Phase I clinical trial of idiotypic DNA vaccination in patients with B-cell lymphoma

ISRCTN ISRCTN31090206
DOI https://doi.org/10.1186/ISRCTN31090206
Secondary identifying numbers Protocol reg.# 20142755
Submission date
12/11/2016
Registration date
24/11/2016
Last edited
28/07/2022
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and study aims
Vaccination against cancer can help the body’s immune system to recognise and attack cancer cells, increasing patients’ length and quality of life. An idiotype vaccine is personal and must be specifically made for each patient. The aim of this study is to test the effectiveness of two types of idiotypic DNA vaccine in patients with B-cell non-Hodgkin lymphoma, a type of cancer that affects white blood cells.

Who can participate?
Patients aged 18 to 75 with B-cell non-Hodgkin lymphoma

What does the study involve?
At the first assessment a standard biopsy (tissue sample) is performed – i.e. an enlarged lymph node is surgically removed. The biopsy is used for diagnosis as well as for vaccine production. After that, participants undergo standard treatment. 2-6 months after the completion of treatment, participants receive the vaccine by injection three times per month with an interval. After the whole course of vaccinations, participants visit the hospital several times (after 1 week, 1 month and 2 months) for standard tests and blood samples to test their immune response. If the first course of vaccination is not followed by an immune response, the vaccination course can be repeated with another form of the vaccine. Side effects are also recorded.

What are the possible benefits and risks of participating?
If the vaccination is successful, patients may be free of cancer symptoms (in remission) for longer. Risks of vaccination include some discomfort at the injection site for a day or two, and in rare cases weakness or fever may occur.

Where is the study run from?
1. N.N. Alexandrov National Cancer Centre of Belarus
2. Belarusian Research Center for Pediatric Oncology, Hematology and Immunology

When is the study starting and how long is it expected to run for?
April 2014 to December 2021 (updated 07/07/2021, previously: June 2019)

Who is funding the study?
Ministry of Health of the Republic of Belarus

Who is the main contact?
1. Dr Nadzeya Piatrouskaya (savitri@tut.by)
2. Dr Alexander Meleshko

Contact information

Dr Nadzeya Piatrouskaya
Scientific

N.N. Alexandrov National Cancer Centre of Belarus
Lesnoy
Minsk
223040
Belarus

Phone +375 (17)2879505
Email savitri@tut.by
Dr Alexander Meleshko
Scientific

Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
v. Borovlyani, Frunzenskaya st., 43
Minsk
223053
Belarus

ORCiD logoORCID ID 0000-0001-6964-3635

Study information

Study designNon-randomised study
Primary study designInterventional
Secondary study designNon randomised study
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the following contact details to request a participant information sheet: Nadzeya A. Piatrouskaya (savitri@tut.by)
Scientific titlePhase I clinical trial of idiotypic DNA vaccine administered as a complex with polyethylenimine to patients with B-cell lymphoma
Study acronymId-DNA/PEI vaccine
Study objectivesIn this study Id DNA vaccine delivered as a DNA/PEI complex is evaluated in patients with B-cell non-Hodgkin lymphomas. First, two versions of immunostimulatory genes are compared: potato virus X coat protein (PVXCP) and human chemokine MIP3α. Second, the synthetic polymer linear PEI complexed with DNA vaccine is applied to enhance transfection efficacy in vivo.
Ethics approval(s)National Cancer Centre of Belarus ethics committee, 17/03/2015, ref: 20142755
Health condition(s) or problem(s) studiedFollicular lymphoma, small lymphocytic lymphoma/chronic lymphocytic leukemia, mantle cell lymphoma, nodal marginal zone B cell lymphoma, MALT lymphoma, lymphoplasmacytic lymphoma, diffuse large B-cell lymphoma
InterventionAfter informed consent, patients underwent an excisional lymph node biopsy to confirm diagnosis and to provide the material for Id identification and cloning. Patients received standard therapy for their diagnosis (4-6 months), and then were not treated for 2 to 6 months for immune recovery. Once the vaccine has been prepared, the patient received one or two courses of three vaccinations monthly. One of two vaccine constructions (scFv-PVXCP or MIP3A-scFv) was used per patient. Patients receive that form of the vaccine (scFv-PVXCP or MIP3A-scFv) which was first obtained by genetic engineering, so it is a random choice. However, this is not true randomization. After the last (3rd) vaccination in the course, immune response is observed at three time points: 1 week, 1 month and 2 months. If the first course of vaccination is not followed by immune response, they may be assigned a second course of vaccination with another form of the vaccine. Minimal residual disease (MRD) monitoring and at least one Magnetic Resonance Tomography (MRT) examination are performed for half a year after the last vaccination.

One dose included 500 μg of plasmid DNA solution in 1-2 ml sterile DPBS buffer. Linear PEI 8 kDa was used to prepare complexes with plasmid DNA with a ratio of N (PEI) to P (DNA) of 10/1. The required amount of 10 μg/μl solution PEI stock solution was diluted with 5% glucose to an equal volume of DNA solution added to it and rapidly mixed by pipetting. Mixture was kept for 10 minutes at room temperature to form complexes and administrated by intramuscular injection into the gluteal muscle.

The total duration of treatment is: standard chemotherapy (4-6 months) + recovery (2-6 months) + vaccination (2 months) + follow up (2 months – immune, 6 months – MRD, end of the study - survival).
Intervention typeBiological/Vaccine
Pharmaceutical study type(s)
PhasePhase I
Drug / device / biological / vaccine name(s)
Primary outcome measureSafety and tolerability of vaccination; local and systemic adverse events are observed and symptoms are measured according to Common Terminology Criteria for Adverse Events v4.0 (CTCAE)
Secondary outcome measuresImmunologic response to vaccination (anti-Id cellular and humoral immune response), measured using ELISPOT and ELISA at diagnosis (before treatment), before vaccination (after treatment), 1 week, 1 month and 2 months after the last vaccination
Overall study start date03/04/2014
Completion date31/12/2021

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants30
Key inclusion criteria1. Surface immunoglobulin G or M isotype expression on tumor cells
2. Presence of tumor tissue biopsy before any treatment
3. The physical status scale ESOG 0 - 2
4. Life expectancy at least 24 months
5. Age 18 to 75 years
6. Adequate renal, hepatic, and bone marrow function
7. Signed written informed consent
8. The patient's ability to carry out the instructions of the doctor-researcher and comply with the treatment plan
Key exclusion criteria1. Pregnancy and lactation
2. The presence of multiple primary cancer
3. History of autoimmune diseases (except Hashimoto's thyroiditis)
4. Severe diseases, including proceeding with symptomatic, untreated inflammatory and infectious processes
5. Social, economic or geographic circumstances which impede proper compliance with treatment protocols and follow-up
6. Polysensitisation
7. Positive tests for human immunodeficiency virus (HIV), hepatitis B or C
Date of first enrolment03/04/2014
Date of final enrolment01/10/2021

Locations

Countries of recruitment

  • Belarus

Study participating centres

N.N. Alexandrov National Cancer Centre of Belarus
Lesnoy
Minsk
223040
Belarus
Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
v. Borovlyani, Frunzenskaya st., 43
Minsk
223053
Belarus

Sponsor information

Ministry of Health of the Republic of Belarus (MH RB)
Government

Ministry of Health of the Republic of Belarus
39 Myasnikova Street
Minsk
220048
Belarus

Phone +375 (17) 222-65-47
Email mzrb@belcmt.by
Website http://minzdrav.gov.by/en
ROR logo "ROR" https://ror.org/049840423

Funders

Funder type

Government

Ministry of Health of the Republic of Belarus (MH RB)

No information available

Results and Publications

Intention to publish date30/06/2022
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryData sharing statement to be made available at a later date
Publication and dissemination planAt least two articles - the first in the near future to announce the start of the clinical trial, and the second
at the end of the study, in which the immunogenicity of the vaccine and other results will be described.
IPD sharing planNot provided at time of registration

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Protocol article protocol 03/06/2017 Yes No
Results article 06/07/2022 28/07/2022 Yes No

Editorial Notes

28/07/2022: Publication reference added.
07/07/2021: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/12/2018 to 01/10/2021.
2. The overall end date was changed from 30/06/2019 to 31/12/2021.
3. The intention to publish date was changed from 30/06/2020 to 30/06/2022.
4. The plain English summary was updated to reflect these changes.
01/03/2019: Internal review.
09/03/2017: Publication reference added.