Condition category
Cancer
Date applied
12/11/2016
Date assigned
24/11/2016
Last edited
09/03/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

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 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

Trial website

Contact information

Type

Scientific

Primary contact

Dr Nadzeya Piatrouskaya

ORCID ID

Contact details

N.N. Alexandrov National Cancer Centre of Belarus
Lesnoy
Minsk
223040
Belarus
+375 (17)2879505
savitri@tut.by

Type

Scientific

Additional contact

Dr Alexander Meleshko

ORCID ID

http://orcid.org/0000-0001-6964-3635

Contact details

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

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

Protocol reg.# 20142755

Study information

Scientific title

Phase I clinical trial of idiotypic DNA vaccine administered as a complex with polyethylenimine to patients with B-cell lymphoma

Acronym

Id-DNA/PEI vaccine

Study hypothesis

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

National Cancer Centre of Belarus ethics committee, 17/03/2015, ref: 20142755

Study design

Non-randomised study

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient 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)

Condition

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

Phase

Drug names

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 trial start date

03/04/2014

Overall trial end date

30/06/2019

Reason abandoned (if study stopped)

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

30

Participant 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

Recruitment start date

03/04/2014

Recruitment end date

31/12/2018

Locations

Countries of recruitment

Belarus

Trial participating centre

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

Trial participating centre

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

Sponsor information

Organisation

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

Sponsor details

Ministry of Health of the Republic of Belarus
39 Myasnikova Street
Minsk
220048
Belarus
+375 (17) 222-65-47
mzrb@belcmt.by

Sponsor type

Government

Website

http://minzdrav.gov.by/en

Funders

Funder type

Government

Funder name

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

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

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.

Intention to publish date

30/06/2020

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

2017 protocol in: https://www.ncbi.nlm.nih.gov/pubmed/28272989

Publication citations

Additional files

Editorial Notes

09/03/2017: Publication reference added.