Relapsed NeuroblastomaEarly Phase 1NCT04049864
DNA Vaccination Against Neuroblastoma
A Early Phase 1 study testing DNA vaccine, Salmonella oral vaccine and Lenalidomide in people with Relapsed Neuroblastoma, run by Belarusian Research Center for Pediatric Oncology, Hematology and Immunology at 1 site in Belarus.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year to 20 years
- Conditions the study is for
- Relapsed Neuroblastoma
- What is being tested?
- DNA vaccine, Salmonella oral vaccine and Lenalidomide
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteBelarus
- Study dates
- 9 Jan 2019to 31 Dec 2023
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 12Show fewer
- Socioeconomic or geographical circumstances that cannot guarantee proper compliance with the requirements of the protocol for treatment and further observation.
- 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.
Trial locations and contacts
1 site in 1 country.
Belarus1 site, 1 recruiting
- Recruiting
Belarussian Research Center for Pediatric Oncology, Hematology and Immunology
Minsk, Minsk Oblast, 223053
+375 17 265 42 22, mail@oncology.by
About this study
Official title: 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:
- 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.
Read the 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
- Being tested
- DNA vaccine, Salmonella oral vaccine, Lenalidomide
- Keywords
- neuroblastoma, DNA vaccine, Salmonella vaccine, polyethylenimine
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DNA vaccineBiological
Also called DNA-PEI polyplex
conjugate of plasmid DNA with linear polyethylenimine 20 kDa (PEI) One dose includes 400 µg of DNA and 500 µg of PEI.
Salmonella oral vaccineBiological
suspension 10^10 CFU of an attenuated Salmonella enterica serovar typhimurium strain (SS2017) containing the plasmid of the corresponding DNA vaccine.
LenalidomideDrug
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 group | Role | What they receive |
|---|---|---|
| All subjects | Experimental | All subjects will receive the vaccine and be followed per the schedule of procedures. Receives: Biological: DNA vaccine; Biological: Salmonella oral vaccine; Drug: Lenalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events experienced by subjects
To assess the safety of the DNA-PEI and Salmonella vaccines
Measured: 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
Measured: 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
Measured: 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
Measured: up to 4 weeks after the last vaccination
Secondary outcomes (1)
Progression free survival - PFS
Time from treatment to date of first documented progression or date of death
Measured: Up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2019
- Study start9 Jan 2019
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed NeuroblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alexander Meleshko, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
- Investigators
- Inna V Proleskovskaya, PhD, MD, Study director, Belarussian Research Center for Pediatric Oncology, Hematology and Immunology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04049864
- Sponsor's protocol ID
- BelarusianPediatric
- Status last verified
- Mar 2022
- First submitted
- 31 Jul 2019
- Last updated
- 2 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Clinical Study of DNA Vaccination Against Neuroblastoma
- ClinicalTrials.gov ID
- NCT04049864
- Acronym / sponsor ID
- BelarusianPediatric
- Conditions
- Relapsed Neuroblastoma
- Keywords
- neuroblastoma, DNA vaccine, Salmonella vaccine, polyethylenimine
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Belarusian Research Center for Pediatric Oncology, Hematology and ImmunologyUniversity, hospital or other
- Study start
- 9 Jan 2019 (actual)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 8 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All subjects | Experimental | Biological: DNA vaccine, Biological: Salmonella oral vaccine, Drug: LenalidomideAll subjects will receive the vaccine and be followed per the schedule of procedures. |
Who may qualify
- Ages
- 1 year to 20 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (12 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DNA vaccineAlso: DNA-PEI polyplexconjugate of plasmid DNA with linear polyethylenimine 20 kDa (PEI) One dose includes 400 µg of DNA and 500 µg of PEI. | Biological | All subjects |
| Salmonella oral vaccinesuspension 10^10 CFU of an attenuated Salmonella enterica serovar typhimurium strain (SS2017) containing the plasmid of the corresponding DNA vaccine. | Biological | All subjects |
| LenalidomideLenalidomide 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. | Drug | All subjects |
Primary outcome
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
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
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
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
1 secondary outcome
Progression free survival - PFS
Time frame: Up to 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Inna V Proleskovskaya, PhD, MD study director
Belarussian Research Center for Pediatric Oncology, Hematology and Immunology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing DNA vaccine, Salmonella oral vaccine and Lenalidomide in people with Relapsed Neuroblastoma, run by Belarusian Research Center for Pediatric Oncology, Hematology and Immunology at 1 site in Belarus.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belarus. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Alexander N Meleshko, PhD (+375296940023, alexander.meleshko@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events experienced by subjects (time frame: for 3 months from the first vaccination). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2022.