NCT04049864

DNA Vaccination Against Neuroblastoma

Pilot Clinical Study of DNA Vaccination Against Neuroblastoma

• Status: Unknown
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Sponsor: Belarusian Research Center for Pediatric Oncology, Hematology and Immunology · Academic / Other
• Sex: All
• Age: 1 Year – 20 Years
• Healthy volunteers: Not accepted

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.

Detailed 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

Conditions

• Relapsed Neuroblastoma

Interventions

Type	Name	Description
BIOLOGICAL	DNA vaccine	conjugate of plasmid DNA with linear polyethylenimine 20 kDa (PEI) One dose includes 400 µg of DNA and 500 µg of PEI.
BIOLOGICAL	Salmonella oral vaccine	suspension 10\^10 CFU of an attenuated Salmonella enterica serovar typhimurium strain (SS2017) containing the plasmid of the corresponding DNA vaccine.
DRUG	Lenalidomide	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.

Timeline

• Start date: 2019-01-09
• Primary completion: 2023-12-31
• Completion: 2023-12-31
• First posted: 2019-08-08
• Last updated: 2022-03-02

Locations

1 site across 1 country: Belarus