RECRUITING

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

Conditions

Pediatric Recurrent Central Nervous System Tumors

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Pilot Study to Assess the Safety, Feasibility, and Preliminary Efficacy of a Neoepitope-based Personalized DNA Vaccine Approach in Pediatric Patients With Recurrent Central Nervous System Tumors

Quick Facts

Study Start:2024-10-02

Study Completion:2031-02-28

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03988283

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:Not specified to 25 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
* 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.	* 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.

Inclusion Criteria

Exclusion Criteria

* 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.

* 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.

Contacts and Locations

Study Contact

Michael A Huang, M.D.

CONTACT

314-454-4146

huangm@wustl.edu

Principal Investigator

Michael A Huang, M.D.

PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Study Locations (Sites)

Washington University School of Medicine

St Louis, Missouri, 63110

United States

Collaborators and Investigators

Sponsor: Washington University School of Medicine

Michael A Huang, M.D., PRINCIPAL_INVESTIGATOR, Washington University School of Medicine

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-10-02

Study Completion Date2031-02-28

Study Record Updates

Study Start Date2024-10-02

Study Completion Date2031-02-28

Terms related to this study

Additional Relevant MeSH Terms

Pediatric Recurrent Central Nervous System Tumors