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 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 in treating patients with a weakened immune system (immunocompromised) and adenovirus-related disease. Allogeneic adenovirus-specific cytotoxic T lymphocytes are made from donated blood cells grown in the laboratory and are designed to kill viruses that can cause infections in immunocompromised patients with adenovirus-related disease.

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 Donor T Cell Therapy for Adenovirus Infections safe for humans?

Research indicates that Donor T Cell Therapy, also known as Virus-Specific T Cells (VSTs), is generally safe for treating adenovirus infections in humans, especially in those with weakened immune systems. Studies have shown that this therapy can effectively manage viral infections without significant acute toxicity or increased risk of graft-versus-host disease (a condition where donor cells attack the recipient's body). ^{1 2 3 4 5}

How is Donor T Cell Therapy different from other treatments for adenovirus infections?

Donor T Cell Therapy is unique because it uses virus-specific T cells from a donor to help the patient's immune system fight adenovirus infections, especially in those with weakened immune systems after stem cell transplants. Unlike traditional antiviral drugs, which can have limited effectiveness and significant side effects, this therapy directly boosts the body's ability to target and eliminate the virus. ^{1 2 4 6 7}

What data supports the effectiveness of the treatment Donor T Cell Therapy for adenovirus infections?

Research shows that using virus-specific T cells (VSTs) to treat adenovirus infections in patients who have had stem cell transplants is highly effective, with 81% of patients showing improvement and 58% achieving complete recovery. This approach is particularly beneficial for those with weakened immune systems, as traditional antiviral drugs often have limited success and can cause significant side effects. ^{1 2 6 7 8}

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

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]

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]

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]

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]

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

Virus-specific T cells for adenovirus infection after stem cell transplantation are highly effective and class II HLA restricted. [2022]

2. Netherlands 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. [2019]

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

T-cell immunotherapy for adenoviral infections of stem-cell transplant recipients. [2007]

4. England pubmed.ncbi.nlm.nih.gov

Detection of adenovirus-specific T cells in children with adenovirus infection after allogeneic stem cell transplantation. [2008]

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

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

6. Switzerland 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. [2022]

7. England 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. [2018]

8. England pubmed.ncbi.nlm.nih.gov

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