DNA Vaccination Against Neuroblastoma

March 1, 2022 updated by: Alexander Meleshko, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology

Pilot Clinical Study of DNA Vaccination Against Neuroblastoma

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
12

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Belarus
    • Minsk Region
      • Minsk, Minsk Region, Belarus, 223053
        • Recruiting
        • Belarussian Research Center for Pediatric Oncology, Hematology and Immunology
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

2 years to 16 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. The diagnosis of neuroblastoma recurrence with morphological / cytological confirmation;
  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 (legal representatives) to participate in this protocol.
  8. Compliance of parents (legal representatives) and the patient himself with participation in the study protocol.

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 and infectious processes, due to which the patient cannot receive treatment in accordance with the study protocol.
  6. 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:

  1. The absence of expression in the tumor tissue of two or more antigens used in the protocol;
  2. The level of peripheral blood leukocytes <1.5 × 10^9 /L, platelet <50.0 × 10^9 /L, Hemoglobin less than 80 g / L;
  3. Positive tests for human immunodeficiency virus (HIV), hepatitis B or C.
  4. Severe impaired liver function - the levels of AST / SGOT or ALT / SGPT exceed the upper limit of normal 5 times or more.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: All subjects
All subjects will receive the vaccine and be followed per the schedule of procedures.
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.
Other Names:
  • DNA-PEI polyplex
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Adverse events experienced by subjects
Time Frame: for 3 months from the first vaccination
To assess the safety of the DNA-PEI and Salmonella vaccines
for 3 months from the first vaccination
Immune response to the vaccine
Time Frame: In check point after 2nd course (9 week after first 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
Time Frame: In check point after 3rd course (14 week after the first 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
Time Frame: up to 4 weeks after the last vaccination
MRD in bone marrow measured by RQ-PCR and flow cytometry
up to 4 weeks after the last vaccination

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression free survival - PFS
Time Frame: Up to 12 months
Time from treatment to date of first documented progression or date of death
Up to 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Belarusian Research Center for Pediatric Oncology, Hematology and Immunology

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Inna V Proleskovskaya, PhD, MD, Belarussian Research Center for Pediatric Oncology, Hematology and Immunology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 9, 2019

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2023

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 31, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 7, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 8, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 2, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 1, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BelarusianPediatric

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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