PEP-CMV Vaccine Targeting CMV Antigen to Treat Newly Diagnosed Pediatric HGG and DIPG and Recurrent Medulloblastoma

NCT05096481 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: CONNECT1906R01FD007283
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 12

Brief Summary

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

Conditions

High Grade Glioma; Diffuse Intrinsic Pontine Glioma; Recurrent Medulloblastoma

Keywords

High Grade Glioma; Diffuse Intrinsic Pontine Glioma; Recurrent Medulloblastoma; Immunotherapy

Outcome Measures

Primary Outcomes (3)

• 4-mo PFS in patients with recurrent medulloblastoma

  To determine the progression-free survival (PFS) at 4 months in pediatric or young adult patients with recurrent medulloblastoma treated with PEP-CMV.

  4 months

• 1-yr OS in patients with newly diagnosed DIPG

  To estimate the 1-year Overall Survival (OS) distribution in patients with newly diagnosed DIPG treated with radiotherapy followed by PEP-CMV

  one year

• 1-yr PFS in patients with newly diagnosed HGG

  To estimate the 1-year Progression Free Survival (PFS) distribution in patients with newly diagnosed HGG treated with radiotherapy followed by PEP-CMV

  one year

Secondary Outcomes (3)

• ORR in patients with recurrent medulloblastoma

  From Day 1 of treatment through 30 days following end of protocol treatment

• PFS in patients with recurrent medulloblastoma

  one year

• OS in patients with newly diagnosed HGG by PEP-CMV

  2 years

Study Arms (1)

PEP-CMV

EXPERIMENTAL

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.

Biological: PEP-CMV; Drug: Temozolomide; Biological: Tetanus Diphtheria Vaccine

Interventions

PEP-CMV BIOLOGICAL

The PEP-CMV vaccine will be administered as follows: 250 µg/m2 (up to a maximum of 500 µg) of Component A mixed with Montanide ISA-51 (1:1 volume ratio) intradermally administered half in the RIGHT groin and half in the LEFT groin.

PEP-CMV

Temozolomide DRUG

Patients will receive one course of temozolomide 200 mg/m2/day x 5 days on Days 1-5 of cycle 1

Also known as: TMZ

PEP-CMV

Tetanus Diphtheria Vaccine BIOLOGICAL

Patients will receive a tetanus (Td) booster (Td 5 flocculation units, Lf) at the time of enrollment. Immunotherapy begins with a Td pre-conditioning vaccine (Td 1 Lf, in 0.4 mL of saline) delivered i.d. at the RIGHT groin site of the vaccine injection 6-24 hours prior to the first vaccine on day 21.

Also known as: Td

PEP-CMV

Eligibility Criteria

• Age: 3 Years - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age: Patients must be ≥3 and ≤39 years of age at the time of study enrollment
• Diagnosis: Patients must have a diagnosis of medulloblastoma that is recurrent, progressive or refractory. All patients must have histological verification of a medulloblastoma, at original diagnosis or relapse.
• Patients must have measurable disease defined as a lesion that can be measured in two perpendicular diameters on MRI.
• Metastatic Disease: Patients with M+ disease are eligible.
• Performance Status:
• Karnofsky ≥ 50% for patients \>16 years of age or Lansky ≥ 50 for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Prior Therapy:
• Radiotherapy: prior radiotherapy requirements Patients must have received prior disease-directed therapy including radiotherapy for their initial diagnosis of medulloblastoma unless patients are less than 4 years of age at the time of enrollment.
• For those less than 4 years of age at the time of enrollment, prior disease directed therapy does not have to include prior radiotherapy.
• Patients must have had their last fraction of:
• Craniospinal irradiation, total body irradiation or radiation to ≥ 50% of pelvis \> 3 months prior to enrollment.
• Focal irradiation \> 4 weeks prior to enrollment
• Myelosuppressive anticancer therapy: Patients must have received their last dose of myelosuppressive anticancer therapy at least 21 days prior to enrollment
• Immunotherapy: Patients must have received their last dose of any immunotherapy agents at least 30 days prior to enrollment
• Non-myelosuppressive anticancer agents: Patients must have received their last dose of non-myelosuppressive anticancer agents at least 7 days prior to study enrollment.

You may not qualify if:

• Pregnancy or Breast-Feeding:
• Pregnant or breast-feeding women will not be entered on this study due to known or unknown risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-monarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
• Pregnancy Prevention Patients of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study and for 3 months after drug cessation.
• Study Specific:
• Active infection requiring treatment
• Patients with malignancy related to HIV or solid organ transplant: known history of HIV, HBV surface antigen positivity or positive HCV antibody are not eligible. Viral testing is not required unless clinically indicated in patients without a known history
• Known immunosuppressive disease
• Patients with active renal, cardiac (congestive cardiac failure, myocardial infarction, myocarditis), or moderate to severe pulmonary problems generally defined by need for medical intervention (e.g., oxygen, medications) and/or limiting activities of daily living (generally CTCAE Grade 2 or higher) or shortness of breath with limited exertion are not eligible. Pulmonary conditions include (but are not limited to) COPD, asthma, and hemi-pneumectomy
• Patients receiving concomitant immunosuppressive agents for medical conditions; inhaled corticosteroids for asthma are allowed.
• Patients receiving concomitant tumor-directed therapy
• Patients receiving any other investigational drug therapy.
• Patients on dexamethasone \> 0.1 mg/Kg/day up to maximum dose of 4 mg/day or equivalent.
• Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction).
• Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy
• Patients at high risk for imminent neurologic decline due to extensive bulk disease, midline shift, or herniation on MRI. These patients should be discussed with the study chairs.

Sponsors & Collaborators

• Duke University: collaborator
• Nationwide Children's Hospital: lead

Study Sites (12)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

RECRUITING

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

RECRUITING

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

NOT YET RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

NOT YET RECRUITING

St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

RECRUITING

Duke Cancer Center

Durham, North Carolina, 27710, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

NOT YET RECRUITING

Texas Children's Hospital

Houston, Texas, 77030, United States

RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98105, United States

RECRUITING

MeSH Terms

Conditions

Glioma; Diffuse Intrinsic Pontine Glioma; Medulloblastoma

Interventions

Temozolomide; Diphtheria-Tetanus Vaccine

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroectodermal Tumors, Primitive

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures; Diphtheria Toxoid; Toxoids; Tetanus Toxoid; Vaccines, Combined

Study Officials

• Daniel Landi, MD

  Duke Cancer Center

  STUDY CHAIR

• Eric M Thompson, MD

  Washington University - St. Louis Children's Hospital

  STUDY CHAIR

• Maryam Fouladi, MD

  Nationwide Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kelsey H Troyer, PhD

CONTACT

6147223284; kelsey.troyer@nationwidechildrens.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2021
• First Posted: October 27, 2021
• Study Start: July 18, 2024
• Primary Completion (Estimated): June 15, 2028
• Study Completion (Estimated): June 15, 2030
• Last Updated: April 8, 2026

Record last verified: 2026-04

Locations

US (12)