PEP-CMV Vaccine for Pediatric Brain Tumor

Recruiting at 14 trial locations

Overseen By Kelsey H Troyer, PhD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Nationwide Children's Hospital

Must not be taking: Immunosuppressants, Tumor-directed therapy

Disqualifiers: Pregnancy, HIV, Active infection, others

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

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new vaccine called PEP-CMV to help the immune system combat certain brain tumors in children and young adults. Researchers aim to determine the vaccine's effectiveness for those with newly diagnosed high-grade glioma or diffuse intrinsic pontine glioma, as well as recurring medulloblastoma. The trial combines standard chemotherapy with the vaccine to assess whether it can enhance the immune response against the tumors. Patients diagnosed with these specific brain tumors who have completed some initial treatments might be suitable candidates for this trial. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important research.

Will I have to stop taking my current medications?

The trial requires that participants stop taking certain medications before enrolling. For example, you must stop myelosuppressive anticancer therapy 21 days before, immunotherapy 30 days before, and non-myelosuppressive anticancer agents 7 days before enrollment. If you are on dexamethasone, the dose must be reduced to 0.1 mg/Kg/day or less.

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

Research has shown that the PEP-CMV vaccine, which targets a specific protein linked to the CMV virus, appears promising in early safety studies. In a previous study, researchers tested this vaccine on individuals aged 3 to 35 years. The study found that the vaccine was generally well-tolerated. Some participants experienced minor side effects, such as redness at the injection site or mild flu-like symptoms. These reactions are common with many vaccines and usually resolve quickly.

The PEP-CMV vaccine is now undergoing testing in a Phase 2 trial. Researchers have already gathered some safety information from earlier studies. Phase 2 trials focus more on the vaccine's effectiveness while continuing to monitor its safety. Although more information is needed, current evidence suggests the vaccine is safe enough for testing in a larger group. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for pediatric brain tumors, which often includes surgery, radiation, and chemotherapy, the PEP-CMV Vaccine targets the immune system directly. This vaccine is designed to stimulate an immune response specifically against cytomegalovirus (CMV), which is often found in tumor cells, potentially allowing the body to attack the cancer more effectively. Researchers are excited because this approach could enhance the effectiveness of existing chemotherapy treatments and offer a more targeted and less invasive option by harnessing the body's own defenses. This makes the PEP-CMV Vaccine a promising new addition to the arsenal against pediatric brain tumors.

What evidence suggests that the PEP-CMV Vaccine might be an effective treatment for pediatric brain tumors?

Research has shown that the PEP-CMV vaccine targets a part of the CMV virus, which may play a role in some brain tumors. An earlier study found that the vaccine was well-tolerated and could trigger an immune response in patients who had already received extensive treatment. Specifically, 26.6% of these patients survived for at least 12 months. In the current trial, participants will receive the PEP-CMV vaccine alongside standard chemotherapy with temozolomide. The vaccine uses a man-made protein to help the immune system fight the tumor. This method is being tested as a new treatment for children with serious brain tumors, such as high-grade glioma, diffuse intrinsic pontine glioma, and recurring medulloblastoma. ^{1 2 3 4 6}

Who Is on the Research Team?

Maryam Fouladi, MD

Principal Investigator

Nationwide Children's Hospital

Daniel Landi, MD

Principal Investigator

Duke Cancer Center

Eric M Thompson, MD

Principal Investigator

Washington University - St. Louis Children's Hospital

Are You a Good Fit for This Trial?

This trial is for pediatric patients aged 3-25 with high-grade glioma (HGG), diffuse intrinsic pontine glioma (DIPG), or recurrent medulloblastoma. They must have a confirmed diagnosis, measurable disease on MRI, and stable neurological deficits if present. Prior radiotherapy is required unless they're under 4 years old.

Inclusion Criteria

Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control

Patients with recurrent/progressive medulloblastoma (stratum I) must be willing to use a Pillsy medication event monitoring system

Patients' performance status must meet specified criteria

Exclusion Criteria

I do not have any known immunosuppressive diseases.

Pregnant or breast-feeding women are excluded

I am not taking more than 4 mg/day of dexamethasone.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Cycle

Participants receive one course of temozolomide for 5 days and the PEP-CMV vaccine on Days 21, 35, and 49

11 weeks

3 visits (in-person)

Subsequent Cycles

Participants receive the PEP-CMV vaccine every 28 days for up to 24 cycles

24 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 months

What Are the Treatments Tested in This Trial?

Interventions

• PEP-CMV Vaccine

Trial Overview The study tests PEP-CMV vaccine targeting CMV antigens in children with brain tumors like HGG, DIPG, and recurrent medulloblastoma. It explores the potential of this novel immunotherapy approach combined with Temozolomide chemotherapy and Tetanus Diphtheria Vaccine.

How Is the Trial Designed?

Group I: PEP-CMV Experimental Treatment 3 Interventions

Participants will receive standard chemotherapy with temozolomide for five days, followed by the study vaccine, PEP-CMV, on day 21. Participants will receive a tetanus diphtheria (Td) booster vaccine and a small dose Td preconditioning vaccine to prepare their immune system to receive their first PEP-CMV vaccine. Participants will receive the first 3 PEP-CMV vaccines every 2 weeks, and after the third vaccine, the rest of the vaccines will be given monthly. The first cycle is 77 days and all subsequent cycles are 28 days. The PEP-CMV vaccine may be received for up to 24 cycles.

PEP-CMV Vaccine is already approved in United States for the following indications:

Approved in United States as PEP-CMV Vaccine for:

• High Grade Glioma
• Diffuse Intrinsic Pontine Glioma
• Recurrent Medulloblastoma

Who Is Running the Clinical Trial?

Nationwide Children's Hospital

Lead Sponsor

Trials

354

Recruited

5,228,000+

Published Research Related to This Trial

Cytomegalovirus (CMV) poses significant health risks to infants and immunocompromised patients, highlighting the need for effective vaccines to prevent CMV-related diseases.

Current research is advancing the development of CMV vaccines, but understanding the specific immune responses needed for effective protection remains crucial before these vaccines can be widely implemented in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress in cytomegalovirus vaccine development. Schleiss, M.[2006]

Peptide vaccination shows promise as a new immunotherapy for treating solid tumors and preventing infections like cytomegalovirus (CMV) in immunosuppressed patients, with a focus on the immunogenic CMV peptide NLVPMVATV.

A novel bio-assay was developed to validate peptide vaccines for their content and bio-activity, demonstrating that the immunogenicity of the vaccine is stable at 4 degrees Celsius but significantly decreases when cryopreserved at -20 degrees Celsius.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytomegalovirus vaccination of leukemia and lymphoma patients after allogeneic stem cell transplantation--validation of a peptide vaccine. Schmitt, A., Bechter, C., Yao, J., et al.[2019]

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]

Certain high-risk groups, such as HIV-infected individuals, transplant patients, and newborns, are particularly vulnerable to diseases caused by human cytomegalovirus (CMV), highlighting the need for effective vaccination strategies.

While there are currently no licensed CMV vaccines for humans, various vaccine approaches, including protein subunit, DNA, and live attenuated vaccines, are being tested in clinical trials, showing promise in inducing protective immune responses against CMV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress toward an elusive goal: current status of cytomegalovirus vaccines. Schleiss, MR., Heineman, TC.[2007]

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]

A universal childhood CMV vaccine could significantly reduce congenital CMV disease by preventing transmission from infected children to mothers, highlighting the importance of early vaccination.

Clinical trials for CMV vaccines should focus on practical endpoints, such as protection against cCMV infection in women and CMV viremia levels in stem cell transplant recipients, to better assess vaccine efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Priorities for CMV vaccine development. Krause, PR., Bialek, SR., Boppana, SB., et al.[2022]

Human cytomegalovirus (CMV) is found in glioblastoma (GBM) tumors but not in normal brain tissue, suggesting that CMV antigens could be effective targets for immunotherapy.

Research shows that T cells specific to the CMV pp65 antigen can recognize and kill GBM tumor cells derived from patients, supporting the potential for CMV-targeted immunotherapies in treating GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunological targeting of cytomegalovirus for glioblastoma therapy. Nair, SK., Sampson, JH., Mitchell, DA.[2021]

The novel PeptiENV cancer vaccine, which incorporates the MMR vaccine, significantly enhances both local and systemic immune responses against tumors when administered directly into the tumor.

Combining PeptiENV therapy with immune checkpoint inhibitors not only improves tumor control and survival rates in mice but also increases the effectiveness of the checkpoint inhibitors, showing that prior immunity to the MMR vaccine does not hinder the cancer treatment's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel cancer vaccine for melanoma based on an approved vaccine against measles, mumps, and rubella. Fusciello, M., Ylösmäki, E., Feola, S., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2039

Outcomes and immune response after peptide vaccination ... PEP-CMV is well-tolerated and elicits an antigen-specific immune response in heavily pretreated, multiply recurrent patients with a 12-month OS of 26.6%.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05096481

Study Details | NCT05096481 | PEP-CMV Vaccine ... This study will address the question of whether targeting CMV antigens with PEP-CMV can serve as a novel immunotherapeutic approach in pediatric patients.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40506525/

A peptide vaccine targeting the CMV antigen pp65 in ... Thirty-six individuals with HGG received PEP-CMV. The mean age was 22.75 ± 9.34 years. The primary outcome, percentage of unacceptable toxicity, ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-07366

A Peptide Vaccine (PEP-CMV) for the Treatment of ... This phase II trial studies how well a peptide vaccine (PEP-CMV) works in treating pediatric patients with newly diagnosed high-grade glioma (HGG) and diffuse ...

5. trials.braintumor.org trials.braintumor.org/trials/NCT05096481

PEP-CMV Vaccine Targeting CMV Antigen to Treat Newly ... This study will address the question of whether targeting CMV antigens with PEP-CMV can serve as a novel immunotherapeutic approach in pediatric patients.

6. nationwidechildrens.org nationwidechildrens.org/research/clinical-research/cancer-clinical-research/neurooncology-studies/connect1906

Pediatric Brain Tumors and Recurrent Medulloblastoma ... The purpose of this phase 2 study is to see if a cancer vaccine (PEP-CMV) can help patients' immune system fight against high-grade glioma and medulloblastoma.