NCT05096481

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

Phase 2 Trial of a Novel Peptide Vaccine (PEP-CMV) Targeting CMV Antigen for Newly Diagnosed Pediatric High-grade Glioma and Diffuse Intrinsic Pontine Glioma and Recurrent Medulloblastoma

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Sponsor: Nationwide Children's Hospital · Academic / Other
• Sex: All
• Age: 3 Years – 39 Years
• Healthy volunteers: Not accepted

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

Detailed description

This phase II clinical trial will have 3 strata in order to assess the efficacy of a highly immunogenic CMV-directed peptide vaccines in children with (1) recurrent medulloblastoma (rMB), (2) newly-diagnosed high-grade gliomas (HGG) and (3) newly-diagnosed diffuse intrinsic pontine glioma (DIPG). Each stratum will run independently with a different endpoint and statistical design. Within each stratum, the populations that may be used for analysis are defined as: * Safety Analysis: Patients who receive at least 1 dose of the treatment will be used for safety analyses. * Efficacy Analysis: Patients who receive at least 1 dose of the treatment will be used for efficacy analyses. Stratum I: Patients with recurrent medulloblastoma with measurable disease (see eligibility) can be enrolled at any point following recurrence regardless of any prior therapy. For the purpose of this study, recurrence will be defined as a new lesion confirmed by biopsy or resection, positive cerebrospinal fluid (CSF) cytology, or recurrent/progressive tumor on MRI. Strata II and III: Patients with newly-diagnosed high-grade glioma or DIPG may be enrolled any time within 42 days after completing radiation. Cycle 1 (Induction cycle) is 77±2 days. Patients will receive one course of temozolomide 200 mg/m2/day x 5 days on Days 1-5 of cycle 1 and receive PEP-CMV vaccine intradermally at dose level 1 (250 μg/m2 ) on Days 21, 35 ±2 days, and 49 ±2 days. After the induction cycle which is 77 ± 2 days, each subsequent cycle is 28 days. Starting in cycle 2, PEP-CMV vaccine is administered intradermally every 28 days on day 1 of each course. Patient can continue to receive PEP-CMV every 28 days for a total of 24 cycles. 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. 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.

Conditions

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

Interventions

Type	Name	Description
BIOLOGICAL	PEP-CMV	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.
DRUG	Temozolomide	Patients will receive one course of temozolomide 200 mg/m2/day x 5 days on Days 1-5 of cycle 1
BIOLOGICAL	Tetanus Diphtheria Vaccine	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.

Timeline

• Start date: 2024-07-18
• Primary completion: 2028-06-15
• Completion: 2030-06-15
• First posted: 2021-10-27
• Last updated: 2026-04-08

Locations

12 sites across 1 country: United States

Regulatory

• FDA-regulated drug study