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

49 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase II trial studies how well donor cytomegalovirus-specific cytotoxic T-lymphocytes work in treating patients with a cytomegalovirus infection that has come back or has not gotten better despite standard therapy. White blood cells from donors who have been exposed to cytomegalovirus may be effective in treating patients with a cytomegalovirus infection.

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 the treatment with CMV-specific T-cells generally safe for humans?

Research indicates that using CMV-specific T-cells in immunocompromised patients, such as those undergoing bone marrow or stem cell transplants, has been evaluated for safety. These studies suggest that the treatment is generally safe and helps in rebuilding the immune system to fight CMV infections. ^{1 2 3 4 5}

How does the treatment Allogeneic Cytomegalovirus-Specific Cytotoxic T lymphocytes differ from other treatments for Cytomegalovirus infection?

This treatment is unique because it involves using T-cells (a type of immune cell) from a donor that are specifically trained to target and fight the Cytomegalovirus, rather than relying on antiviral drugs. This approach aims to restore the patient's immune response to the virus, which is particularly beneficial for those who have weakened immune systems, such as after a stem cell transplant. ^{1 3 6 7 8}

What data supports the effectiveness of the treatment Allogeneic Cytomegalovirus-Specific Cytotoxic T lymphocytes for Cytomegalovirus Infection?

Research shows that using CMV-specific T cells from donors can help rebuild the immune system in patients who have had stem cell transplants, protecting them from CMV disease. This approach has been effective in treating CMV reactivation in patients with weakened immune systems. ^{1 2 3 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

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]

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]

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]

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 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]

Citations

1. England 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. [2013]

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

CMV-specific T cell therapy. [2007]

3. Denmark 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. [2014]

4. Korea (South) pubmed.ncbi.nlm.nih.gov

Adoptive immunotherapy for cytomegalovirus (CMV) disease in immunocompromised patients. [2005]

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

Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor. [2023]

6. United States 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. [2006]

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

Status of Cytomegalovirus Prevention and Treatment in 2000. [2019]

8. United States 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. [2006]