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

Plain English Summary

PEP-CMV Vaccine Targeting CMV Antigen to Treat Newly Diagnosed Pediatric HGG and DIPG and Recurrent Medulloblastoma is a Phase 2 clinical trial sponsored by Nationwide Children's Hospital studying High Grade Glioma, Diffuse Intrinsic Pontine Glioma, Recurrent Medulloblastoma. This trial tests a new vaccine called PEP-CMV to help the body fight certain aggressive brain cancers in children. It is for children aged 3 to 39 diagnosed with newly diagnosed high-grade glioma, newly diagnosed diffuse intrinsic pontine glioma, or recurrent medulloblastoma. Participation involves receiving the PEP-CMV vaccine, and potentially chemotherapy, with regular check-ups and tests. Alternative treatments may include surgery, radiation, chemotherapy, and targeted therapies, depending on the specific diagnosis and stage of the cancer. The trial aims to enroll 120 participants.

Official 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

Who Can Participate

Here is what you need to know about eligibility for this trial. Children aged 3 to 39 years old with specific types of brain tumors (high-grade glioma, DIPG, or medulloblastoma) can join. Patients must have a confirmed diagnosis and meet certain health and organ function requirements. Those with recurrent medulloblastoma must have measurable disease and have completed prior treatments according to specific timelines. Patients with newly diagnosed DIPG can join if their tumor is typical in appearance on MRI, even without a biopsy. This trial is studying High Grade Glioma, Diffuse Intrinsic Pontine Glioma, Recurrent Medulloblastoma, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcomes measure how long patients live without their cancer getting worse (PFS) or how long they live overall (OS) at specific time points, indicating how effective the vaccine might be i The specific primary outcome measures are: 4-mo PFS in patients with recurrent medulloblastoma (4 months); 1-yr OS in patients with newly diagnosed DIPG (one year); 1-yr PFS in patients with newly diagnosed HGG (one year). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial explores a new way to treat aggressive pediatric brain tumors by using the body's own immune system to fight cancer, addressing a significant unmet need in these difficult-to-treat conditio Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets High Grade Glioma, Diffuse Intrinsic Pontine Glioma, Recurrent Medulloblastoma, where improved treatment options are needed.

Investor Insight

This trial targets a rare but aggressive group of pediatric cancers, representing a significant unmet medical need. Success could lead to a novel immunotherapy approach, potentially opening a new mark Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of the PEP-CMV vaccine and any other treatments involved. Understand the schedule of appointments, tests, and vaccine administration, and how it might affect daily life. Discuss any concerns about side effects and how they will be managed during the trial. This trial is currently recruiting participants. The trial is being conducted at 12 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 120 participants

Interventions

• 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.

Primary Outcomes

• 4-mo PFS in patients with recurrent medulloblastoma (4 months)
• 1-yr OS in patients with newly diagnosed DIPG (one year)
• 1-yr PFS in patients with newly diagnosed HGG (one year)

Secondary Outcomes

• ORR in patients with recurrent medulloblastoma (From Day 1 of treatment through 30 days following end of protocol treatment)
• PFS in patients with recurrent medulloblastoma (one year)
• OS in patients with newly diagnosed HGG by PEP-CMV (2 years)

Full Eligibility Criteria

Inclusion Criteria for patients with recurrent /progressive medulloblastoma (stratum I)

1. Age: Patients must be ≥3 and ≤39 years of age at the time of study enrollment
2. Diagnosis: Patients must have a diagnosis of medulloblastoma that is recurrent, progressive or refractory. All patients must have histological verification of a medulloblastoma, at original diagnosis or relapse.

   • Patients must have measurable disease defined as a lesion that can be measured in two perpendicular diameters on MRI.
3. Metastatic Disease: Patients with M+ disease are eligible.
4. Performance Status:

   Karnofsky ≥ 50% for patients \>16 years of age or Lansky ≥ 50 for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
5. Prior Therapy:

   1. Radiotherapy: prior radiotherapy requirements Patients must have received prior disease-directed therapy including radiotherapy for their initial diagnosis of medulloblastoma unless patients are less than 4 years of age at the time of enrollment.

      For those less than 4 years of age at the time of enrollment, prior disease directed therapy does not have to include prior radiotherapy.

      Patients must have had their last fraction of:
      * Craniospinal irradiation, total body irradiation or radiation to ≥ 50% of pelvis \> 3 months prior to enrollment.
      * Focal irradiation \> 4 weeks prior to enrollment
   2. Myelosuppressive anticancer therapy: Patients must have received their last dose of myelosuppressive anticancer therapy at least 21 days prior to enrollment
   3. Immunotherapy: Patients must have received their last dose of any immunotherapy agents at least 30 days prior to enrollment
   4. Non-myelosuppressive anticancer agents: Patients must have received their last dose of non-myelosuppressive anticancer agents at least 7 days prior to study enrollment.
   5. Antibodies: Patients must have received their last dose of any antibodies at least 21 days prior to enrollment.
   6. Hematopoietic growth factors: Patients must have received their last dose of hematopoietic growth factors at least 14 days prior to enrollment for a long-acting growth factor (e.g. pegfilgrastim) or 7 days prior to enrollment for short-acting growth factor.
   7. Autologous stem cell infusion: At least 90 days must have elapsed after an autologous stem cell infusion
6. Organ Function Requirements:

   1. Adequate bone marrow function defined as:

      * ANC (Absolute neutrophil count) ≥ 1000/µl.
      * Platelets ≥ 100,000/µl. (may be supported)
      * Hemoglobin \> 8 g/dL. (may be supported)
   2. Adequate Renal Function defined as: Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 or A serum creatinine based on age/gender as follows:

      Age: Maximum Serum Creatinine (mg/dL)
      * 2 to \< 6 years: 0.8 (Male) 0.8 (Female)
      * 6 to \< 10 years: 1 (Male) 1 (Female)
      * 10 to \< 13 years: 1.2 (Male) 1.2 (Female)
      * 13 to \< 16 years: 1.5 (Male) 1.4 (Female)
      * ≥ 16 years: 1.7 (Male) 1.4 (Female)
   3. 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
   4. Adequate Neurological Function Defined as

      * Patients with neurological deficits should have deficits that are stable for a minimum of 2 weeks prior to enrollment.
      * Patients with current seizure disorders may be enrolled if seizures are well- controlled on antiepileptic therapies.
   5. Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study and for three months after drug cessation.
   6. Signed informed consent according to institutional guidelines must be obtained prior to enrollment.

Inclusion Criteria for Patients with Newly-Diagnosed High-Grade Gliomas (HGG) (stratum II, NOT CURRENTLY ENROLLING) and Newly-Diagnosed (DIPG) (stratum III)

1. Age: Patients must be ≥3 and ≤39 years of age at the time of study enrollment
2. Diagnosis

   1. Stratum II (NOT CURRENTLY ENROLLING): patients must have histologically confirmed, newly-diagnosed HGG (such as anaplastic astrocytoma, glioblastoma, H3K27-altered DMG).

      * Patients with a newly-diagnosed HGG must enroll within 6 weeks of their final dose of standard radiation therapy with or without chemotherapy.
      * Patients with primary spinal cord tumors are eligible
   2. Stratum III: Patients with a newly-diagnosed DIPG:

      * Patients with a radiographically typical DIPG, defined as a tumor with a pontine epicenter and diffuse involvement of more than 2/3 of the pons, are eligible without histologic confirmation.
      * Patients with brainstem lesions that do not meet these radiographic criteria will be eligibl

Trial Locations

• Children's Hospital Colorado, Aurora, Colorado, United States
• Children's National Medical Center, Washington D.C., 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, St 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
• ...and 2 more locations

Frequently Asked Questions

Related Conditions

• Pediatric Brain Tumors
• High-Grade Glioma
• Diffuse Intrinsic Pontine Glioma (DIPG)
• Medulloblastoma
• Pediatric Oncology
• Immunotherapy
• Cancer Vaccines
• Cytomegalovirus (CMV)
• Central Nervous System Tumors
• Pediatric Cancer Research

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