CMV-MVA Triplex Vaccine for Cancer

Not yet recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

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

Disqualifiers: Autoimmune conditions, Poor risk disease, others

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

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a vaccine designed to boost the immune system against CMV, a common virus, in individuals receiving stem cell transplants from partially matched donors. It targets patients at higher risk of CMV infections, which can cause serious complications after a transplant. The trial seeks to determine if the vaccine is safe and effective in preventing CMV-related issues. Individuals with a planned stem cell transplant for certain blood cancers or disorders who are CMV-positive might be suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this potentially groundbreaking vaccine.

Will I have to stop taking my current medications?

The trial requires that certain medications be stopped from the time of the stem cell transplant to 70 days after. These include live vaccines, some antiviral medications, and certain immunosuppressive therapies. It's best to discuss your specific medications with the trial team to see if they are affected.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the CMV-MVA Triplex vaccine is generally safe. Studies have found no serious side effects or major health issues linked to the vaccine. Some participants have experienced common reactions, such as mild soreness at the injection site and temporary tiredness, which are not serious.

The vaccine has been tested in both healthy individuals and those with weakened immune systems, and it is well-tolerated by both groups. This includes people who have undergone stem cell transplants, which is crucial since this trial focuses on preventing CMV infection after such procedures.

In summary, evidence suggests that the CMV-MVA Triplex vaccine is safe and may help boost immunity against CMV, particularly for those at higher risk of infection, such as stem cell transplant patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the CMV-MVA Triplex Vaccine because it takes a novel approach to boosting the immune system in cancer patients undergoing hematopoietic cell transplantation (HCT). Unlike current antiviral drugs like ganciclovir or acyclovir that primarily work by directly inhibiting viral replication, this vaccine aims to enhance the body's immune response against cytomegalovirus (CMV) infections, which are common and potentially severe in these patients. The vaccine is used alongside letermovir, an antiviral that prevents CMV from replicating, which represents a synergistic method to protect patients from CMV-related complications. This combination could offer a more robust and comprehensive defense against CMV, potentially improving outcomes for patients undergoing HCT.

What evidence suggests that the CMV-MVA Triplex vaccine could be effective in preventing CMV viremia in patients undergoing haploHCT?

Research has shown that the CMV-MVA Triplex vaccine strengthens the body's defense against CMV, a virus that can cause serious problems after a stem cell transplant. This trial will evaluate the vaccine in different contexts:

- In one arm, donors will receive the CMV-MVA Triplex vaccine along with G-CSF.

- In another arm, recipients will receive the CMV-MVA Triplex vaccine and letermovir, with variations in the duration of letermovir administration across different modalities.

- Another arm will focus on recipients receiving only the CMV-MVA Triplex vaccine.

The vaccine has proven safe and effective for both healthy individuals and those with weakened immune systems. Studies have shown that it reduces the risk of CMV infection by triggering strong and lasting immune responses. In earlier trials, it successfully lowered CMV levels in patients who had stem cell transplants. These findings suggest that the vaccine could help prevent CMV-related issues in patients undergoing certain types of stem cell transplants. ^{1 3 6 7 8}

Who Is on the Research Team?

Ryotaro Nakamura

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with various blood cancers undergoing a haploidentical hematopoietic stem cell transplant, who need protection against CMV infections. Participants should not have received certain antiviral drugs recently and must be able to understand the study requirements.

Inclusion Criteria

DONORS: Agreement by females and males of childbearing potential to use an effective method of birth control (hormonal or barrier method) or abstain from heterosexual activity prior to study entry and for up to 90 days post-vaccination.

I am scheduled for a stem cell or bone marrow transplant for blood cancer treatment.

My donor is a half-match and may have specific HLA mismatches.

Exclusion Criteria

RECIPIENTS: Specific medical history or conditions that are deemed high risk for the study.

RECIPIENTS: Various medical and health conditions that preclude participation in the study.

RECIPIENTS: Prospective participants who may have difficulties complying with study procedures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning and Transplantation

Patients receive myeloablative conditioning and undergo hematopoietic stem cell transplant from haploidentical vaccinated donor

0-4 weeks

Vaccination and Treatment

Patients receive CMV-MVA Triplex vaccine on days 28, 56, and 100, and letermovir treatment as per modality assignment

14 weeks

Multiple visits for vaccination and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 365 days post-HCT

Every 2 weeks until day 180, then at day 365

What Are the Treatments Tested in This Trial?

Interventions

• CMV-MVA Triplex Vaccine

Trial Overview The trial tests a vaccine called CMV-MVA Triplex designed to boost immunity against cytomegalovirus (CMV) in patients receiving stem cell transplants from partially matched donors. It aims to see if the vaccine is safe and can prevent CMV-related complications post-transplant.

How Is the Trial Designed?

Group I: Recipients, Modality 3 (CMV-MVA Triplex vaccine) Experimental Treatment 5 Interventions

Patients receive myeloablative conditioning during screening and undergo HCT from haploidentical vaccinated donor on day 0. Patients receive CMV-MVA Triplex vaccine IM QD on days 28, 56 and 100. Treatment continues in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection throughout the study.

Group II: Recipients, Modality 2 (CMV-MVA Triplex vaccine, letermovir) Experimental Treatment 6 Interventions

Patients receive myeloablative conditioning during screening and undergo HCT from haploidentical vaccinated donor on day 0. Patients receive CMV-MVA Triplex vaccine IM QD on days 28, 56 and 100 and receive letermovir IV over 1 hour or PO QD on days 7 to 28. Treatment continues in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection throughout the study.

Group III: Recipients, Modality 1 (CMV-MVA Triplex vaccine, letermovir) Experimental Treatment 6 Interventions

Patients receive myeloablative conditioning during screening and undergo HCT from haploidentical vaccinated donor on day 0. Patients receive CMV-MVA Triplex vaccine IM QD on days 28, 56 and 100 and receive letermovir IV over 1 hour or PO QD on days 7 to 100. Treatment continues in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection throughout the study.

Group IV: Donors (CMV-MVA Triplex vaccine, G-CSF) Experimental Treatment 4 Interventions

Participants receive CMV-MVA Triplex vaccine IM once and then receive G-CSF on study. Additionally, participants undergo apheresis on study as well as blood sample collection on study and may optionally undergo blood sample collection during follow up.

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+

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

Cytomegalovirus Triplex vaccine in pediatric hematopoietic ... Triplex demonstrated tolerability and immunogenicity in healthy adults, autologous and allogeneic HCT recipients, in whom it reduced CMV viremia. Based on ...

3. 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 ...

4. withpower.com withpower.com/trial/phase-2-lymphoma-9-2023-faf01

CMV-MVA Triplex Vaccine 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 ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04060277

Triplex Vaccine in Preventing CMV Infection in Patients ... This phase II trial studies how well Triplex vaccine works in preventing cytomegalovirus (CMV) infection in patients undergoing a hematopoietic stem cell ...

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

MVA vaccine encoding CMV antigens safely induces ... Vaccinations at all DL were safe with no dose-limiting toxicities. No vaccine-related serious adverse events were documented. Local and systemic reactogenicity ...

7. helocyte.com helocyte.com/development-pipeline/triplex/

Triplex The study demonstrated that Triplex is both safe and highly immunogenic, inducing robust expansion of CD4+ and CD8+ T-cells specific for each immuno-dominant ...

8. ashpublications.org ashpublications.org/blood/article/126/23/3108/135386/Safety-Maximum-Tolerated-Dose-and-Immunogenicity

Safety, Maximum Tolerated Dose and Immunogenicity of CMV ... The safety and marked immunogenicity of CMV-MVA-Triplex in this Phase I trial, warrant testing of the vaccine in the HCT setting.