Donor T Cell Therapy for Adenovirus Infections

Overseen By David Marin, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

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

Disqualifiers: Uncontrolled infections, Active GVHD, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 2 weeks

16 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called donor T cell therapy for individuals with weakened immune systems who have adenovirus infections. The treatment uses special donor blood cells designed to combat the virus. The main goal is to determine if this treatment is safe and effective for immunocompromised individuals. Suitable candidates for this trial include those who have adenovirus in their system without symptoms or those with probable adenovirus disease. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative 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 you cannot participate if you are on certain high doses of prednisone or have recently received specific treatments like anti-thymocyte globulin or donor lymphocyte infusion.

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

Research has shown that Donor T Cell Therapy, also known as Virus-Specific T Cells (VSTs), is generally safe for treating adenovirus infections. Previous studies found that this therapy is well-tolerated, with very few side effects. These cells are specially designed to target and destroy viruses, aiding those with weakened immune systems who are at greater risk.

In studies, these donor T cells have been used successfully in patients, demonstrating both safety and effectiveness. As this is an early-stage trial, the primary goal is to identify any side effects. Overall, evidence suggests that Donor T Cell Therapy is a promising option with a good safety record. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard antiviral treatments for adenovirus infections, Donor T Cell Therapy uses specially prepared T cells from a healthy donor that are specifically targeted to the adenovirus. This therapy is unique because it harnesses the immune system's natural ability to fight off the virus, offering a potentially more effective and direct approach than traditional antivirals. Researchers are excited about this treatment because it could provide a faster response and be particularly beneficial for patients with weakened immune systems who struggle to fight off infections on their own.

What evidence suggests that donor T cell therapy might be an effective treatment for adenovirus infections?

Research has shown that donor T cell therapy, which participants in this trial will receive, could effectively treat adenovirus infections in people with weakened immune systems. One study demonstrated that these special virus-fighting cells worked well after stem cell transplants, with 81% of patients responding positively to the treatment. This indicates that most patients improved. The therapy uses cells from donors that are specially grown to find and destroy the virus. This targeted method helps the immune system combat the virus in those with weakened immune systems. Overall, early results suggest this therapy could be a strong option for addressing adenovirus infections. ^{1 2 3 5 6}

Who Is on the Research Team?

David Marin

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for immunocompromised patients with blood cancers and asymptomatic adenovirus viremia, or those showing probable or definitive signs of the disease. Participants must consent, not be pregnant, agree to use contraception if applicable, and cannot have certain uncontrolled infections or recent treatments that suppress the immune system.

Inclusion Criteria

I am not pregnant and willing to use birth control during the study.

I have a virus in my blood but feel fine, confirmed by tests.

I have been diagnosed with an adenoviral disease.

Exclusion Criteria

I am not currently taking high doses of prednisone, nor have I recently received specific immune treatments.

I have no worsening infections and am on treatment if I have any.

I have a severe reaction from a transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Treatment

Participants receive allogeneic adenovirus-specific cytotoxic T lymphocytes intravenously over 30 minutes. Additional infusions may be given at the discretion of the investigator.

2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety, efficacy, and persistence of the administered cells after treatment

12 months

Regular visits as per study protocol

What Are the Treatments Tested in This Trial?

Interventions

• Donor T Cell Therapy

Trial Overview The study tests donor T cell therapy using allogeneic adenovirus-specific cytotoxic T lymphocytes (CTLs) in patients with weakened immune systems due to blood cancers. These CTLs are grown from donated cells aimed at fighting off adenovirus infections.

How Is the Trial Designed?

Group I: Treatment (allogeneic adenovirus-specific CTLs) Experimental Treatment 1 Intervention

Within two weeks of enrollment, patients receive allogeneic adenovirus-specific CTLs IV over 30 minutes. Patients may receive additional allogeneic adenovirus-specific CTL infusions at the discretion of the investigator in the absence of disease progression or unacceptable toxicity.

Donor T Cell Therapy is already approved in United States, European Union for the following indications:

Approved in United States as Allogeneic Adenovirus-Specific Cytotoxic T Lymphocytes for:

• Adenovirus-related disease in immunocompromised patients

Approved in European Union as Donor-Derived Adenovirus-Specific CTLs for:

• Refractory adenovirus infections post allogeneic hematopoietic stem cell transplantation

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Adenoviruses are common but usually not dangerous for healthy individuals, while they can cause serious illness in immunocompromised patients, highlighting the need for effective treatments in these vulnerable groups.

The study suggests that using in vitro expanded virus-specific cytotoxic T lymphocytes (CTLs) could be a promising approach for treating or preventing adenovirus infections in immunosuppressed patients, as these T cells play a crucial role in controlling the virus in the body.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cell immunotherapy for adenoviral infections of stem-cell transplant recipients. Leen, AM., Myers, GD., Bollard, CM., et al.[2007]

In a study of 21 children with adenovirus (ADV) infection post-allogeneic stem cell transplantation (SCT), those who survived had detectable ADV-specific T cells, while all patients who experienced ADV-associated mortality lacked these protective T cells.

Children who successfully cleared ADV infection had significantly higher levels of ADV-specific T cells compared to those who did not get infected, suggesting that the presence of these T cells is crucial for protection against severe ADV infections after SCT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of adenovirus-specific T cells in children with adenovirus infection after allogeneic stem cell transplantation. Feuchtinger, T., Lücke, J., Hamprecht, K., et al.[2008]

In a phase 1/2 clinical trial involving 30 pediatric patients, ex vivo-generated virus-specific T cells (VSTs) demonstrated a high clinical response rate of 81% for treating adenoviral infections after hematopoietic stem cell transplantation, with 58% achieving complete response.

The study indicates that VSTs, whether derived from the stem cell donor or healthy third-party donors, are a safe and effective alternative to traditional antiviral treatments, which often have limited efficacy and significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Virus-specific T cells for adenovirus infection after stem cell transplantation are highly effective and class II HLA restricted. Rubinstein, JD., Zhu, X., Leemhuis, T., et al.[2022]

A clinical-grade method was developed to isolate and expand adenovirus-specific T cells from donors, yielding an average of 3.4 million specific T lymphocytes from peripheral blood or leukapheresis products, which is crucial for restoring immunity in patients with lymphopenia after stem cell transplantation.

The generated T cell lines demonstrated effective responses against adenovirus-infected cells and showed reduced alloreactive proliferation, indicating their potential for safe and effective adoptive immunotherapy in combating ADV infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolation and expansion of human adenovirus-specific CD4+ and CD8+ T cells according to IFN-gamma secretion for adjuvant immunotherapy. Feuchtinger, T., Lang, P., Hamprecht, K., et al.[2019]

Adoptive immunotherapy using virus-specific cytotoxic T cells (CTLs) from seropositive donors can effectively prevent severe viral infections in immunocompromised patients after hematopoietic stem cell transplantation (HSCT) or solid organ transplantation (SOT) without significant toxicity or increased risk of graft-versus-host disease (GvHD).

The study highlights the potential of using partially HLA-matched virus-specific CTLs from healthy seropositive individuals as an alternative source for T-cell therapy, especially when donor blood is not available, and emphasizes the need for a third-party T-cell donor registry to enhance treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive T-cell immunotherapy from third-party donors: characterization of donors and set up of a T-cell donor registry. Eiz-Vesper, B., Maecker-Kolhoff, B., Blasczyk, R.[2022]

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]

In a phase I/II study involving 14 patients who underwent umbilical cord blood transplantation, the infusion of adenovirus-specific T cells (ADV-VST) led to a 91% clearance of adenovirus load in patients with infections, demonstrating its efficacy as a treatment option.

The study found that while no new cases of graft versus host disease (GVHD) occurred in the first month post-infusion, reactivations of GVHD were observed in three patients, indicating a need for careful monitoring and potential immunosuppressive treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Curative or pre-emptive adenovirus-specific T cell transfer from matched unrelated or third party haploidentical donors after HSCT, including UCB transplantations: a successful phase I/II multicenter clinical trial. Qian, C., Campidelli, A., Wang, Y., et al.[2018]

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]

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. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2018-00929

Donor T Cell Therapy in Treating Immunocompromised ... This phase I trial studies the side effects of allogeneic adenovirus-specific cytotoxic T lymphocytes (donor T cell therapy) and to see how well they work ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2473952921004675

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. Author links ...

4. withpower.com withpower.com/trial/phase-1-adenoviridae-infections-2-2018-6f0a8

Donor T Cell Therapy for Adenovirus Infections In a phase 1/2 clinical trial involving 30 pediatric patients, ex vivo-generated virus-specific T cells (VSTs) demonstrated a high clinical response rate of 81% ...

5. nature.com nature.com/articles/s41467-024-47057-2

Antiviral cellular therapy for enhancing T-cell reconstitution ... This study highlights key clinical factors that impact response to VSTs and demonstrates the feasibility and efficacy of this therapy in pediatric HSCT.

6. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2017-0350.html

Administration of Off-the-Shelf, Expanded, Most Closely ... This phase I trial studies the side effects of allogeneic adenovirus-specific cytotoxic T lymphocytes (donor T cell therapy) and to see how well they work ...