CMV Vaccine for Bone Marrow Transplant Recipients

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: City of Hope Medical Center

Must not be taking: Antivirals, Live vaccines

Disqualifiers: Cord blood transplant, Autoimmune conditions, 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: 2

Duration: 8 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the best dose and assess the side effects of a new vaccine designed to help patients resist complications from cytomegalovirus (CMV), a virus that can be dangerous after a stem cell transplant. The Multi-peptide CMV-Modified Vaccinia Ankara Vaccine introduces small parts of the CMV virus to help the immune system recognize and combat it. The trial seeks children undergoing stem cell transplants who have had CMV before and have not received certain CMV therapies in the last six months. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking medical advancements.

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 medications like antiviral drugs for CMV and some immunosuppressive therapies are not allowed. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the CMV-Modified Vaccinia Ankara Vaccine is generally safe for people. In earlier studies, participants tolerated the vaccine well, with only mild side effects reported. For instance, some experienced minor reactions at the injection site, such as redness or swelling, while a few had mild fever or tiredness. Importantly, these studies found no serious side effects linked to the vaccine. This suggests that the vaccine is safe and may help strengthen the body's defense against CMV, especially for those undergoing stem cell transplants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

The multi-peptide CMV-Modified Vaccinia Ankara Vaccine is unique because it uses a novel approach to prevent cytomegalovirus (CMV) infections in bone marrow transplant recipients. Unlike standard antiviral drugs, which target the virus after it has already caused problems, this vaccine primes the immune system to recognize and fight CMV before it can establish an infection. Researchers are excited because the vaccine could offer a proactive and potentially more effective way to protect vulnerable patients, reducing the risk of CMV complications and improving overall outcomes. Plus, by using a multi-antigen approach, the vaccine aims to offer broader and more robust protection compared to treatments that focus on a single viral component.

What evidence suggests that the Multi-peptide CMV-Modified Vaccinia Ankara Vaccine might be an effective treatment for CMV in bone marrow transplant recipients?

Research has shown that the CMV-Modified Vaccinia Ankara Vaccine may help bone marrow transplant patients combat CMV (cytomegalovirus) infections. This vaccine boosts the immune system by increasing the number of T-cells targeting CMV. In studies, vaccinated patients had more of these protective T-cells than those who did not receive the vaccine. This trial will assess the vaccine's effectiveness in reducing CMV-related issues in transplant patients. Although further research is necessary, these early results offer promise for preventing CMV infections in this vulnerable group. ^{1 3 6 7 8}

Who Is on the Research Team?

Anna Pawlowska, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for pediatric patients with cytomegalovirus (CMV) who are about to receive a donor stem cell transplant. They must be HIV, HCV negative and HBV DNA negative if previously exposed. Participants need to agree to use contraception and follow the study for one year post-transplant. It's not open to those on recent anti-CMV therapy, with congenital immune deficiencies, active autoimmune conditions needing immunosuppression (except aplastic anemia), or unable to comply with study procedures.

Inclusion Criteria

Participant must be willing to comply with study and/or follow-up procedures, including willingness to be followed for one year post-HCT

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

I am scheduled for a stem cell transplant with a closely matched donor and without T-cell removal.

Exclusion Criteria

I am not taking any medications that could affect the study drug's evaluation.

I haven't taken immunosuppressants for an autoimmune condition in the last 5 years, except if I have aplastic anemia.

I am scheduled for a cord blood transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multi-antigen CMV-modified vaccinia ankara vaccine intramuscularly on days 28 and 56 post-HCT

8 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year post-HCT

What Are the Treatments Tested in This Trial?

Interventions

• Multi-peptide CMV-Modified Vaccinia Ankara Vaccine

Trial Overview The trial is testing a multi-antigen CMV-modified vaccinia ankara vaccine in children undergoing stem cell transplants. The aim is to find the safest dose that works best at helping these young patients resist life-threatening complications from CMV after their transplant.

How Is the Trial Designed?

Group I: Supportive Care (multi-antigen CMV-modified vaccinia ankara) Experimental Treatment 2 Interventions

Patients receive multi-antigen CMV-modified vaccinia ankara vaccine IM on days 28 and 56 post-HCT.

Multi-peptide CMV-Modified Vaccinia Ankara Vaccine is already approved in United States, European Union for the following indications:

Approved in United States as Triplex Vaccine for:

• Prevention of clinically significant CMV viremia in transplant recipients

Approved in European Union as Triplex Vaccine for:

• Prevention of clinically significant CMV viremia in transplant recipients

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

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 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]

In a phase 2 trial involving 102 high-risk CMV-seropositive hematopoietic stem cell transplant recipients, the Triplex vaccine showed a trend towards reducing CMV reactivation, with 9.8% of Triplex recipients experiencing reactivation compared to 19.6% in the placebo group.

The Triplex vaccine was found to be safe, with no serious adverse events or deaths related to the vaccine, and it successfully increased levels of CMV-specific T cells, suggesting it effectively enhances the immune response against CMV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poxvirus Vectored Cytomegalovirus Vaccine to Prevent Cytomegalovirus Viremia in Transplant Recipients: A Phase 2, Randomized Clinical Trial. Aldoss, I., La Rosa, C., Baden, LR., et al.[2023]

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]

The CMVpp65 peptide vaccination was well tolerated in 10 patients after allogeneic stem cell transplantation, with 7 out of 9 patients clearing CMVpp65 antigenemia after four vaccinations, indicating its potential efficacy in preventing CMV reactivation.

The vaccination led to significant increases in CMV-specific CD8+ T cells and neutralizing antibodies, suggesting that both cellular and humoral immune responses are important for the clearance of CMV, making it a promising strategy for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peptide vaccination in the presence of adjuvants in patients after hematopoietic stem cell transplantation with CD4+ T cell reconstitution elicits consistent CD8+ T cell responses. Schmitt, M., Schmitt, A., Wiesneth, M., et al.[2018]

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 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]

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 ... Giving the CMV-MVA triplex vaccine to donors may help prevent CMV infection of patients undergoing stem cell transplantation. Detailed Description. PRIMARY ...

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

Cytomegalovirus Triplex vaccine in pediatric hematopoietic ... High levels of functional CMV-specific T-cell response were measured in patients treated at both Triplex DL, in both age groups, in transplant recipients with ...

4. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/multi-peptide-cmv-modified-vaccinia-ankara-vaccine?pn=1

Clinical Trials Using Multi-peptide CMV-Modified Vaccinia ... Review the clinical trials studying multi-peptide cmv-modified vaccinia ankara vaccine on this list and use the filters to refine the results by age and ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10294297/

Hematopoietic stem cell donor vaccination with CMV Triplex ... Triplex is a viral vectored recombinant vaccine expressing three immunodominant CMV antigens. The vector is modified vaccinia Ankara (MVA), an attenuated, non- ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06059391

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) ...

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

Highly stable and immunogenic CMV T cell vaccine ... We developed a new generation Triplex vaccine candidate, T10-F10, with different sequence modifications for enhanced vaccine stability.

8. 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.