CMV-MVA Triplex Vaccine for Blood Cancers

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Antivirals, Alemtuzumab, Live vaccines

Disqualifiers: Autoimmune disease, Pregnancy, Others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a vaccine that might help prevent cytomegalovirus (CMV) in individuals with blood cancers undergoing a stem cell transplant. The CMV-MVA Triplex Vaccine is administered to stem cell donors to enhance the recipient's immunity against CMV, reducing the risk of CMV disease post-transplant. Suitable candidates for this trial include individuals with certain blood cancers, such as leukemia or lymphoma, who plan to undergo a stem cell transplant from a related donor and have tested positive for CMV. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this potentially groundbreaking vaccine.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but certain antiviral medications and investigational products are not allowed. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that the CMV-MVA Triplex Vaccine is likely to be safe for humans?

Research has shown that the CMV-MVA Triplex vaccine is generally safe for people. Studies have found that this vaccine, which helps the body fight cytomegalovirus, is well-tolerated in trials. Specifically, one study found that it safely increased the body's defense cells (T cells) that target this virus. This indicates that the vaccine can help control the virus without causing major health issues.

Overall, while some people may experience mild side effects, the vaccine's safety record appears strong based on current research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about the CMV-MVA Triplex Vaccine for blood cancers because it offers a novel approach to preventing cytomegalovirus (CMV) infections, which are common complications after hematopoietic cell transplantation. Unlike standard antiviral drugs that treat CMV by targeting the virus directly, this vaccine stimulates the immune system to recognize and fight CMV using a multi-peptide CMV-modified Vaccinia Ankara platform. This method could potentially enhance the body's defense without the side effects associated with traditional antiviral medications. Additionally, the vaccine can be administered to both recipients and donors, potentially improving outcomes by reducing CMV-related complications before and after transplantation.

What evidence suggests that the CMV-MVA Triplex Vaccine might be an effective treatment for preventing CMV viremia in blood cancer patients?

Research has shown that the CMV-MVA Triplex vaccine can strengthen the body's defense against cytomegalovirus (CMV). Earlier studies proved that this vaccine safely boosts T cell responses, crucial for fighting CMV. It was also found to be safe and may help control the virus in the blood of people with weakened immune systems. In this trial, some participants will receive the multi-peptide CMV-modified Vaccinia Ankara vaccine after undergoing hematopoietic cell transplantation, while donors will receive the vaccine before granulocyte colony stimulating factor mobilization. These findings suggest that the vaccine could effectively enhance immunity and reduce CMV-related problems in patients receiving stem cell transplants for blood cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Ryotaro Nakamura, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for blood cancer patients undergoing donor stem cell transplant and their donors. Donors must consent to vaccination at least 14 days before donation, while recipients should be CMV seropositive, aged 18-75, willing to follow study procedures for a year post-transplant, and free from HIV/HCV/active HBV. Pregnant women or those who might become pregnant must use effective contraception.

Inclusion Criteria

RECIPIENT: Willingness to comply with study and/or follow-up procedures, including willingness to be followed for one year post-HCT

RECIPIENT: CMV seropositive

RECIPIENT: Negative serum or urine beta-HCG test (female patient of childbearing potential only) within two weeks of registration

Exclusion Criteria

RECIPIENT: Allergy treatment with antigens injections

I will be taking specific medications from my transplant until day 70 after.

I have a sickle cell disease needing a transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccination

Donors receive multi-peptide CMV-modified vaccinia Ankara vaccine injection between days -60 and -10 prior to granulocyte colony stimulating factor mobilization

7 weeks

Transplantation

Participants undergo hematopoietic cell transplantation on day 0

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Multi-peptide CMV-Modified Vaccinia Ankara Vaccine

Trial Overview The trial tests if vaccinating stem cell donors with the CMV-MVA Triplex vaccine can prevent cytomegalovirus (CMV) viremia in blood cancer patients receiving these donated cells. The goal is to see if this approach boosts the recipient's immunity against CMV and lowers disease risk after transplant.

How Is the Trial Designed?

Group I: Receipient (multi-peptide CMV-modified vaccinia Ankara vaccine) Experimental Treatment 1 Intervention

Participants undergo hematopoietic cell transplantation on day 0 and receive multi-peptide CMV-modified Vaccinia Ankara vaccine injection on days 28 and 56.

Group II: Donor (multi-peptide CMV-modified vaccinia Ankara vaccine) Experimental Treatment 1 Intervention

Donors receive multi-peptide CMV-modified vaccinia Ankara vaccine injection between days -60 and -10 prior to granulocyte colony stimulating factor mobilization.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Modified vaccinia Ankara (MVA) effectively infects human immune cells, particularly monocytes and dendritic cells, leading to strong activation and a Th-1-polarizing cytokine response, which is crucial for immunotherapy applications.

The interaction between MVA-infected leukocytes and uninfected immature dendritic cells results in the complete maturation of dendritic cells, enhancing their ability to stimulate T cells, suggesting a promising strategy for vaccine development and immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Uptake of antigens from modified vaccinia Ankara virus-infected leukocytes enhances the immunostimulatory capacity of dendritic cells. Flechsig, C., Suezer, Y., Kapp, M., et al.[2020]

The Modified Vaccinia Ankara (MVA) vaccine demonstrated equivalent antibody responses across three different production lots in a phase III trial involving 4005 healthy adults, with a seroconversion rate of 99.8%.

The vaccine was well tolerated, with only 6.0% of MVA recipients reporting trial-related adverse events, and no significant safety concerns, particularly regarding cardiac health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of three consecutive production lots of the non replicating smallpox vaccine MVA: A randomised, double blind, placebo controlled phase III trial. Overton, ET., Lawrence, SJ., Wagner, E., et al.[2021]

In a phase 2 clinical trial involving 20 patients with lymphoma or myeloma, the Triplex vaccine significantly enhanced the reconstitution of adaptive natural killer (NK) cells and CMV-specific T cells after autologous hematopoietic cell transplantation (auto-HCT), particularly in CMV-seronegative patients.

The vaccine led to a notable increase in adaptive NK cells and CMV-specific T cells, suggesting a potential for improved immune response post-transplant, although further research is needed to assess the clinical benefits of these immune enhancements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CMV Triplex Vaccine to Enhance Adaptive NK and T-cell Reconstitution After Autologous Hematopoietic Cell Transplantation. Rashidi, A., La Rosa, C., Curtsinger, J., et al.[2023]

The developed CMV vaccine, based on modified vaccinia Ankara (MVA), successfully expresses three key CMV antigens and shows strong immunogenicity, stimulating both primary and memory immune responses in mouse models.

In human studies, the vaccine effectively activates existing CMV-specific CD4(+) and CD8(+) T cell responses in healthy CMV-positive individuals and patients shortly after hematopoietic cell transplant, indicating its potential for therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A fusion protein of HCMV IE1 exon4 and IE2 exon5 stimulates potent cellular immunity in an MVA vaccine vector. Wang, Z., Zhou, W., Srivastava, T., et al.[2022]

The CMVPepVax vaccine demonstrated safety in a phase 1b trial with 36 CMV-seropositive patients undergoing stem-cell transplantation, showing no adverse effects on transplant outcomes or unexpected serious adverse events.

Patients receiving the CMVPepVax vaccine had significantly better relapse-free survival compared to those under observation, suggesting potential clinical benefits that warrant further investigation in a phase 2 trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Viraemia, immunogenicity, and survival outcomes of cytomegalovirus chimeric epitope vaccine supplemented with PF03512676 (CMVPepVax) in allogeneic haemopoietic stem-cell transplantation: randomised phase 1b trial. Nakamura, R., La Rosa, C., Longmate, J., et al.[2022]

The Triplex vaccine, which uses a modified vaccinia Ankara (MVA) platform to target three key cytomegalovirus (CMV) antigens, was found to be safe in a clinical trial involving 24 healthy adults, with no serious adverse events reported and only mild, transient side effects.

The vaccine successfully induced strong and lasting CMV-specific T-cell responses, even in individuals without prior immunity to CMV, suggesting its potential effectiveness for broader populations, including patients undergoing hematopoietic stem cell transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MVA vaccine encoding CMV antigens safely induces durable expansion of CMV-specific T cells in healthy adults. La Rosa, C., Longmate, J., Martinez, J., et al.[2021]

Vaccinating healthy donors with the Triplex vaccine before hematopoietic cell transplant (HCT) significantly increased levels of CMV-specific T cells in recipients, indicating enhanced immune protection against cytomegalovirus (CMV).

The Triplex vaccine was well-tolerated with minimal adverse events, and the approach shows promise for reducing the need for antiviral prophylaxis, which can hinder the development of CMV-specific immunity post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematopoietic stem cell donor vaccination with cytomegalovirus triplex augments frequencies of functional and durable cytomegalovirus-specific T cells in the recipient: A novel strategy to limit antiviral prophylaxis. La Rosa, C., Aldoss, I., Park, Y., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02506933

NCT02506933 | Multi-antigen CMV-MVA Triplex Vaccine in ... This randomized phase II trial studies the safety and how well multi-peptide cytomegalovirus (CMV)-modified vaccinia Ankara (MVA) vaccine works in reducing ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06059391

NCT06059391 | CMV-MVA Triplex Vaccination in HLA ... PRIMARY OBJECTIVE: I. To determine whether multi-peptide CMV-modified vaccinia Ankara vaccine (Triplex) is safe and effective in protecting against CMV events ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5216266/

MVA vaccine encoding CMV antigens safely induces ... First in human trial of Triplex vaccine shows safety and expansion of durable CMV-specific T cells with potential for viremia control.

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-03633

A Vaccine (CMV-MVA Triplex Vaccine) for the ... Giving CMV-MVA triplex vaccine may be safe, tolerable and/or effective in enhancing cytomegalovirus (CMV)-specific immunity and preventing CMV viremia in ...

5. nature.com nature.com/articles/s41541-024-00859-3

Highly stable and immunogenic CMV T cell vaccine ... Triplex has been shown to be safe and to elicit potent antigen-specific T cell responses in healthy and immunocompromised individuals. It was ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11215362/

Cytomegalovirus Triplex vaccine in pediatric hematopoietic ... Triplex is a modified vaccinia Ankara (MVA) vectored vaccine which expresses three immunodominant CMV proteins; pp65, IE1-exon4, and IE2-exon5. It has been ...