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PEP-CMV + Nivolumab for Newly Diagnosed Diffuse Midline Glioma/High-grade Glioma and Recurrent Diffuse Midline Glioma/High-grade Glioma, Medulloblastoma, and Ependymoma

ConditionsDiffuse Midline GliomaDiffuse Midline High-grade GliomaMedulloblastomaEpendymoma
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age4-25
SponsorWashington University School of Medicine

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Patients must be ≥4 and ≤25 years of age (inclusive) at the time of study enrollment

Metastatic Disease: Patients with M+ disease are eligible.

ANC (Absolute neutrophil count) ≥ 1000/µl.

Platelets ≥ 75,000/µl.

Disqualifiers

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.

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • PEP-CMV vaccine

    Biological/Vaccine

    Intra-dermally administered half in the RIGHT groin and half in the LEFT groin.

  • Tetanus booster

    Biological/Vaccine

    Td 5 flocculation units, Lf

  • Nivolumab

    Biological/Vaccine

    Administered intravenously

  • Temozolomide

    Drug

    Administered orally

Treatment groups

68 Participants
are divided into 4 treatment groups
Group A: Phase I Stratum I: Temozolomide + Nivolumab + PEP-CMV vaccine + Td boosterExperimental treatment 4 interventions
Group B: Phase I Stratum II: Temozolomide + Nivolumab + PEP-CMV vaccine + Td boosterExperimental treatment 4 interventions
Group C: Phase I Stratum III: Temozolomide + Nivolumab + PEP-CMV vaccine + Td boosterExperimental treatment 4 interventions
Group D: Phase II: Temozolomide + Nivolumab + PEP-CMV vaccine + Td boosterExperimental treatment 4 interventions

Trial outcomes

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

Time frame
From the first vaccine (day 21) through 2 weeks after the third vaccine (day 49) (estimated to be 42 days)

Secondary outcomes

1

Mean change in immune response as measured by ELISPOT (IFN-γ) (Phase I only)

For this analysis, the newly diagnosed patients (n=10) will be analyzed separately from the recurrent patients (n=20)

Time frame
Baseline (prior to nivolumab infusion on day 14), cycle 1 day 20, before vaccine #4 (cycle 2 day 1, each cycle is 28 days), every 2 cycles (each cycle is 28 days), and end of treatment (up to 10 years)
2

Median change in immune response as measured by ELISPOT (IFN-γ) (Phase I only)

For this analysis, the newly diagnosed patients (n=10) will be analyzed separately from the recurrent patients (n=20)

Time frame
Baseline (prior to nivolumab infusion on day 14), cycle 1 day 20, before vaccine #4 (cycle 2 day 1, each cycle is 28 days), every 2 cycles (each cycle is 28 days), and end of treatment (up to 10 years))
3

Median overall survival (OS)

OS is defined as time between the start of TMZ Day 1 and death.

Time frame
Through completion of follow-up (estimated to be 20 years)
4

Median progression-free survival (PFS)

PFS is defined as the time between the start of TMZ on Day 1 and first documentation of death or disease progression/recurrence. Patients remaining alive without disease progression will have PFS censored at their last follow-up.

Time frame
Through completion of follow-up (estimated to be 20 years)

Other outcomes

Sponsors and contacts

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Washington University School of Medicine

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Bristol-Myers Squibb

Collaborator

CSBio

Collaborator

Source ClinicalTrials.gov
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