CMV-Specific T-Cells for Cytomegalovirus Infection

Overseen By Betul Oran

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Antivirals

Must not be taking: Steroids, ATG

Disqualifiers: Uncontrolled infections, Active acute GVHD, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 4-6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment using special immune cells from donors to combat cytomegalovirus (CMV) infections that have not improved with standard antiviral treatments. The focus is on using these donor cells, known as allogeneic cytomegalovirus-specific cytotoxic T-lymphocytes, to target the virus directly. Suitable candidates for this trial include those with ongoing CMV infections despite standard antiviral drugs or those who cannot tolerate these drugs due to side effects. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that patients must be able to taper steroids to 0.5 mg/kg/day of prednisone or less. If you are on high doses of prednisone or certain other treatments, you may need to adjust your medication.

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

Research shows that using special immune cells from donors, called CMV-specific T-cells, is generally safe. These cells have been used in studies to treat CMV infections that don't respond to other treatments. The results indicate that this method is both effective and well-tolerated.

One study found this treatment to be a safe option for people with difficult CMV infections after stem cell transplants. Another study showed that most patients did not experience serious side effects, with only a few having minor issues. Importantly, a review of several studies revealed that deaths related to CMV infection were rare with this treatment. Out of many studies, only two reported a small number of deaths, suggesting that the treatment is quite safe overall.

These findings support the idea that CMV-specific T-cells can be a reliable option for those dealing with persistent CMV infections. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard antiviral drugs used for cytomegalovirus (CMV) infection, which primarily aim to suppress the virus's replication, allogeneic cytomegalovirus-specific cytotoxic T-lymphocytes offer a novel approach by harnessing the power of the immune system. These engineered T-cells are designed to specifically target and destroy CMV-infected cells, potentially leading to a more precise and effective treatment. Researchers are excited about this treatment because it could provide a more sustainable immune response, reducing the need for ongoing antiviral medications and potentially improving outcomes for patients who have limited options with current therapies.

What evidence suggests that this treatment might be an effective treatment for cytomegalovirus infection?

Studies have shown that donor cytomegalovirus-specific cytotoxic T-lymphocytes, special white blood cells, can effectively treat CMV infections unresponsive to standard treatments. This trial will evaluate the use of allogeneic CMV-specific cytotoxic T-lymphocytes. Research indicates that these special T-cells are a safe option for people with hard-to-treat CMV infections. In some studies, most patients who received this treatment improved without any infection-related deaths. This treatment offers hope for those dealing with persistent CMV problems. ^{2 3 4 5 6}

Who Is on the Research Team?

Betul Oran, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with persistent or recurrent cytomegalovirus (CMV) infection despite standard therapy, including those who can't tolerate such treatments due to side effects. Eligible participants may have blood cancers, tumors, or be immunocompromised. They must not have acute graft-versus-host disease grades II-IV or other uncontrolled infections.

Inclusion Criteria

Written informed consent and/or signed assent line from patient, parent or guardian

Negative pregnancy test in female patients of childbearing potential

I may have cancer, had a stem cell transplant, or have a weak immune system with CMV infection.

Exclusion Criteria

I do not have any uncontrolled infections and am not currently fighting a viral infection.

My cancer is currently growing or spreading and is not under control.

I am not taking more than a low dose of prednisone and haven't had certain immune treatments in the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive allogeneic cytomegalovirus-specific cytotoxic T-lymphocytes intravenously. Patients with partial response, stable disease, or progressive disease may receive an additional dose at a minimum of 2 weeks from the first infusion.

4-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments for graft-versus-host disease and overall survival.

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Allogeneic Cytomegalovirus-Specific Cytotoxic T lymphocytes

Trial Overview The trial tests whether white blood cells from donors previously exposed to CMV can effectively treat patients with CMV infections that haven't improved after standard antiviral therapies like ganciclovir and foscarnet.

How Is the Trial Designed?

Group I: Treatment (allogeneic CMV-specific cytotoxic T-lymphocytes) Experimental Treatment 1 Intervention

Patients receive allogeneic cytomegalovirus-specific cytotoxic T-lymphocytes IV. Patients with partial response, stable disease, or progressive disease may receive an additional dose of allogeneic cytomegalovirus-specific cytotoxic T-lymphocytes at a minimum of 2 weeks from the first infusion.

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

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]

In a study of 18 patients after allogeneic hematopoietic stem cell transplantation, real-time polymerase chain reaction (RT-PCR) was found to be the most sensitive method for detecting CMV-specific T cells, identifying responses in 88% of cases when using a combination of pp65-peptide and pp65-protein for stimulation.

The use of pp65-protein for T-cell activation allows for detection of CMV-specific T cells without HLA restriction, enhancing the ability to monitor immune reconstitution and potentially guiding treatment strategies to prevent active CMV disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid monitoring of immune reconstitution after allogeneic stem cell transplantation--a comparison of different assays for the detection of cytomegalovirus-specific T cells. Abu-Khader, A., Krause, S.[2013]

In a study of 3 CMV-seropositive patients who received stem cell transplants from CMV-seronegative donors, researchers found that CMV-specific CD8(+) T cells (CMV-CTLs) were predominantly mature effector cells, indicating a strong immune response post-transplant.

The study revealed that CMV-CTL clones persisted differently based on CMV reactivation; in one case without reactivation, recipient-derived CMV-CTLs dominated, while in cases with reactivation, the dominant clones were derived from the donor, highlighting the importance of donor-derived immunity in managing CMV after transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Persistence of recipient-derived as well as donor-derived clones of cytomegalovirus pp65-specific cytotoxic T cells long after allogeneic hematopoietic stem cell transplantation. Terasako-Saito, K., Nakasone, H., Tanaka, Y., et al.[2014]

In a study of 20 renal transplant recipients, CMV-specific cytotoxic T lymphocytes (CTLs) were found to limit the viral load of cytomegalovirus (CMV) as indicated by lower levels of antigenemia, suggesting their protective role against CMV disease.

The presence of CMV-specific CTLs was inversely correlated with high levels of antigenemia and the development of CMV disease, indicating that stronger CTL responses may help prevent severe CMV infections post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytomegalovirus (CMV)-specific T cell immunity after renal transplantation mediates protection from CMV disease by limiting the systemic virus load. Reusser, P., Cathomas, G., Attenhofer, R., et al.[2006]

An innovative in vitro system was developed to generate human cytomegalovirus (CMV)-specific cytotoxic T cells (CTL) using autologous donor leucocytes coated with CMV antigens, effectively producing CTLs from seropositive donors.

The study demonstrated that CMV-specific CTLs could be inhibited by monoclonal antibodies targeting CMV-related proteins, indicating a potential mechanism for regulating CTL activity in therapeutic settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Definition of human cytomegalovirus-specific target antigens recognized by cytotoxic T cells generated in vitro by using an autologous lymphocyte system. Charpentier, B., Michelson, S., Martin, B.[2006]

CMV infection is a major risk after allogeneic stem cell transplantation, but reconstituting CMV-specific T cell responses can help protect patients from developing CMV disease.

Two strategies to enhance T cell immunity against CMV include transferring selected CMV-specific T cells directly from the donor to the patient and expanding these T cells in vitro using antigen presenting cells, both of which aim to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CMV-specific T cell therapy. Einsele, H., Kapp, M., Grigoleit, GU.[2007]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0006497123114728

Adoptive Therapy with Cytomegalovirus-Specific Cytotoxic ... The rates of refractory CMV infection are reported in allo-HSCT recipients ranging from 19.0% to 50.6%. Patients with refractory CMV infection ...

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

Use of Specific T Lymphocytes in Treating ... Adoptive hCMV-specific T-cell immunotherapy appears to be a safe, effective alternative for refractory CMV-CS in HCT.

3. nature.com nature.com/articles/s41409-021-01499-0

specific cytotoxic T lymphocyte therapy resolve CMV ... Early intervention with CMV-CTLs combined with standard antiviral treatment can facilitate immune recovery, resolve CMV diseases, and prevent ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02210078

Donor Cytomegalovirus-Specific Cytotoxic T-Lymphocytes ... White blood cells from donors who have been exposed to cytomegalovirus may be effective in treating patients with a cytomegalovirus infection. Detailed ...

5. 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 ... Mortality due to CMV infection was reported in 19 studies with most of the studies reporting no deaths, and 2 studies reporting a total of 3 ...

6. clinicaltrials.gov clinicaltrials.gov/show/NCT00673868

Cytomegalovirus (CMV) Specific Cytotoxic T Lymphocytes ... This study examines the immunologic and virologic effects of prophylactic CMV specific CTL in recipients of T cell depleted stem cell transplant (TCD SCT) at ...