Virus Specific T-cell Therapy for Cytomegalovirus Infection

(ACES Trial)

Not currently recruiting at 32 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Pediatric Transplantation & Cellular Therapy Consortium

Must not be taking: Immunosuppressive antibodies, JAK inhibitors

Disqualifiers: Uncontrolled infections, Active malignancy, others

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

Compensation: Varies

Number of Visits: 1

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called virus-specific T-cell therapy to determine its safety and effectiveness in controlling viruses like CMV, EBV, and adenovirus. These viruses pose significant challenges for individuals who have undergone a stem cell transplant or have immune system issues. The trial targets those with these infections who have not responded to standard treatments or cannot tolerate them. Participants should have persistent viral issues after a transplant or due to a primary immune disorder. The goal is to manage these difficult infections with this new therapy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot be on certain immunosuppressive drugs or JAK inhibitors close to the time of enrollment. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that virus-specific T-cell therapy is likely to be safe for humans?

Research has shown that virus-specific T-cell (VST) therapy is generally safe for treating viral infections like cytomegalovirus (CMV). Studies have found that patients usually tolerate VST infusions well. For instance, one study revealed that patients who received VST therapy did not experience major side effects, such as worsening of graft-versus-host disease, where transplanted cells attack the recipient's body.

Another study demonstrated that VST therapy was both effective and safe, with 61% of patients responding positively, meaning most had good results without serious side effects. These findings suggest that VST therapy is a promising and relatively safe option for people dealing with ongoing viral infections, especially after a stem cell transplant. ^{1 2 3 4 5}

Why are researchers excited about this possible treatment for cytomegalovirus infection?

Unlike the standard antiviral drugs for cytomegalovirus (CMV) infection, which often focus on inhibiting viral replication, Virus Specific T-cell (VST) therapy uses a new approach by harnessing the body's immune system. VST therapy involves infusing specially prepared T-cells that are trained to recognize and attack not just CMV, but also other persistent viruses like adenovirus and Epstein-Barr virus. This therapy is exciting because it offers a targeted, multi-virus approach, potentially providing a more effective and long-lasting solution for patients whose infections persist despite conventional treatments. Researchers are hopeful that this tailored immune response will lead to better outcomes, especially in immunocompromised individuals.

What evidence suggests that virus-specific T-cell therapy is effective for controlling CMV infection?

Research has shown that special immune cells called virus-specific T cells (VSTs) may help treat cytomegalovirus (CMV) infections, especially in individuals who have undergone a stem cell transplant. In some studies, VSTs successfully managed infections from CMV, Epstein-Barr virus (EBV), and adenovirus, even when standard treatments failed. In this trial, participants will receive VSTs that are partially-HLA matched and activated using overlapping peptide libraries targeting these viruses. Patients treated with VSTs have experienced good results with few side effects. This therapy uses T cells specially trained to find and fight certain viruses. These findings suggest that VSTs could effectively manage tough viral infections in people with weakened immune systems. ^{1 2 6 7 8}

Who Is on the Research Team?

Michael Pulsipher, MD

Principal Investigator

Children's Hospital Los Angeles

Michael Keller, MD

Principal Investigator

Children's National Research Institute

Are You a Good Fit for This Trial?

This trial is for patients who've had a stem cell transplant or have primary immunodeficiency with persistent or relapsed CMV, EBV, or adenovirus infections despite standard treatment. Eligible participants must be able to reduce steroid use and not be pregnant if applicable. Those with uncontrolled cancer, recent monoclonal antibody therapy, other cellular therapies, or uncontrolled infections are excluded.

Inclusion Criteria

Treatment of the following persistent or relapsed infections despite standard therapy:

- CMV: Treatment of persistent or relapsed CMV disease or infection after standard therapy. For CMV infection, standard therapy is defined as antiviral therapy with ganciclovir, foscarnet or cidofovir for at least 14 days.

- Adenovirus: Treatment of persistent or relapsed adenovirus infection or disease despite standard therapy. Standard therapy is defined as antiviral therapy with cidofovir or brincidofovir.

Exclusion Criteria

Patients with active and uncontrolled relapse of malignancy (if applicable).

Patients receiving ATG, Campath, Basiliximab or other immunosuppressive monoclonal antibodies targeting T-cells within 28 days of screening for enrollment.

Patients who have received donor lymphocyte infusion (DLI) or other experimental cellular therapies within 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive partially-HLA matched allogeneic multivirus-specific VSTs to evaluate safety and antiviral activity

4 weeks

1 visit (in-person) for VST infusion

Follow-up

Participants are monitored for safety and effectiveness after VST infusion, including viral load and immune response assessments

3 months

Regular monitoring visits

Long-term follow-up

Overall survival and persistence of infused VSTs are monitored

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Virus Specific T-cell (VST)

Trial Overview The study tests the safety and effectiveness of virus-specific T-cell (VST) infusions in controlling EBV, CMV, and adenovirus infections in individuals post-stem cell transplant or those with primary immunodeficiency disorders who haven't responded well to standard treatments.

How Is the Trial Designed?

Group I: Virus specific T cell lines (VSTs) against three viruses Experimental Treatment 1 Intervention

The study will evaluate whether partially-HLA matched allogeneic multivirus-specific VSTs, activated using overlapping peptide libraries spanning immunogenic antigens from CMV, adenovirus and EBV, will be safe and produce anti-viral effects in immunodeficient recipients infected with one of more of the targeted viruses that are persistent despite conventional anti-viral therapy.

Who Is Running the Clinical Trial?

Pediatric Transplantation & Cellular Therapy Consortium

Lead Sponsor

Michael Pulsipher, MD

Lead Sponsor

Trials

5

Recruited

240+

Citations

1. academic.oup.com academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaf232/8125789

Virus-Specific T-Cell Therapy for Prophylaxis and Treatment of ... Virus-specific T cells (VSTs) have been used for the prophylaxis and treatment of CMV infections. We conducted a scoping review to catalogue and characterize ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7411136/

Cellular Therapeutic Approaches to Cytomegalovirus Infection ... We will discuss how the VST field has improved outcomes for many patients with life threatening viral infection following HSCT and explore how to broaden the ...

3. ashpublications.org ashpublications.org/bloodadvances/article/8/14/3813/516362/Incidence-and-outcomes-of-cytomegalovirus

Incidence and outcomes of cytomegalovirus reactivation after ... CMV reactivation is a common complication of CAR T-cell therapy and is associated with increased overall mortality.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02982902

T Cell Therapy of Opportunistic Cytomegalovirus Infection The primary objective of this study is to determine the feasibility of the treatment of opportunistic cytomegalovirus (CMV) infections after hematopoietic stem ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2452318625000261

Multidimensional evaluation of CMV-specific T Cells Adoptive immunotherapy with CMV-specific T cells (CMV-VSTs) has shown favorable efficacy and minimal adverse effects in clinical settings, ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40327446/

Virus-specific T-cell therapy for prophylaxis and treatment ... Virus-specific T-cells (VST) have been used for the prophylaxis and treatment of CMV infections. We conducted a scoping review to catalogue and characterize ...

7. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/10309/489554/Viral-Specific-T-Cell-Therapy-for-Cytomegalovirus

Viral-Specific T Cell Therapy for Cytomegalovirus Infection ... In terms of efficacy, 14 patients responded to Viro-T-cell for a probability of response at week 8 of 61.18% (95%CI 34.50-79.69) (Figure1). None ...

8. karger.com karger.com/tmh/article/52/1/5/913601/Virus-Specific-T-Cell-Therapy-for-the-Management

Virus-Specific T-Cell Therapy for the Management of Viral ... The infusions were generally safe, without exacerbations of GvHD, and were associated with clinical benefit that coincided with CMV-specific ...