← Back to Search

Checkpoint Inhibitor

PEP-CMV + Nivolumab for Brain Cancer (PRiME II Trial)

Phase 1 & 2

Waitlist Available

Led By Eric M Thompson, M.D.

Research Sponsored by Washington University School of Medicine

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have received no prior therapy other than surgery, radiation, chemotherapy during radiotherapy and/or steroids

Patients must have adequate bone marrow function

Must not have

Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy

Active infection requiring treatment

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through completion of follow-up (estimated to be 12 years)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new treatment for children and young adults with certain types of brain tumors to see if it is safe and effective. They will be receiving a vaccine along with another type of therapy to

Who is the study for?

This trial is for children and young adults with new or recurrent high-grade gliomas, diffuse midline gliomas, medulloblastoma, or ependymoma. Participants must meet specific health criteria to ensure safety during the trial.

What is being tested?

The study tests a CMV-directed peptide vaccine (PEP-CMV) combined with Nivolumab, an immune checkpoint inhibitor. It also includes Temozolomide chemotherapy and a Tetanus booster to enhance the immune response.

What are the potential side effects?

Possible side effects include typical reactions to vaccines such as soreness at injection site, fever, and fatigue; chemotherapy-related nausea and hair loss; and Nivolumab's potential immune-related issues like skin rash or inflammation in organs.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have only had surgery, radiation, chemotherapy with radiation, or steroids for my condition.

Select...

My bone marrow is functioning well.

Select...

I have a newly diagnosed high-grade glioma or diffuse midline glioma.

Select...

My brain tumor is recurring or not responding to treatment.

Select...

I have enough tumor samples for the trial's tests.

Select...

I am between 4 and 25 years old.

Select...

My kidney function is normal.

Select...

I am mostly active and can care for myself.

Select...

I am mostly capable of self-care and not bedridden.

Select...

I have had treatment, including radiation, for my brain tumor.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I can attend all required follow-up visits and tests.

Select...

I am currently being treated for an infection.

Select...

I have a condition that weakens my immune system.

Select...

My cancer is related to HIV or a solid organ transplant.

Select...

I am taking medication to suppress my immune system for another health condition.

Select...

I have previously participated in a clinical trial where I received treatment.

Select...

I am taking a steroid dose of no more than 4 mg/day.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ through completion of follow-up (estimated to be 12 years)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~through completion of follow-up (estimated to be 12 years)

This trial's timeline: 3 weeks for screening, Varies for treatment, and through completion of follow-up (estimated to be 12 years) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Proportion of patients with unacceptable toxicity

Secondary study objectives

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

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

Overall survival (OS)

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Experimental Treatment

Group I: Phase II: Temozolomide + Nivolumab + PEP-CMV vaccine + Td boosterExperimental Treatment4 Interventions

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.

Group II: Phase I Stratum III: Temozolomide + Nivolumab + PEP-CMV vaccine + Td boosterExperimental Treatment4 Interventions

Patients 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.

Group III: Phase I Stratum II: Temozolomide + Nivolumab + PEP-CMV vaccine + Td boosterExperimental Treatment4 Interventions

Patients 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.

Group IV: Phase I Stratum I: Temozolomide + Nivolumab + PEP-CMV vaccine + Td boosterExperimental Treatment4 Interventions

Patients 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Nivolumab

2015

Completed Phase 3

~4010

Temozolomide

2010

Completed Phase 3

~1880