DNA Vaccination Against Neuroblastoma

Last updated: March 1, 2022
Sponsor: Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
Overall Status: Active - Recruiting

Phase

1

Condition

Neuroblastoma

Treatment

N/A

Clinical Study ID

NCT04049864
BelarusianPediatric
  • Ages 1-20
  • All Genders

Study 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. To assess safety and document local and systemic toxicity to combined DNA vaccine

  2. To determine immunogenicity of the vaccine

  3. To evaluate clinical response to vaccination. Control of minimal residual disease in bone marrow and duration of remission.

Eligibility Criteria

Inclusion

Inclusion Criteria:

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

Exclusion

Exclusion Criteria: A. Based on the anamnesis:

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

Study Design

Total Participants: 12
Study Start date:
January 09, 2019
Estimated Completion Date:
December 31, 2023

Study Description

DNA vaccine construction includes chimeric fusion of neuroblastoma-associated antigen and potato virus X coat protein (PVXCP) as an immune enhancer. In each course vaccine for one antigen is applies. The selection of antigens is carried out after analyzing of their expression in the tumor biopsy material by PCR and IHC. The list of antigens used in the study: tyrosine hydroxylase (TH), Phox2B, Survivin, MAGEA1, MAGEA3, PRAME. The antigens with the highest level of expression in the tumor sample of each patient are selected for vaccination.

Vaccination schedule for each patient includes three courses of vaccination. One course includes three administrations of vaccines against a single antigen. Vaccination is repeated at intervals of 1 week (plus minus 3 working days). Break between courses - 3-4 weeks. Each vaccination includes an injection and taking a capsule with a dose of bacteria.

For intramuscular injection, we use conjugate (polyplex) DNA with linear polyethylenimine 20 kDa (PEI). One dose includes 400 µg of DNA and 500 µg of PEI. When administered orally, the patient receives a suspension 10^10 CFU of an attenuated Salmonella enterica serovar typhimurium strain (SS2017) containing the plasmid of the corresponding DNA vaccine.

Before and during vaccination, an accompanying chemotherapy is carried out, including cyclophosphamide, propranolol, celecoxib and lenalidomide. Cyclophosphamide is prescribed three days before the start of each vaccination course in a single dose of 300 mg / m2. 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

Connect with a study center

  • Belarussian Research Center for Pediatric Oncology, Hematology and Immunology

    Minsk, Minsk Region 223053
    Belarus

    Active - Recruiting

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