Back to resultsDNA Vaccination Against Neuroblastoma
Primary Purpose
Relapsed Neuroblastoma
Status
Recruiting
Phase
Early Phase 1
Locations
Belarus
Study Type
Interventional
Intervention
DNA vaccine
Salmonella oral vaccine
Lenalidomide
Sponsored by
About this trial
This is an interventional treatment trial for Relapsed Neuroblastoma focused on measuring neuroblastoma, DNA vaccine, Salmonella vaccine, polyethylenimine
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
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.
Sites / Locations
- Belarussian Research Center for Pediatric Oncology, Hematology and ImmunologyRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
All subjects
Arm Description
All subjects will receive the vaccine and be followed per the schedule of procedures.
Outcomes
Primary Outcome Measures
Adverse events experienced by subjects
To assess the safety of the DNA-PEI and Salmonella vaccines
Immune response to the vaccine
Immunogenicity will be evaluated by assessing T-cell IFN-γ production in ELISPOT and PVXCP antibody production by ELISA
Immune response to the vaccine
Immunogenicity will be evaluated by assessing T-cell IFN-γ production in ELISPOT and PVXCP antibody production by ELISA
Minimal residual disease - MRD
MRD in bone marrow measured by RQ-PCR and flow cytometry
Secondary Outcome Measures
Progression free survival - PFS
Time from treatment to date of first documented progression or date of death
Full Information
NCT ID
NCT04049864
First Posted
July 31, 2019
Last Updated
March 1, 2022
Sponsor
Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
1. Study Identification
Unique Protocol Identification Number
NCT04049864
Brief Title
DNA Vaccination Against Neuroblastoma
Official Title
Pilot Clinical Study of DNA Vaccination Against Neuroblastoma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 9, 2019 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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:
To assess safety and document local and systemic toxicity to combined DNA vaccine
To determine immunogenicity of the vaccine
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed Neuroblastoma
Keywords
neuroblastoma, DNA vaccine, Salmonella vaccine, polyethylenimine
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
All subjects
Arm Type
Experimental
Arm Description
All subjects will receive the vaccine and be followed per the schedule of procedures.
Intervention Type
Biological
Intervention Name(s)
DNA vaccine
Other Intervention Name(s)
DNA-PEI polyplex
Intervention Description
conjugate of plasmid DNA with linear polyethylenimine 20 kDa (PEI) One dose includes 400 µg of DNA and 500 µg of PEI.
Intervention Type
Biological
Intervention Name(s)
Salmonella oral vaccine
Intervention Description
suspension 10^10 CFU of an attenuated Salmonella enterica serovar typhimurium strain (SS2017) containing the plasmid of the corresponding DNA vaccine.
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Intervention Description
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.
Primary Outcome Measure Information:
Title
Adverse events experienced by subjects
Description
To assess the safety of the DNA-PEI and Salmonella vaccines
Time Frame
for 3 months from the first vaccination
Title
Immune response to the vaccine
Description
Immunogenicity will be evaluated by assessing T-cell IFN-γ production in ELISPOT and PVXCP antibody production by ELISA
Time Frame
In check point after 2nd course (9 week after first vaccine)
Title
Immune response to the vaccine
Description
Immunogenicity will be evaluated by assessing T-cell IFN-γ production in ELISPOT and PVXCP antibody production by ELISA
Time Frame
In check point after 3rd course (14 week after the first vaccine)
Title
Minimal residual disease - MRD
Description
MRD in bone marrow measured by RQ-PCR and flow cytometry
Time Frame
up to 4 weeks after the last vaccination
Secondary Outcome Measure Information:
Title
Progression free survival - PFS
Description
Time from treatment to date of first documented progression or date of death
Time Frame
Up to 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alexander N Meleshko, PhD
Phone
+375296940023
Email
alexander.meleshko@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Inna V Proleskovskaya, PhD, MD
Organizational Affiliation
Belarussian Research Center for Pediatric Oncology, Hematology and Immunology
Official's Role
Study Director
Facility Information:
Facility Name
Belarussian Research Center for Pediatric Oncology, Hematology and Immunology
City
Minsk
State/Province
Minsk Region
ZIP/Postal Code
223053
Country
Belarus
Individual Site Status
Recruiting
Facility Contact:
Phone
+375 17 265 42 22
Email
mail@oncology.by
12. IPD Sharing Statement
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DNA Vaccination Against Neuroblastoma
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