CMV-specific T Cells for CMV Infection

Age: < 65

Sex: Female

Trial Phase: Academic

Sponsor: University of Calgary

Must not be taking: Steroids, Antimetabolites, Checkpoint inhibitors, others

Disqualifiers: Steroid use, Antimetabolites, Checkpoint inhibitors, others

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

Compensation: Varies

Number of Visits: 9

Duration: Until discharge from inpatient unit

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with a specific immune system problem and a cytomegalovirus (CMV) infection. The treatment, called CMV-VST, uses special donor cells to combat the virus. It targets those with a severe immune issue who also have CMV in their blood and pneumonia. The trial excludes participants taking certain medications that affect the immune system. As an unphased trial, it provides a unique opportunity to contribute to groundbreaking research that could lead to new treatment options.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking certain medications, like high doses of steroids, specific immunosuppressants, and checkpoint inhibitors, before participating. If you're on these, you may need to stop them before joining the trial.

What prior data suggests that CMV-specific donor-derived T lymphocytes (CMV-VST) are safe?

Research has shown that using CMV-specific T cells (CMV-VST) to treat cytomegalovirus (CMV) infections is generally safe. Studies have found that these treatments have few side effects. Patients who received CMV-VSTs in various situations experienced minimal side effects, indicating that the treatment is well-tolerated.

In some studies, CMV-VSTs successfully treated patients with hard-to-treat CMV infections. Most patients responded well, and the treatment proved effective and safe. This suggests a low risk of serious side effects, based on the available data.

For those considering joining a trial involving CMV-VSTs, this information indicates that the treatment has a good safety record according to previous research. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike standard treatments for cytomegalovirus (CMV) infections, such as antiviral medications that work to inhibit virus replication, CMV-specific T cells (CMV-VST) offer a unique approach by harnessing the body’s immune system. This treatment uses donor-derived T lymphocytes specifically reactive to CMV peptides, which means it targets the virus more directly and could provide a more precise immune response. Researchers are excited about CMV-VST because it has the potential to offer a targeted, immune-based solution that may be effective even when traditional antivirals are not, and could reduce the risk of resistance developing.

What evidence suggests that CMV-VST might be an effective treatment for CMV infection?

Research has shown that special immune cells, called CMV-specific T cells, hold promise in treating cytomegalovirus (CMV) infections. In this trial, participants will receive CMV-specific donor-derived T lymphocytes (CMV-VST). Studies have found that these cells can help patients respond well to CMV. These T cells effectively reduce the occurrence of CMV, a serious issue for individuals with weakened immune systems. They have also demonstrated minimal side effects, suggesting a potentially safe option. Overall, CMV-specific T cells appear to be a promising way to manage CMV infections, particularly in patients with compromised immune systems. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for patients with a severe combined immunodeficiency who are struggling with CMV infection and pneumonia. Participants must have persistent viremia despite treatment, indicating a recalcitrant CMV infection.

Inclusion Criteria

Profound combined immunodeficiency

Viremia

I have pneumonia.

Exclusion Criteria

I am taking a steroid dose equal to or more than 0.5 mg/kg of prednisolone.

Administration of another investigational product

I am currently on immunotherapy and it's been less than 3 half-lives since my last dose.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Treatment of CMV using CMV-specific donor-derived T lymphocytes (CMV-VST) in a patient with profound combined immunodeficiency

Until discharge from inpatient unit

Twice a week

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Weekly for 3 months, monthly from 3-12 months, every 3 months till 2 years

Long-term follow-up

Survival status assessed every 6 months through year 15

13 years

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• CMV-VST

Trial Overview The study is testing the use of CMV-specific donor-derived T lymphocytes (CMV-VST) to treat stubborn CMV infections in patients whose immune systems are severely compromised.

How Is the Trial Designed?

Group I: CMV-specific donor-derived T lymphocytes (CMV-VST). Experimental Treatment 1 Intervention

Mixture of donor lymphocytes, reactive to peptides derived from cytomegalovirus.

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Alberta Health services

Collaborator

Trials

168

Recruited

658,000+

Alberta Precision Laboratories

Collaborator

University of Alberta

Collaborator

Trials

957

Recruited

437,000+

Citations

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

Virus-Specific T-Cell Therapy for Prophylaxis and Treatment of ... The CMV infection rate was 28% (interquartile range [IQR], 14%–44%) when CMV-VSTs were used as prophylaxis. Response rates for non–refractory ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11510890/

Use of Specific T Lymphocytes in Treating ... Currently, the best option for treating refractory or resistant CMV is maribavir, with a response rate of around 57% [41]. Therefore, although ...

3. 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, ...

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. haematologica.org haematologica.org/article/view/haematol.2022.280685

Cytomegalovirus-specific T cells restricted for shared and ... The emergence of circulating cytomegalovirus (CMV)- specific T cells correlates with protection from CMV reactivation, an important risk factor for non-relapse ...