Frameshift Peptides of Children With NF1

NCT04212351 | Completed

• 1 other identifier: Pro00011544
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 3

Brief Summary

The objective of this study is to determine if children and young adults with Neurofibromatosis Type 1 (NF1) and either Low Grade Gliomas (LGGs) or Plexiform Neurofibromas (PNs) have a specific frameshift peptide protein profile and whether a disease specific vaccine created to address these frameshift mutations and variants can be developed. Three study populations will be analyzed; patients with NF1 and active LGGs, NF1 and active PNs, and NF1 and no evidence of active LGGs or PNs. Participation involves a onetime blood draw.

Conditions

Neurofibromatosis Type 1

Outcome Measures

Primary Outcomes (3)

• Measure mean florescent intensity of serum/plasma samples for each cohort by assaying the study samples on frameshift peptide arrays consisting of peptides representing the ~220,000 frameshifts tumors can make in RNA processing.

  All samples will be assayed on the FSP arrays consisting of peptides representing the frameshifts tumors can make in RNA processing. The amount of IgG bound to each feature will be determined as florescent intensity generated by bound secondary antibody. The mean intensity across the 20 subjects for each peptide for each of the 3 groups will be determined. All peptides in the NF1+LGG group with mean intensities greater than 3 SD higher than the mean of the NF1-LGG/PN group will be determined. Those that meet this criterion in more than 3 of the 20 samples will be chosen. The 20 peptides with the highest prevalence across the 20 samples of NF1+LGG will be chosen for the vaccine. If two peptides have the same prevalence, the one with the highest average florescence will be chosen. The same procedure will be applied to determine the 20 peptide components for the NF1+PN vaccine.

  2 years

• Use a feature counting method to establish a mean distinguishable frameshift peptide protein profile for early detection of tumors in patients with NF1.

  The same data as generated in Outcome 1 will be analyzed for the ability to distinguish NF1+LGG and NF1+PN samples from the NF1-LGG/PN samples. Since the antibody reactions to frameshift peptides are stochastic, a feature counting method is employed. A mean is established for each of the NF1-LGG/PN peptides. Any peptide in the NF1+LGG and NF1+PN samples that scores 3 SD higher than NF1-LGG/PN mean is scored as a positive. The total number of positives in the NF1+LGG and NF1+PN pool will be compared to that in the NF1-LGG/PN set. The number of samples that are distinguished by these counts will determine a first pass accuracy estimate of this diagnostic approach as a preamble to an expanded study.

  2 years

• Use a feature counting method to establish a mean distinguishable frameshift peptide protein profile for patient who develop LGGs versus patients who develop PNs.

  The same array data generated in Outcome 1 will be used. The feature counting method used in Outcome 2 will be used to compare the NF1+LGG features to the NF1+PN features. The investigators will determine if there are a set of features that can distinguish the 20 NF1+LGG from the 20 NF1+PN samples. The number of NF1+LGG and NF1+PN samples that can be distinguished will provide a first estimate of accuracy and whether an expanded study is merited.

  2 years

Secondary Outcomes (1)

• Correlate age, gender, family history of NF, disease state (stable, progressive, or improving), and disease history with frameshift peptide profiles, in children and young adults with NF1 and LGGs or PNs.

  2 years

Study Arms (3)

Patients with NF1 and active LGGs

Patients with Neurofibromatosis Type 1 with clinical or radiographic evidence of low grade glioma but no clinical or radiographic evidence of plexiform neurofibroma.

Genetic: Frameshift Array blood sample test

Patients with NF1 and active PNs

Patients with Neurofibromatosis Type 1 with clinical or radiographic evidence of plexiform neurofibroma but no clinical or radiographic evidence of low grade glioma.

Genetic: Frameshift Array blood sample test

Patients with NF1 with no active LGGs or PNs

Patients with Neurofibromatosis Type 1 with no clinical or radiographic evidence of both active plexiform neurofibroma and active low grade glioma.

Genetic: Frameshift Array blood sample test

Interventions

Frameshift Array blood sample test GENETIC

Patient blood test samples will be collected and evaluated for frameshift peptide mutations.

Patients with NF1 and active LGGs; Patients with NF1 and active PNs; Patients with NF1 with no active LGGs or PNs

Eligibility Criteria

• Age: 1 Day - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

There will be a total of 60 patients enrolled in the study. Cohort 1 will consist of 20 subjects with NF1 and active LGG. Cohort 2 will consist of 20 subjects with NF1 and active PN. Cohort 3 will consist of 20 subjects with NF1 and no active LGG or active PN.

You may qualify if:

• Subjects must be between 1 day and 30 years of age, inclusive
• Subjects must either meet clinical criteria for NF1 or have molecular genetic germ line evidence of NF1
• Subject is able to have his/her blood sample drawn within a reasonable period of time after signing consent
• Subjects must either have:
• Active\* LGGs, no active PNs (Cohort 1)
• Active\* PNs, no active LGGs (Cohort 2)
• No active\* LGGs or PNs (Cohort 3) \*Active is defined as any LGG or PN that has shown growth (determined by MRI) in the past 12 months or is causing ongoing symptomatic visual, neurologic, or organ dysfunction or disfigurement as determined by the site investigator.

You may not qualify if:

• \. Patients with NF1 with evidence of both LGG and PN

Sponsors & Collaborators

• Children's National Research Institute: lead
• University of Texas Southwestern Medical Center: collaborator
• Arizona State University: collaborator
• Emory University: collaborator

Study Sites (3)

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

The University of Texas Southwestern Medical Center

Dallas, Texas, 75390-9020, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

A frameshift peptide profile will be determined from patient blood samples

MeSH Terms

Conditions

Neurofibromatosis 1

Condition Hierarchy (Ancestors)

Neurofibromatoses; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Roger J. Packer, MD

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Vice President of Neurology and Behavorial Medicine

Study Record Dates

• First Submitted: May 1, 2019
• First Posted: December 27, 2019
• Study Start: April 11, 2019
• Primary Completion: April 27, 2022
• Study Completion: April 27, 2022
• Last Updated: August 31, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)