T-Lymphocytes for Viral Infections

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Jessie L. Alexander

Must not be taking: ATG, Alemtuzumab

Disqualifiers: Acute GVHD, Chronic GVHD, Pregnancy, others

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

Compensation: Varies

Number of Visits: 5

Duration: Up to 5 infusions with a minimum of 14-day intervals

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial studies a new treatment approach using specific immune cells (T-lymphocytes) to combat viral infections like adenovirus, CMV, and EBV in individuals with weakened immune systems. These infections commonly affect those who have undergone organ transplants or face immune challenges. The trial aims to determine if these tailored immune cells can safely and effectively treat stubborn infections that resist standard treatments. Individuals who have had a transplant or have immune issues and are dealing with persistent infections despite regular treatment might be suitable candidates for this trial. As a Phase 1, Phase 2 trial, this research focuses on understanding the treatment's function in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking medical advancements.

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 mentions that your steroid dose should be reduced to less than 1 mg/kg/day of prednisone (or equivalent) before receiving the cellular infusion.

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

Previous studies have shown that special immune cells, called virus-specific T-cells, hold promise in treating infections like adenovirus, CMV (cytomegalovirus), and EBV (Epstein-Barr virus). Research suggests that these T-cells can help fight these viruses, especially in individuals with weakened immune systems.

Safety data from earlier trials are encouraging. One study found that these T-cells were generally well-tolerated by patients, with most side effects being mild, such as temporary fever or chills after treatment.

These treatments are still undergoing testing to ensure efficacy and safety. However, the evidence so far suggests they could be a viable option for those struggling to combat these viral infections. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these T-Lymphocyte treatments because they offer a targeted approach to fighting viral infections like adenovirus, cytomegalovirus, and Epstein-Barr virus. Unlike standard antiviral drugs that can be broad and less specific, these treatments harness the power of the body's own immune cells, specifically trained to attack these viruses. The unique mechanism involves collecting and stimulating donor T-cells with viral antigens, then selecting those that secrete interferon gamma, which enhances their virus-fighting capabilities. This approach not only aims for precision in targeting the infection but also promises faster and potentially more effective results compared to traditional treatments.

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

Research has shown that certain immune cells, called viral-specific T-lymphocytes, can help fight infections like adenovirus, CMV, and EBV, especially in people with weakened immune systems. In past studies, researchers created these T cells to target specific parts of these viruses, and they showed promise in both preventing and treating these infections. For instance, researchers safely and effectively used them to treat ongoing adenovirus infections by employing a special production method. In this trial, participants will receive viral-specific T-lymphocytes, which have also helped patients who underwent stem cell transplants by rebuilding their ability to fight viruses. Overall, evidence suggests that viral-specific T-lymphocytes could be a promising treatment option for those dealing with these viral infections. ^{1 2 4 5 6}

Who Is on the Research Team?

Jessie Alexander, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for people with weakened immune systems due to a transplant or other reasons, who are battling infections from adenovirus, CMV, or EBV. Participants must have had an allogeneic HCT or solid organ transplant, or have compromised immunity and not responded well to standard treatments.

Inclusion Criteria

I have a persistent Adenovirus, CMV, or EBV infection despite treatment.

I, or my guardian, have signed the consent form. If I'm over 7, I've also agreed to participate.

I am between 1 month and 65 years old.

Exclusion Criteria

Patients who are pregnant or lactating.

Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks to participation in the study, may interfere with the participant's ability to comply with study requirements, or that may impact the quality or interpretation of the data obtained from the study.

I received specific immune treatments recently and my T cell count is very low.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive viral specific T-Lymphocytes infusion to treat infection with adenovirus, CMV, or EBV

Up to 5 infusions with a minimum of 14-day intervals

Up to 5 visits (in-person)

Follow-up

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

6 months post initial infusion, with additional 90 days if further infusions are received

Regular visits as per monitoring schedule

Data Abstraction

Data may be abstracted from subjects' medical charts for an additional 1 year after the most recent infusion

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Adenovirus Specific T-Lymphocytes
• Cytomegalovirus Specific T-Lymphocytes
• Epstein-Barr Virus Specific T-Lymphocytes

Trial Overview The study tests if T-cells that target specific viruses can fight off infections by adenovirus, CMV, and EBV in patients with weak immunity. It's a phase I/II trial using gamma capture technology to create these T-cells quickly and more affordably than current methods.

How Is the Trial Designed?

Group I: Viral Specific T-Lymphocytes Experimental Treatment 3 Interventions

Peripheral blood mononuclear cells will be collected from the donor and loaded onto our Miltenyi Biotec CliniMACS® Plus where they will be stimulated in vitro with viral-specific antigen(s). The cells are then immunomagnetically labeled with interferon gamma via the cytokine capture system. By this method, viral specific, gamma-secreting T cells, are captured in a closed, sterile system.

Who Is Running the Clinical Trial?

Jessie L. Alexander

Lead Sponsor

Trials

1

Recruited

30+

Published Research Related to This Trial

Cytomegalovirus (CMV) reactivation poses significant risks for immunocompromised patients, such as those undergoing hematopoietic progenitor cell transplantation or living with HIV, leading to severe health complications despite antiviral treatments.

Recent advances in immunotherapy, including the adoptive transfer of CMV-specific T cell clones from seropositive donors, show promise in enhancing CMV-specific immunity and effectively treating CMV reactivation in these vulnerable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive immunotherapy for cytomegalovirus (CMV) disease in immunocompromised patients. Lim, JB., Kwon, OH., Kim, HS., et al.[2005]

Virus-specific T cells can effectively target multiple pathogens in patients who have undergone hematopoietic stem cell transplantation, showing promise against viruses like cytomegalovirus and Epstein-Barr Virus.

The potential to target additional pathogens such as BK virus, JC virus, and Zika virus suggests that this therapy could be expanded to improve patient outcomes, especially with the development of patient-specific and third-party T cell products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pipeline of antiviral T-cell therapy: what's in the clinic and undergoing development. Fatic, A., Zhang, N., Keller, MD., et al.[2022]

Adoptive immunotherapy using virus-specific T lymphocytes can effectively restore immunity against cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus (ADV) without causing acute toxicity or increasing the risk of graft-versus-host disease, making it a safe treatment option.

In a study of 204 healthy donors, significant variations in T cell frequencies were found, with 100% of CMV-seropositive donors showing specific T cells, indicating that targeting specific antigens like CMVpp65 and EBVBZLF1 could enhance the efficacy of immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CMV-, EBV- and ADV-specific T cell immunity: screening and monitoring of potential third-party donors to improve post-transplantation outcome. Sukdolak, C., Tischer, S., Dieks, D., et al.[2013]

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]

A new method allows for the rapid generation of virus-specific T cells targeting EBV, CMV, and adenovirus in just 2-3 weeks without using infectious viruses, making the process simpler and more accessible.

In a study involving 12 transplant recipients with active viral infections, 80% achieved complete virological responses, with no immediate or delayed toxicities observed, indicating both safety and efficacy of this T cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and clinical efficacy of rapidly-generated trivirus-directed T cells as treatment for adenovirus, EBV, and CMV infections after allogeneic hematopoietic stem cell transplant. Gerdemann, U., Katari, UL., Papadopoulou, A., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06909110

NCT06909110 | Viral Specific T-Lymphocytes to Treat ... Reconstitution of anti-viral immunity by donor-derived cytotoxic T lymphocytes has shown promise in preventing and treating infections with adenovirus, CMV, and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3692015/

Expansion of T cells targeting multiple antigens of ... We have shown that after 18 days in culture we can generate T cells that target multiple epitopes from at least two antigens of CMV, EBV and Ad.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118718089

Safety and Efficacy of Virus-Specific Cytotoxic T- ... Safety and efficacy of virus-specific cytotoxic T-lymphocytes manufactured by the IFN-g cytokine capture system for the treatment of refractory adenovirus.

4. trialx.com trialx.com/clinical-trials/listings/306861/viral-specific-t-lymphocytes-to-treat-infection-with-adenovirus-cytomegalovirus-or-epstein-barr-virus-in-patients-with-compromised-immunity/

Viral Specific T-Lymphocytes to Treat Infection With ... Viral Specific T-Lymphocytes to Treat Infection With Adenovirus, Cytomegalovirus or Epstein-Barr Virus in Patients With Compromised Immunity.

5. academic.oup.com academic.oup.com/cid/article/81/4/e218/8125789

Virus-Specific T-Cell Therapy for Prophylaxis and Treatment of ... Cytomegalovirus-specific T cells have been used in studies of primarily adult hematopoietic stem cell transplant recipients.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10383098/

Virus-Specific T-Cell Therapy for Viral Infections of the Central ... Virus-specific T-cells are increasingly perceived as a principled and valuable tool to treat opportunistic viral infections.