Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04871165 |
| Other study ID # |
OH-VACC-IMMUN |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
March 24, 2021 |
| Est. completion date |
March 1, 2024 |
Study information
| Verified date |
December 2021 |
| Source |
Vilnius University |
| Contact |
Kazimieras Maneikis, MD |
| Phone |
+37068862381 |
| Email |
kazimieras.maneikis[@]santa.lt |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The study will evaluate the immunogenicity, safety and efficacy of vaccines against severe
acute respiratory syndrome corona virus 2 (SARS-CoV-2) in oncohematological patient
population and compare the results with patients without prior oncohematological disease. The
study is comprised of retrospective and prospective parts. In retrospective part, biobanked
residual biological patient material and data will be used. In prospective part, vaccinated
oncohematological patients and vaccinated patients without prior oncohematological disease
will be invited to participate in long-term follow-up. The subjects will be invited for blood
sample collection every three months from the second vaccine dose administration, i.e. 3
mos., 6 mos., 9 mos. etc. When the study subject receives booster dose, additional blood
samples for immunogenicity analyses will be collected up to 14 days before and 4-8 weeks
after the booster vaccine dose. The follow-up time points occurring every three months will
be counted from the last vaccine's dose. Ten time points in total will be collected and
tested for humoral and cellular immunogenicity. For safety analysis patient self-documented
systemic events (fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle
pain, and new or worsened joint pain) occurring up to 7 days following each vaccine dose will
be systematized and compared between oncohematological patients and healthy individuals. For
efficacy analysis, polymerase chain reaction assay (PCR) confirmed symptomatic disease rates,
hospitalization rates and mortality rates will be assessed.
Description:
The study will evaluate the immunogenicity, safety and efficacy of vaccines against
SARS-CoV-2 in oncohematological patient population and compare the results with patients
without prior oncohematological disease. The study is comprised of retrospective and
prospective parts. In retrospective part, biobanked residual biological patient material and
data will be used. In prospective part, vaccinated oncohematological patients and vaccinated
patients without prior oncohematological disease will be invited to participate in long-term
follow-up. The subjects will be invited for blood sample collection every three months from
the second vaccine dose administration, i.e. 3 mos., 6 mos., 9 mos. etc. When the study
subject receives booster dose, additional blood samples for immunogenicity analyses will be
collected up to 14 days before and 4-8 weeks after the booster vaccine dose. The follow-up
time points occurring every three months will be counted from the last vaccine's dose. Ten
time points in total will be collected and tested for humoral and cellular immunogenicity,
detailed below.
The study sample size is based on the number of oncohematological patient population,
eligible for vaccination. Our assumed study sample size during the whole study period is up
to 2500 adult patients + up to 200 adolescent patients with oncohematological disease and up
to 500 adult + up to 70 adolescent patients without prior oncohematological disease. The size
of the control group is aimed at achieving sufficient samples for statistical comparison of
the groups. All study participants will have received a vaccination schedule specified in
each vaccine's Summary of Product Characteristics.
For humoral immunogenicity evaluation blood serums from up to 2500 adult patients + up to 200
adolescent patients with oncohematological disease and up to 500 adult + up to 70 adolescent
patients without prior oncohematological disease will be tested at the following time points:
1) up to 10 days before the first vaccine dose, 2) on the day of second vaccine dose, 3) 1 to
3 weeks after second vaccine dose. Further samples will be obtained every 3 months after
administration of second vaccine dose. When the study subject receives booster dose,
additional blood samples for immunogenicity analyses will be collected up to 14 days before
and 4-8 weeks after the booster vaccine dose. The follow-up time points occurring every three
months will be counted from the last vaccine's dose. 10 follow-up time points in total. The
samples will be used to perform S-binding immunoglobulin G (IgG), receptor-binding domain
(RBD)-binding IgG and N-binding IgG immunoassays, SARS-CoV-2 serum neutralization assay
against different SARS-CoV-2 variants and quantitative serum immunoglobulin tests.
For cellular immunogenicity evaluation PBMC samples from up to 100 oncohematological patients
and 20 healthy individuals will be tested at the following time points: 1) up to 10 days
before the first vaccine dose and 2) 1 to 3 weeks after second vaccine dose. Further samples
will be obtained every 3 months after administration of second vaccine dose. When the study
subject receives booster dose, additional blood samples for immunogenicity analyses will be
collected up to 14 days before and 4-8 weeks after the booster vaccine dose. The follow-up
time points occurring every three months will be counted from the last vaccine's dose. Ten
follow-up time points in total. Cellular immunogenicity will be evaluated in
oncohematological patients, who may have a weak humoral response to vaccines. The following
groups of oncohematological patients will be included: 1) 20 to 40 recent recipients of
allogeneic stem cell transplantation (allo-SCT), meeting these requirements: 2-8 months after
allo-SCT; cluster of differentiation 3 (CD3) positive cell count >0.1*109/L; patients with
mild chronic graft-versus-host disease (GvHD) and/or receiving <0.5mg/kg prednisolone (or
equivalent); patients with <2nd grade acute GvHD; >3 months after anti-CD20 therapy;
postgraft immunosuppression with calcineurin inhibitors is allowed; 2) 20 to 40 patients
after recent administration of proteasome inhibitors (0-30 days after treatment), who
received at least one full cycle of treatment and achieved a satisfactory and stable disease
response, allowing a safe temporary treatment discontinuation for immunization against
COVID-19; 3) 20 to 40 patients after a recent anti-CD20 administration (0-180 days after
treatment), who received at least one full cycle of treatment and achieved satisfactory and
stable disease response, allowing a safe temporary treatment discontinuation for immunization
against COVID-19. Other specific patient groups will be enrolled in the cellular
immunogenicity part, as the primary analysis results show which specific subpopulations lack
humoral immune response. PBMC samples from individuals without prior diagnosis of
oncohematological disease will be selected randomly. The samples will be used for assessment
of proinflammatory cytokine (interferon-gamma (IFN-gamma), interleukin-2 (IL-2) and IL-4)
production and immunophenotypic analysis (CD45, CD3, CD4, CD8, CD16, CD56, CD14, CD19) after
stimulation with overlapping S-peptides in PBMC.
Cellular immunogenicity will be evaluated by performing quantitative sequencing for T-cell
receptor (TCR) repertoires for SARS-CoV-2-specific antigens using immunoSEQ technology
(Adaptive Biotechnologies Inc., 1165 Eastlake Ave E, Seattle, Washington 98109, United
States).
For safety analysis patient self-documented systemic events (fever, fatigue, headache,
chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain)
occurring up to 7 days following each vaccine dose will be systematized and compared between
oncohematological patients and healthy individuals.
For efficacy analysis, PCR confirmed symptomatic disease rates, hospitalization rates and
mortality rates will be assessed. In case of detected breakthrough infection, additional
biological samples will be obtained as soon as possible to evaluate humoral and cellular
immunity at the time of infection and repeated until PCR-negativity is achieved.
