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
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
Scientific
N.N. Alexandrov National Cancer Centre of Belarus
Lesnoy
Minsk
223040
Belarus
| Phone | +375 (17)2879505 |
|---|---|
| savitri@tut.by |
Scientific
Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
v. Borovlyani, Frunzenskaya st., 43
Minsk
223053
Belarus
 ORCID ID |
0000-0001-6964-3635 |
|---|
Study information
| Study design | Non-randomised study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| 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 title | Phase I clinical trial of idiotypic DNA vaccine administered as a complex with polyethylenimine to patients with B-cell lymphoma |
| Study acronym | Id-DNA/PEI vaccine |
| Study objectives | In 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) studied | Follicular 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 |
| Intervention | After 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 type | Biological/Vaccine |
| Pharmaceutical study type(s) | |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | |
| Primary outcome measure | Safety 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 measures | Immunologic 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 date | 03/04/2014 |
| Completion date | 31/12/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 30 |
| Key inclusion criteria | 1. 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 criteria | 1. 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 enrolment | 03/04/2014 |
| Date of final enrolment | 01/10/2021 |
Locations
Countries of recruitment
- Belarus
Study participating centres
Minsk
223040
Belarus
Minsk
223053
Belarus
Sponsor information
Government
Ministry of Health of the Republic of Belarus
39 Myasnikova Street
Minsk
220048
Belarus
| Phone | +375 (17) 222-65-47 |
|---|---|
| mzrb@belcmt.by | |
| Website | http://minzdrav.gov.by/en |
"ROR" |
https://ror.org/049840423 |
Funders
Funder type
Government
No information available
Results and Publications
| Intention to publish date | 30/06/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | At 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 plan | Not 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.
