PEP-CMV Vaccine for Pediatric Brain Tumor

Recruiting at 12 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

Trial Summary

What is the purpose of this trial?

This study will address the question of whether targeting CMV antigens with PEP-CMV can serve as a novel immunotherapeutic approach in pediatric patients with newly-diagnosed high-grade glioma (HGG) or diffuse intrinsic pontine glioma (DIPG) as well as recurrent medulloblastoma (MB). PEP-CMV is a vaccine mixture of a peptide referred to as Component A. Component A is a synthetic long peptide (SLP) of 26 amino acid residues from human pp65. The SLPs encode multiple potential class I, class II, and antibody epitopes across several haplotypes. Component A will be administered as a stable water:oil emulsion in Montanide ISA 51. Funding Source - FDA OOPD

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.

What data supports the effectiveness of the PEP-CMV Vaccine treatment for pediatric brain tumors?

Research on CMV vaccines shows that they can stimulate strong immune responses, which are important for controlling CMV-related diseases. Although specific data on the PEP-CMV Vaccine for pediatric brain tumors is not available, similar CMV vaccines have shown promise in other high-risk groups, like transplant patients, by enhancing immune protection. ^{1 2 3 4 5}

Is the PEP-CMV Vaccine safe for humans?

The CMVPepVax vaccine, which is similar to the PEP-CMV Vaccine, was tested in a small study with patients undergoing stem-cell transplantation. It was found to be safe and helped boost the immune system without needing additional antiviral drugs. ^{1 2 4 5 6}

How is the PEP-CMV Vaccine treatment different from other treatments for pediatric brain tumors?

The PEP-CMV Vaccine is unique because it targets cytomegalovirus (CMV) antigens, which are present in certain brain tumors like glioblastoma but not in normal brain tissue. This vaccine aims to stimulate the immune system to recognize and attack tumor cells, offering a novel approach compared to traditional treatments that do not specifically target CMV antigens. ^{1 4 6 7 8}

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. England 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. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Progress toward an elusive goal: current status of cytomegalovirus vaccines. [2007]

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

Progress in cytomegalovirus vaccine development. [2006]

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

A fusion protein of HCMV IE1 exon4 and IE2 exon5 stimulates potent cellular immunity in an MVA vaccine vector. [2022]

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

Priorities for CMV vaccine development. [2022]

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

A novel cancer vaccine for melanoma based on an approved vaccine against measles, mumps, and rubella. [2022]

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

Immunological targeting of cytomegalovirus for glioblastoma therapy. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Cytomegalovirus vaccination of leukemia and lymphoma patients after allogeneic stem cell transplantation--validation of a peptide vaccine. [2019]