PEP-CMV Vaccine Targeting CMV Antigen to Treat Newly Diagnosed Pediatric HGG and DIPG and Recurrent Medulloblastoma
- Conditions
- High Grade GliomaDiffuse Intrinsic Pontine GliomaRecurrent Medulloblastoma
- Interventions
- Registration Number
- NCT05096481
- Lead Sponsor
- Nationwide Children's Hospital
- 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
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 120
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description PEP-CMV Temozolomide 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 Tetanus Diphtheria Vaccine 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 PEP-CMV 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.
- Primary Outcome Measures
Name Time Method 1-yr OS in patients with newly diagnosed DIPG one year To estimate the 1-year Overall Survival (OS) distribution in patients with newly diagnosed DIPG treated with radiotherapy followed by PEP-CMV
1-yr PFS in patients with newly diagnosed HGG one year To estimate the 1-year Progression Free Survival (PFS) distribution in patients with newly diagnosed HGG treated with radiotherapy followed by PEP-CMV
4-mo PFS in patients with recurrent medulloblastoma 4 months To determine the progression-free survival (PFS) at 4 months in pediatric or young adult patients with recurrent medulloblastoma treated with PEP-CMV.
- Secondary Outcome Measures
Name Time Method OS in patients with newly diagnosed HGG by PEP-CMV 2 years To determine the 2-year Overall Survival (OS) in patients newly diagnosed with HGG treated with PEP-CMV.
ORR in patients with recurrent medulloblastoma From Day 1 of treatment through 30 days following end of protocol treatment To determine the objective response rate (ORR) = partial response (PR) + complete response (CR) in patients with recurrent medulloblastoma treated with PEP-CMV
PFS in patients with recurrent medulloblastoma one year To determine the 1-year Progression Free Survival (PFS) in patients with recurrent Medulloblastoma treated with PEP-CMV.
Trial Locations
- Locations (12)
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Nicklaus Children's Hospital
🇺🇸Miami, Florida, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
St. Louis Children's Hospital
🇺🇸Saint Louis, Missouri, United States
Duke Cancer Center
🇺🇸Durham, North Carolina, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States