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

Trial Summary

What is the purpose of this trial?

This phase II clinical trial tests how well the cytomegalovirus-modified vaccinica Ankara (CMV-MVA) Triplex vaccine given to human leukocyte antigens (HLA) matched related stem cell donors works to prevent cytomegalovirus (CMV) infection in patients undergoing hematopoietic stem cell transplant. The CMV-MVA Triplex vaccine works by causing an immune response in the donors body to the CMV virus, creating immunity to it. The donor then passes that immunity on to the patient upon receiving the stem cell transplant. Giving the CMV-MVA triplex vaccine to donors may help prevent CMV infection of patients undergoing stem cell transplantation.

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.

What data supports the effectiveness of the CMV-MVA Triplex Vaccine treatment for blood cancers?

Research shows that the CMV-MVA Triplex Vaccine safely induces strong and long-lasting immune responses against cytomegalovirus (CMV) in healthy adults, which suggests it could be effective in boosting the immune system in patients with blood cancers. The vaccine uses a modified virus to stimulate the body's T-cells (a type of immune cell) to fight CMV, and similar approaches have shown promise in cancer immunotherapy. ^{1 2 3 4 5}

Is the CMV-MVA Triplex Vaccine safe for humans?

The CMV-MVA Triplex Vaccine has been tested in healthy adults and was found to be safe, with no serious side effects related to the vaccine. Any mild reactions, like pain at the injection site, were temporary and resolved on their own. ^{1 2 3 4 6}

What makes the CMV-MVA Triplex Vaccine treatment unique for blood cancers?

The CMV-MVA Triplex Vaccine is unique because it uses a modified vaccinia Ankara (MVA) virus to safely stimulate a strong and lasting immune response specifically against cytomegalovirus (CMV) antigens, which is particularly beneficial for patients with blood cancers who have weakened immune systems. This approach is novel as it targets CMV-specific T-cells, enhancing the body's ability to fight infections without causing serious side effects. ^{1 2 3 4 5}

Research Team

Vaibhav Agrawal

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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]

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]

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]

References

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

MVA vaccine encoding CMV antigens safely induces durable expansion of CMV-specific T cells in healthy adults. [2021]

2. United States 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. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Uptake of antigens from modified vaccinia Ankara virus-infected leukocytes enhances the immunostimulatory capacity of dendritic cells. [2020]

4. United States 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. [2020]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Armored modified vaccinia Ankara in cancer immunotherapy. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of IMVAMUNE, a promising candidate as a third generation smallpox vaccine. [2006]