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

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

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

6. Switzerland pubmed.ncbi.nlm.nih.gov

Cellular Therapeutic Approaches to Cytomegalovirus Infection Following Allogeneic Stem Cell Transplantation. [2022]

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

Activity of broad-spectrum T cells as treatment for AdV, EBV, CMV, BKV, and HHV6 infections after HSCT. [2022]

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

Applications of virus-specific T cell therapies post-BMT. [2023]

9. Japan pubmed.ncbi.nlm.nih.gov

[Immunotherapy for refractory viral infections]. [2019]

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

T cells for viral infections after allogeneic hematopoietic stem cell transplant. [2021]