Neoepitope-based Personalized DNA Vaccine Approach in Pediatric Patients With Recurrent Central Nervous System Tumors

NCT03988283 | Recruiting Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: 202211187
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to learn about the safety and feasibility of giving a personalized DNA vaccine to people with central nervous system tumors that have returned or have been resistant to treatment.

Conditions

Pediatric Recurrent Central Nervous System Tumors

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability of adjuvant personalized neoantigen DNA vaccine as measured by the number of grade 3 and 4 adverse events

  Through 30 days after completion of treatment (estimated to be 13 months)

• Feasibility of adjuvant personalized neoantigen DNA vaccine as measured the number of participants that had a neoantigen-specific DNA vaccine generated

  From time of resection to time of initiation (approximately 12-14 weeks)

Secondary Outcomes (2)

• Median Progression Free Survival (PFS)

  2 years

• Median Overall Survival

  2 years

Study Arms (1)

Personalized neoantigen DNA vaccine

EXPERIMENTAL

Patients will receive the vaccine monthly (+/- 3 days) for 6 doses as a priming phase followed by booster injections quarterly Q3mo thereafter. If sufficient quantities of vaccine are available, vaccination may continue until development of intolerance or disease progression in the case of fatal high grade neoplasms or for up to one year. Additionally, patients with non-fatal tumors who complete one year of vaccinations and have stable disease at the completion of treatment will be given the option of resuming vaccinations if they develop subsequent progression.

Biological: Personalized neoantigen DNA vaccine; Device: Papivax Biotech TDS-IM v2.0; Procedure: Peripheral blood draw

Interventions

Personalized neoantigen DNA vaccine BIOLOGICAL

At each vaccination time point, patients will receive one injection of the neoantigen DNA vaccine, one injection into the vastus lateralis.

Personalized neoantigen DNA vaccine

Papivax Biotech TDS-IM v2.0 DEVICE

All study injections will be given intramuscularly using an integrated electroporation device (TDS-IM v2.0 device - Papivax Biotech).

Personalized neoantigen DNA vaccine

Peripheral blood draw PROCEDURE

-After trial enrollment and up to 7 days after the first vaccine dose (baseline); no more than 2 weeks after the 3rd vaccine dose; no more than 2 weeks after the 6th vaccine dose; two weeks after the last dose; time of progression or discontinuation (optional)

Personalized neoantigen DNA vaccine

Eligibility Criteria

• Age: Up to 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Any patient between the ages of 12 and 25 years of age (inclusive) who was diagnosed with a pediatric CNS (brain or spine) of any histologic subtype, who has now developed recurrent or refractory disease.
• All patients enrolled in this trial will receive treatment for recurrent and/or refractory pediatric CNS tumors, including systemic agents, investigational agents, or radiation therapy, prior to receiving the neoantigen DNA vaccine. Co-enrollment to another interventional clinical trial is permitted during the vaccine manufacture period.
• Availability of tissue collected after progression for sequencing to determine presence of targetable neoantigen. This may be fresh tissue collected as part of routine care, another research project or banked fresh frozen samples from tissue obtained at the time of progression from a biopsy, subtotal resection, total gross resection, or re-resection.
• Life expectancy \> 24 weeks.
• Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable) or patient has a guardian who has the ability to understand and willingness to sign an IRB approved written informed consent document.
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, or should a man suspect he has fathered a child, s/he must inform her treating physician immediately.

You may not qualify if:

• A history of other malignancy ≤ 3 years previous with the exception of non-melanoma skin cancer, any in situ cancer that has been successfully resected and cured, treated superficial bladder cancer, or any early-stage solid tumor that was successfully resected without need for adjuvant radiation or chemotherapy.
• Known allergy, or history of serious adverse reaction to, vaccines such as anaphylaxis, hives, or respiratory difficulty.
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• History of immunodeficiency disorder or autoimmune condition requiring active immunosuppressive therapy. This includes inflammatory bowel disease, ulcerative colitis, Crohn's disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis, hemolytic anemia, immune-mediated thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, sarcoidosis, or other rheumatologic disease or any other medical condition or use of medication which might make it difficult for the patient to complete the full course of treatments or to generate an immune response to vaccines.
• Patients with HIV are eligible unless their CD4+ T-cell counts are \< 350 cells/mcL or they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective ART according to DHHS treatment guidelines is recommended.
• Presence of clinically significant increased intracranial pressure (e.g. impending herniation) or hemorrhage, uncontrolled seizures, or requirement for immediate palliative treatment.
• Individuals in whom a measurement of the circumference of the thigh at the midpoint between the hip and knee is \< 35 cm.
• Individuals in whom a skinfold measurement of the cutaneous and subcutaneous tissue for eligible injection sites (left and right vastus laterals muscles) exceeds 50 mm.
• Individuals in whom the ability to observe possible local reactions at the eligible injection sites is, in the opinion of the investigator, unacceptably obscured due to a physical condition (e.g. hypertrophic skin patches, keloids, or other conditions which could interfere with the administration procedure or subsequent assessment of local reactogenicity) or permanent body art.
• Has a metal implant or implantable device within the area of the electroporation injection or has any non-removable electronic stimulation device, such as cardiac demand pacemaker, automatic implantable cardiac defibrillator, nerve stimulator, or deep brain stimulator.
• Acute or chronic, clinically significant hematologic, pulmonary, cardiovascular, or hepatic or renal functional abnormality as determined by the investigator based on medical history, physical examination, EKG, and/or laboratory screening test.
• Any chronic or active neurologic disorder, including seizures and epilepsy, excluding a single febrile seizure as a child.
• Step 2 Eligibility Criteria for Treatment Administration
• Personalized neoantigen DNA vaccine manufactured for administration.
• Karnofsky/Lansky performance status ≥ 60%

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Children's Discovery Institute: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study Officials

• Michael A Huang, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michael A Huang, M.D.

CONTACT

314-454-4146; huangm@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2019
• First Posted: June 17, 2019
• Study Start: October 2, 2024
• Primary Completion (Estimated): March 31, 2029
• Study Completion (Estimated): February 28, 2031
• Last Updated: November 25, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)