CMV-MVA Triplex Vaccine for Blood Cancers

Recruiting at 2 trial locations

Overseen By Vaibhav Agrawal, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: Antivirals, Alemtuzumab, Vaccines, others

Disqualifiers: Autoimmune disease, Prior transplant, others

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

Compensation: Varies

Number of Visits: 14

216 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a new vaccine, the CMV-MVA Triplex, in preventing infections from the common virus CMV in patients undergoing stem cell transplants for blood cancers such as leukemia or lymphoma. The vaccine is administered to stem cell donors to boost their immune response to CMV, which is then transferred to patients during the transplant. The trial compares the vaccine to a placebo to assess its effectiveness. Suitable candidates include those planning to receive a stem cell transplant for specific blood cancers and who have previously tested positive for CMV. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but certain antiviral medications for CMV and other investigational drugs 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 shows that the CMV-MVA Triplex vaccine is generally safe for people. One study found the vaccine to be well-tolerated and effective in boosting the body's defense against cytomegalovirus (CMV), helping the body fight the virus without causing serious side effects. Another study demonstrated that the vaccine safely increased the number of specific immune cells targeting CMV, which is crucial for controlling the virus.

In studies with children, the vaccine was also tested for safety and showed positive results, indicating it didn't cause harmful effects in children at high risk for CMV problems. These findings suggest that the CMV-MVA Triplex vaccine is safe for both adults and children. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for blood cancers, which often involve chemotherapy and radiation, the CMV-MVA Triplex Vaccine is designed to harness the body's immune system. Researchers are excited about this vaccine because it specifically targets cytomegalovirus (CMV), a common infection that can cause severe complications in patients undergoing stem cell transplants. The vaccine works by stimulating the immune system to better fight CMV, potentially reducing the risk of infection and improving transplant outcomes. This approach is particularly promising because it could enhance the quality of life for patients by preventing infections without the need for additional drugs that might have more side effects.

What evidence suggests that the CMV-MVA Triplex Vaccine could be effective for preventing CMV infection in blood cancer patients?

Research shows that the CMV-MVA Triplex vaccine, which participants in this trial may receive, may help prevent cytomegalovirus (CMV) infections. Studies have found that this vaccine can safely strengthen the body's immune system by increasing specific cells that fight CMV. Earlier research demonstrated that the vaccine effectively created a strong immune response, suggesting it might help control the virus in the blood. By boosting the immune system in this way, patients undergoing stem cell transplants may gain better protection from CMV-related issues. ^{1 2 4 5 6}

Who Is on the Research Team?

Vaibhav Agrawal

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for adult patients with certain blood cancers undergoing stem cell transplants and their HLA-matched related donors. Patients must have a good performance status, proper organ function, and agree to birth control post-transplant. Excluded are those with prior transplants, severe health conditions, or on conflicting treatments.

Inclusion Criteria

You have tested positive for CMV antibodies.

Consent will be obtained in accordance with institutional regulations.

I can take care of myself and perform daily activities.

Exclusion Criteria

DONORS: Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

RECIPIENTS: Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures

RECIPIENTS: Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccination and Stem Cell Mobilization

Donors receive Triplex vaccine or placebo and undergo stem cell mobilization with G-CSF, followed by apheresis for peripheral blood stem cell collection

14 days

Multiple visits for vaccination and stem cell collection

Transplantation

Recipients undergo pre-transplant conditioning and hematopoietic stem cell transplantation

Up to 9 weeks post-donor vaccination

In-patient stay for transplantation

Follow-up

Participants are monitored for safety and effectiveness after transplantation, including CMV events and immune response

1 year

Follow-up visits on days 14, 28, 42, 56, 70, 100, 140, 180, 270, and 365 post-transplantation

What Are the Treatments Tested in This Trial?

Interventions

• CMV-MVA Triplex Vaccine

Trial Overview

The study tests if the CMV-MVA Triplex vaccine given to stem cell donors can prevent CMV infection in transplant recipients. It's a phase II trial where the donor's immune response to CMV is hoped to be transferred to the patient through transplantation.

How Is the Trial Designed?

Group I: Arm I (Triplex vaccination) Experimental Treatment 7 Interventions

DONORS: Donors receive Triplex vaccine IM on day 0 and then undergo stem cell mobilization with G-CSF on days 5 to 9 and apheresis for peripheral blood stem cell collection on days 10 to 14 per standard of care. Donors may optionally undergo blood sample collection on study. RECIPIENTS: Recipients undergo pre-transplant conditioning on days -60 to 0 and undergo HCT with the donor peripheral blood stem cells within 9 weeks of donor vaccination on day 0. Recipients undergo blood sample collection on study.

Group II: Arm II (Placebo) Placebo Group 7 Interventions

DONORS: Donors receive placebo IM on day 0 and undergo stem cell mobilization with G-CSF on days 5 to 9 and apheresis for peripheral blood stem cell collection on days 10 to 14 per standard of care. Donors may optionally undergo blood sample collection on study. RECIPIENTS: Recipients undergo pre-transplant conditioning on days -60 to 0 and undergo HCT with the donor peripheral blood stem cells within 9 weeks of donor vaccination on day 0. Recipients undergo blood sample collection on study.

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

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]

The modified vaccinia Ankara (MVA) vaccine encoding the carcinoembryonic antigen (CEA) and costimulatory molecules induced strong CD4+ and CD8+ T-cell responses in mice, demonstrating its potential as an effective cancer vaccine.

A diversified vaccination regimen using MVA-CEA/TRICOM as a prime followed by rF-CEA/TRICOM as a boost resulted in significantly better antitumor responses and increased survival compared to traditional regimens, highlighting the efficacy of this approach in enhancing immune responses against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified vaccinia virus ankara recombinants are as potent as vaccinia recombinants in diversified prime and boost vaccine regimens to elicit therapeutic antitumor responses. Hodge, JW., Poole, DJ., Aarts, WM., 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]

The Phase I trial of the MVA-BN smallpox vaccine involved 86 healthy subjects and demonstrated that all participants in the highest dose group (10^8 TCID50) successfully developed an immune response (seroconversion).

The vaccine was well tolerated, with only mild to moderate injection site pain reported, suggesting that MVA-BN could be a safe and effective alternative to traditional smallpox vaccines, especially for individuals who cannot receive those vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of IMVAMUNE, a promising candidate as a third generation smallpox vaccine. Vollmar, J., Arndtz, N., Eckl, KM., et al.[2006]

Modified vaccinia Ankara (MVA) is a promising cancer vaccine platform that effectively stimulates both innate and adaptive immune responses, leading to strong and lasting immunity against tumors.

MVA has a strong safety profile due to its inability to replicate in human cells, making it a suitable option for cancer immunotherapy while minimizing the risk of adverse immune reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Armored modified vaccinia Ankara in cancer immunotherapy. Atay, C., Medina-Echeverz, J., Hochrein, H., et al.[2023]

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]

Citations

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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 ...

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A Vaccine (CMV-MVA Triplex Vaccine) for the ...

This phase Ib trial tests the safety, side effects, and how well cytomegalovirus (CMV)-modified vaccinia Ankara (MVA) Triplex vaccine works in enhancing ...

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NCT06059391 | CMV-MVA Triplex Vaccination in HLA ...

This phase II clinical trial tests how well the cytomegalovirus-modified vaccinica Ankara (CMV-MVA) Triplex vaccine given to human leukocyte antigens (HLA) ...

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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.

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cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-06837

CMV-MVA Triplex Vaccination in HLA-Matched Related ...

This phase II clinical trial tests how well the cytomegalovirus-modified vaccinica Ankara (CMV-MVA) Triplex vaccine given to human leukocyte antigens (HLA) ...

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

Cytomegalovirus Triplex vaccine in pediatric hematopoietic ...

Triplex vaccine in pediatric hematopoietic stem cell transplant patients at high risk for cytomegalovirus complications: evaluation of vaccine safety, ...