DNA Vaccination Against Neuroblastoma

NCT04049864 | Unknown Early Phase 1 DMC

• 1 other identifier: BelarusianPediatric
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is pilot open-label study to evaluate the safety and immunogenicity of a DNA vaccine strategy in relapsed neuroblastoma patients following chemotherapy and HSC transplantation. The combined form of the vaccine includes an intramuscular injection of the DNA-polyethylenimine conjugate and oral administration using the attenuated Salmonella enterica as DNA vaccine carriers. Objectives of the study:

1. 1.To assess safety and document local and systemic toxicity to combined DNA vaccine
2. 2.To determine immunogenicity of the vaccine
3. 3.To evaluate clinical response to vaccination. Control of minimal residual disease in bone marrow and duration of remission.

Conditions

Relapsed Neuroblastoma

Keywords

neuroblastoma; DNA vaccine; Salmonella vaccine; polyethylenimine

Outcome Measures

Primary Outcomes (4)

• Adverse events experienced by subjects

  To assess the safety of the DNA-PEI and Salmonella vaccines

  for 3 months from the first vaccination

• Immune response to the vaccine

  Immunogenicity will be evaluated by assessing T-cell IFN-γ production in ELISPOT and PVXCP antibody production by ELISA

  In check point after 2nd course (9 week after first vaccine)

• Immune response to the vaccine

  Immunogenicity will be evaluated by assessing T-cell IFN-γ production in ELISPOT and PVXCP antibody production by ELISA

  In check point after 3rd course (14 week after the first vaccine)

• Minimal residual disease - MRD

  MRD in bone marrow measured by RQ-PCR and flow cytometry

  up to 4 weeks after the last vaccination

Secondary Outcomes (1)

• Progression free survival - PFS

  Up to 12 months

Study Arms (1)

All subjects

EXPERIMENTAL

All subjects will receive the vaccine and be followed per the schedule of procedures.

Biological: DNA vaccine; Biological: Salmonella oral vaccine; Drug: Lenalidomide

Interventions

DNA vaccine BIOLOGICAL

conjugate of plasmid DNA with linear polyethylenimine 20 kDa (PEI) One dose includes 400 µg of DNA and 500 µg of PEI.

Also known as: DNA-PEI polyplex

All subjects

Salmonella oral vaccine BIOLOGICAL

suspension 10\^10 CFU of an attenuated Salmonella enterica serovar typhimurium strain (SS2017) containing the plasmid of the corresponding DNA vaccine.

All subjects

Lenalidomide DRUG

Lenalidomide is prescribed in a dose of 25 mg / day in a course of three weeks starting 7 days before the first vaccination course and ending on the day of the last vaccination course.

All subjects

Eligibility Criteria

• Age: 1 Year - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• The diagnosis of neuroblastoma recurrence with morphological / cytological confirmation;
• The presence of tumor tissue for biopsy;
• The absence of progression or a large tumor mass (bulky disease);
• The physical status on the scale of ECOG 0 - 2.
• Life expectancy of at least 12 months
• Indicators of cellular immunity of the blood: lymphocytes - at least 1 \* 10\^9;
• Availability of written informed consent of the patient and his parents (legal representatives) to participate in this protocol.
• Compliance of parents (legal representatives) and the patient himself with participation in the study protocol.

You may not qualify if:

• A. Based on the anamnesis:
• The presence of any primary immunodeficiency;
• The presence of a primary multiple malignant tumor;
• The presence of autoimmune diseases in history (except thyroiditis);
• Polyalgia;
• Severe diseases, including those with severe symptoms, untreated inflammatory and infectious processes, due to which the patient cannot receive treatment in accordance with the study protocol.
• Socioeconomic or geographical circumstances that cannot guarantee proper compliance with the requirements of the protocol for treatment and further observation.
• B. based on survey data:
• The absence of expression in the tumor tissue of two or more antigens used in the protocol;
• The level of peripheral blood leukocytes \<1.5 × 10\^9 /L, platelet \<50.0 × 10\^9 /L, Hemoglobin less than 80 g / L;
• Positive tests for human immunodeficiency virus (HIV), hepatitis B or C.
• Severe impaired liver function - the levels of AST / SGOT or ALT / SGPT exceed the upper limit of normal 5 times or more.

Sponsors & Collaborators

• Belarusian Research Center for Pediatric Oncology, Hematology and Immunology: lead

Study Sites (1)

Belarussian Research Center for Pediatric Oncology, Hematology and Immunology

Minsk, Minsk Oblast, 223053, Belarus

RECRUITING

MeSH Terms

Conditions

Neuroblastoma

Interventions

Vaccines, DNA; Lenalidomide

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Vaccines; Biological Products; Complex Mixtures; Antigens; Biological Factors; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Inna V Proleskovskaya, PhD, MD

  Belarussian Research Center for Pediatric Oncology, Hematology and Immunology

  STUDY DIRECTOR

Central Study Contacts

Alexander N Meleshko, PhD

CONTACT

+375296940023; alexander.meleshko@gmail.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 31, 2019
• First Posted: August 8, 2019
• Study Start: January 9, 2019
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: March 2, 2022

Record last verified: 2022-03

Locations

BE (1)