3.2.1 Primary objectivesTo assess the efficacy in terms of Anti-SARS-COV-2 RBD antibody responses in patients diagnosed with and/or under treatment for a hematological disorder to SARS-CoV-2 vaccination.3.2.2 Secondary objectives 1. What is theā¦
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Brief title
Condition
- Haematological disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
3.6.1 primary endpoints
Presence of Anti-SARS-CoV-2 S-protein specific antibodies one month after
vaccination (yes/no) of hematological patients that were seronegative for these
antibodies before vaccination.
Secondary outcome
3.6.2 secondary endpoints
* Titers of anti- SARS-CoV-2 S protein specific antibodies in AU/ml
pre-vaccination and 1, 3 and 6 months post-vaccination.
* Presence and percentage of SARS-CoV-2 S protein specific peptide-activated
CD8 and CD4 cells pre-vaccination and 1 and 6 months post-vaccination. This
will only be analyzed in a subpopulation of patients that did not develop any
SARS-CoV-2 S specific antibodies. In addition, a disease and treatment matched
control group that did show an antibody response will be tested for SARS-CoV-2
specific T cell responses.
* Incident of SAE < 7 days after vaccination
* Incident of SUSARs < 12 months after vaccination
* Incident of severe COVID-19 infection within 12 months after vaccination,
defined by hospitalization and/or death due to COVID-19 and positive SARS-CoV-2
PCR. Clinical severity will be scored according to the Chinese Clinical
Guidance for COVID-19 Pneumonia Diagnosis and Treatment (7th edition)
o Mild: mild symptoms, without pneumonia on chest radiology
o Moderate: fever and respiratory symptoms, with pneumonia on chest radiology
o Severe: Shortness of breath, respiratory rate * 30 times/min, Oxygen
saturation * 93% in rest, aveolar oxygen partial pressure/fraction of
inspiration O2 (PaO2/FiO2) * 300 mmHg or Pulmonary imaging showing significant
progression >50% within 24-48 hours.
o Critically ill: Respiratory failure requiring mechanical ventilation, shock
or patients combined with other organ failure in need of ICU monitoring or
treatment
Background summary
The current phase III SARS-CoV-2 vaccination studies show promising results
with high protection against COVID-19 and even higher numbers of subjects that
develop immune responses to the vaccine. However, in all of these studies only
healthy subjects were included. Hematological patients who often suffer from
malignantly transformed immune cells and who are treated with immune depleting
or immune suppressive treatment show altered immune responses to infections and
vaccination. How this vulnerable patient category will respond to SARS-CoV-2
vaccination is unknown. This question however, is very relevant since
SARS-CoV-2 infected hematological patients with malignant or premalignant
diseases are less able to clear the SARS-CoV-2 virus when infected.
The Dutch SARS-CoV-2 vaccination program is arranged in such a way, that all
patients will be vaccinated, independent of their current or previous
treatment. The program will therefor provide us with an exceptional
possibility to study the effect of different hematological diseases and
different hematological treatment modalities to the effects of SARS-CoV-2
vaccination. It will be of extraordinary value, to know whether this patient
category is protected from SARS-CoV-2 infection by the vaccination in order to
inform these patients correctly. This is a unique chance to evaluate the
capacity of the often-hampered immune system of haematological patients to
viral vaccination. Results will provide insights into the immune function of
haematological patients, which in future could also possibly translate to new
hypothesis in anticancer immunotherapy.
In this study we aim to assess multiple aspects of the immune response to
SARS-CoV-2 vaccination in patients with a hematological disease and their
treatment. We hypothesize that a small part of hematologic patients will have
an altered, attenuated or absent immune response to SARS-CoV-2 vaccines,
however we expect the majority of hematological patients to be protected from
symptomatic COVID-19.
Study objective
3.2.1 Primary objectives
To assess the efficacy in terms of Anti-SARS-COV-2 RBD antibody responses in
patients diagnosed with and/or under treatment for a hematological disorder to
SARS-CoV-2 vaccination.
3.2.2 Secondary objectives
1. What is the efficacy in terms of magnitude (level of antibody titers) of
Anti-SARS-COV-2 RBD antibody responses in patients diagnosed with and/or
treated for a hematological disorder to SARS-CoV-2 vaccination?
2. What is the efficacy in terms of SARS-COV-2 cellular immune responses in
patients diagnosed with and/or treated for a hematological disorder to
SARS-CoV-2 vaccination?
3. What is the cumulative incidence of severe COVID-19 in the year after
SARS-CoV-2 vaccination in patients diagnosed with and/or treated for a
hematological disorder?
4. Is there a correlation between the quality of cellular (T cell response) and
humoral (antibody titers) immune responses after vaccination in hematological
patients?
5. Is the quality of cellular and humoral immune responses induced by the
SARS-Cov-2 vaccine associated with the risk of symptomatic COVID-19
post-vaccination in hematological patients?
6. Is there a relationship between pre-vaccination immune status on humoral and
cellular immune responses after vaccination in hematological patients? (To
identify markers predictive for responses to SARS-CoV-2 vaccination)
7. Is there a relationship between hematological diagnosis and quality of
cellular and/or humoral immune responses after SARS-CoV-2 vaccination?
8. Is there a relationship between recent or current (within 6 months of
vaccination) chemotherapeutic, immunotherapeutic and immunosuppressive
treatment and quality of cellular and/or humoral immune responses after
SARS-CoV-2 vaccination in hematological patients?
9. What time point after hematological treatment (for the different treatment
regimens) is best, in terms of SARS-CoV-2 antibody and specific T cell
responses, to receive SARS-CoV-2 vaccination?
10. What is the persistence of SARS-CoV-2 antibody and specific T cell
responses in hematological patients after SARS-CoV-2 vaccination?
11. Evaluation of safety of the vaccine in the given patient population.
Study design
This study is a multicenter prospective observational cohort study, to
longitudinally evaluate the immunological effect, both humoral and cellular,
and protective capacity of SARS-Cov-2 vaccination in hematological patients.
Study burden and risks
We applied the risk classification as outlined in the document
*Kwaliteitsborging mensgebonden onderzoek 2.0*, formulated by the NFU
(Nederlandse Federatie van Universitair Medische Centra).
For this study, we have classified the risk negligible *verwaarloosbaar*. This
is based on the fact that no additional medical action is needed. Four tubes of
blood are drawn in addition to blood that is drawn for routine clinical care.
The total extra amount of blood per time point; 40 ml is also very small and
therefor safe, without causing harm.
Though not being a subject of investigation as of yet, we do not expect the
SARS-CoV-2 vaccination to be of higher risk of SAE nor SUSAR*s in hematological
patients as compared to healthy individuals. The mode of action of the vaccine
is identical in both patient populations. Also other vaccination strategies
(excluding vaccinations with living organisms or attenuated organisms) for
different pathogens do not show an increased risk in hematological patients.
Also the societal risk is negligible as there is much need for information and
research in COVID-19.
P.debyelaan 25
Maastricht 6229 HX
NL
P.debyelaan 25
Maastricht 6229 HX
NL
Listed location countries
Age
Inclusion criteria
all of the following
criteria:
* Currently treated, previously treated and non-treated patients
diagnosed with the hematological malignancy multiple myeloma (including MGUS)
chronic lymphocytic leukemia and non-Hodgkin lymphoma.
Previously treated patient; is defined as: treatment <; 6 months before
vaccination in patients that obtained a complete remission. Exceptions (no time
restriction for last treatment) are patients with palliative treatment for
ongoing haematological malignancies and patients after autologous and
allogeneic stem cell transplantation.
* Patients who are scheduled for and will undergo SARS-CoV-2
vaccination.
* Aged * 18 years.
* Written informed consent.
* Inclusion is irrespective of previously proven or possible (based on
symptoms) COVID-19
Exclusion criteria
excluded from participation in this study:
* Patients previously vaccinated for SARS-CoV-2.
* Patients who have senile dementia, mental impairment or any other psychiatric
disorder that prohibits the patient from understanding and giving informed
consent.
* Any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
EudraCT | EUCTR2021-001107-33-NL |
CCMO | NL76863.068.21 |