PEP-CMV + Nivolumab for Newly Diagnosed Diffuse Midline Glioma/High-grade Glioma and Recurrent Diffuse Midline Glioma/High-grade Glioma, Medulloblastoma, and Ependymoma
PRiME II
Phase 1/2 Trial of PEP-CMV + Nivolumab for Newly Diagnosed Diffuse Midline Glioma/High-grade Glioma and Recurrent Diffuse Midline Glioma/High-grade Glioma, Medulloblastoma, and Ependymoma (PRiME II)
2 other identifiers
interventional
68
1 country
3
Brief Summary
This is a multisite, phase I/II clinical trial in children and young adults with newly-diagnosed high-grade glioma (HGG), diffuse midline glioma (DMG) and recurrent HGG/DMG, Medulloblastoma (MB), or ependymoma (EPN) to determine the safety, immunogenicity, and efficacy of a CMV-directed peptide vaccine plus checkpoint blockade.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Apr 2026
Longer than P75 for phase_1
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 7, 2024
CompletedFirst Posted
Study publicly available on registry
October 15, 2024
CompletedStudy Start
First participant enrolled
April 30, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2031
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 30, 2043
March 10, 2026
March 1, 2026
5.2 years
October 7, 2024
March 8, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Proportion of patients with unacceptable toxicity
An unacceptable toxicity will be defined as any life-threatening toxicity ≥ Grade 3 that is possibly, probably, or definitely related to the PEP CMV vaccine. There are exceptions listed in the protocol
From the first vaccine (day 21) through 2 weeks after the third vaccine (day 49) (estimated to be 42 days)
Secondary Outcomes (4)
Mean change in immune response as measured by ELISPOT (IFN-γ) (Phase I only)
Before vaccine #1 (day 21), before vaccine #4 (cycle 2 day 1, each cycle is 28 days), every 2 cycles (each cycle is 28 days), and upon removal from therapy (up to 10 years)
Median change in immune response as measured by ELISPOT (IFN-γ) (Phase I only)
Before vaccine #1 (day 21), before vaccine #4 (cycle 2 day 1, each cycle is 28 days), every 2 cycles (each cycle is 28 days), and upon removal from therapy (up to 10 years)
Overall survival (OS)
Through completion of follow-up (estimated to be 12 years)
Progression-free survival (PFS)
Through completion of follow-up (estimated to be 12 years)
Study Arms (4)
Phase I Stratum I: Temozolomide + Nivolumab + PEP-CMV vaccine + Td booster
EXPERIMENTALPatients with newly-diagnosed high-grade glioma or DMG may be enrolled any time within 42 days after completing radiation. Cycle 1 (Induction cycle) is 77±2 days. Will receive 1 course of temozolomide 200 mg/m\^2/day x 5 days on Days 1-5 of cycle 1 \& receive PEP-CMV vaccine at dose level 1 (250 μg/m\^2) on Days 21, 35 ±2 days, and 49 ±2 days. After the induction cycle, each subsequent cycle is 28 days. Starting in cycle 2, PEP-CMV vaccine is administered every 28 days on day 1 of each course. Patient can continue to receive PEP-CMV every 28 days until recurrence/progression. Patients will receive a tetanus (Td) booster at the time of enrollment. Immunotherapy begins with a Td pre-conditioning vaccine delivered 6-24 hours prior to the first vaccine on day 21. Patients will also receive nivolumab 3 mg/kg IV on day 14±1 day then every 14 days ±2 days thereafter.
Phase I Stratum II: Temozolomide + Nivolumab + PEP-CMV vaccine + Td booster
EXPERIMENTALPatients with recurrent/progressive HGG or DMG with measurable disease can be enrolled at any point following recurrence regardless of any prior therapy. Cycle 1 (Induction cycle) is 77±2 days. Will receive 1 course of temozolomide 200 mg/m\^2/day x 5 days on Days 1-5 of cycle 1 \& receive PEP-CMV vaccine at dose level 1 (250 μg/m\^2) on Days 21, 35 ±2 days, and 49 ±2 days. After the induction cycle, each subsequent cycle is 28 days. Starting in cycle 2, PEP-CMV vaccine is administered every 28 days on day 1 of each course. Patient can continue to receive PEP-CMV every 28 days until recurrence/progression. Patients will receive a tetanus (Td) booster at the time of enrollment. Immunotherapy begins with a Td pre-conditioning vaccine delivered 6-24 hours prior to the first vaccine on day 21. Patients will also receive nivolumab 3 mg/kg IV on day 14±1 day then every 14 days ±2 days thereafter.
Phase I Stratum III: Temozolomide + Nivolumab + PEP-CMV vaccine + Td booster
EXPERIMENTALPatients with recurrent/progressive MB or EPN with measurable disease can be enrolled at any point following recurrence regardless of any prior therapy. Cycle 1 (Induction cycle) is 77±2 days. Will receive 1 course of temozolomide 200 mg/m\^2/day x 5 days on Days 1-5 of cycle 1 \& receive PEP-CMV vaccine at dose level 1 (250 μg/m\^2) on Days 21, 35 ±2 days, and 49 ±2 days. After the induction cycle, each subsequent cycle is 28 days. Starting in cycle 2, PEP-CMV vaccine is administered every 28 days on day 1 of each course. Patient can continue to receive PEP-CMV every 28 days until recurrence/progression. Patients will receive a tetanus (Td) booster at the time of enrollment. Immunotherapy begins with a Td pre-conditioning vaccine delivered 6-24 hours prior to the first vaccine on day 21. Patients will also receive nivolumab 3 mg/kg IV on day 14±1 day then every 14 days ±2 days thereafter.
Phase II: Temozolomide + Nivolumab + PEP-CMV vaccine + Td booster
EXPERIMENTALCycle 1 (Induction cycle) is 77±2 days. Will receive 1 course of temozolomide 200 mg/m\^2/day x 5 days on Days 1-5 of cycle 1 \& receive PEP-CMV vaccine at dose level 1 (250 μg/m\^2) on Days 21, 35 ±2 days, and 49 ±2 days. After the induction cycle, each subsequent cycle is 28 days. Starting in cycle 2, PEP-CMV vaccine is administered every 28 days on day 1 of each course. Patient can continue to receive PEP-CMV every 28 days until recurrence/progression. Patients will receive a tetanus (Td) booster at the time of enrollment. Immunotherapy begins with a Td pre-conditioning vaccine delivered 6-24 hours prior to the first vaccine on day 21. Patients will also receive nivolumab 3 mg/kg IV on day 14±1 day then every 14 days ±2 days thereafter.
Interventions
Intra-dermally administered half in the RIGHT groin and half in the LEFT groin.
Td 5 flocculation units, Lf
Administered intravenously
Administered orally
Eligibility Criteria
You may qualify if:
- Patients must be ≥4 and ≤25 years of age (inclusive) at the time of study enrollment
- Metastatic Disease: Patients with M+ disease are eligible.
- Adequate bone marrow function defined as:
- ANC (Absolute neutrophil count) ≥ 1000/µl.
- Platelets ≥ 75,000/µl.
- Hemoglobin \> 8 g/dL. (may be supported)
- Adequate renal function defined as:
- Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m\^2 OR A serum creatinine based on age/gender as listed in the protocol. Note: The threshold creatinine values in this table were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the CDC.
- Adequate liver function defined as:
- Total bilirubin ≤1.5 times institutional ULN
- AST(SGOT) ≤3 × institutional upper limit of normal
- ALT(SGPT) ≤3 × institutional upper limit of normal
- The effects of PEP-CMV and nivolumab on the developing human fetus are unknown. For this reason, female participants of childbearing potential and male participants who are sexually active must agree to use adequate contraception prior to study entry, for the duration of study participation, and for at least 5 months after completion of study participation. Should a female participant become pregnant or suspect she is pregnant while participating in this study, or should a male participant suspect he has fathered a child, s/he must inform the treating physician immediately.
- Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants. All patients and/or their parents or legal guardians must sign an IRB approved written informed consent document.
- Stratum I patients must have histologically confirmed, newly-diagnosed HGG (such as anaplastic astrocytoma, glioblastoma) or newly-diagnosed DMG (such H3K27M mutant diffuse midline glioma).
- +33 more criteria
You may not qualify if:
- 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 and women who are post-menarchal at least 7 days prior to study enrollment. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method, which includes abstinence.
- 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 unrelated systemic illness including but not limited to renal, hepatic 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.
- Previous enrollment and treatment on an interventional clinical trial (Stratum 1 only).
- Patients on dexamethasone \> 0.1 mg/Kg/day up to maximum dose of 4 mg/day or equivalent.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (3)
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Eric M Thompson, M.D.
Washington University School of Medicine
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 7, 2024
First Posted
October 15, 2024
Study Start
April 30, 2026
Primary Completion (Estimated)
June 30, 2031
Study Completion (Estimated)
April 30, 2043
Last Updated
March 10, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Immediately following publication without an end day.
- Access Criteria
- Anyone may access data that is published.
Individual participant data collected during the trial, after deidentification may be shared between enrolling sites (WashU, Duke, MD Anderson).