Hematology patients eligible for COVID-19 revaccination after cell therapy or B-cell-depleting immunochemotherapy Infections and Infestations
Conditions
Interventions
Observational cohort study among 250 hematology patients categorized into five different groups (n = 50 per group). All participants will receive three mRNA COVID-19 vaccination doses 4 weeks apart, f
Sponsors
Amsterdam University Medical Centers
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age =18 years Group 1: Patients who received: 1. B cell depleting immunochemotherapy (n = 50), at least 8 months after the last B-cell depleting therapy before the first vaccination 2. B cell depleting CAR T cell therapy (n = 50); 3 months after treatment Group 2: Patients who received autologous HCT for: 1. Multiple myeloma (myeloablative chemotherapy: high dose melphalan [HDM]) (n = 50); 3 months after treatment before the first vaccination 2. Non-Hodgkin or Hodgkin lymphoma (myeloablative chemotherapy: BCNU-etoposide-Ara-C-Melphalan (BEAM) or BCNU-thiotepa) (n = 50); at least 3 months after transplantation with a maximum of 6 months before the first vaccination Group 3: Patients who received allogeneic HCT (various indications) (n = 50) 3 months after transplantation
Exclusion criteria
Exclusion criteria: 1. Unwilling or unable to give informed consent 2. Known allergy to one of the components of the vaccine 3. Patients with a life expectancy of <12 months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Cellular antigen specific B and T cell responses. These will be measured with AIM (activation-induced marker) assays using flow cytometry. Humoral responses expressed in antibody concentration (BAU/ml), avidity, neutralization (expressed as ID50)) and SARS-CoV-2 specific immunity. Humoral responses will be measured by using bead-based multiplex immune assay against subunit 1 (S1), receptor binding domain (RBD), and nucleocapsid (N) antigen domains of SARS-CoV-2 determined quantitatively and centrally. Neutralization will be tested using lentiviral-based pseudoviruses expressing SARS-CoV-2 variants. Measured prior to the start of the revaccination schedule. 2. SARS-CoV-2 antibody concentrations measured using bead-based multiplex assays at 28 days after each revaccination. After the first vaccination the researchers will also measure antibody concentration 7 days after vaccination. 3. The number of revaccinations needed for each patient group to reach sufficient SARS-CoV-2 antibody concentrations (compared to average antibody concentrations obtained in healthy individuals after the primary series of 2 vaccinations followed by a booster vaccination), measured using bead-based multiplex assays at T0, T1, T2, T3, T4, T5 and T6. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Day 7 antibody concentrations correlated with pre-revaccination, and day 28 post-vaccination, cellular and humoral immunity, as a measure of residual immunity. Measured using bead-based multiplex assays. 2. Humoral and cellular immunity 28 days after each vaccination, measured using FACS analysis and bead-based multiplex assays. 3. B-cell maturation measured by avidity test/indices, (clonal) antigen-specific B cell analysis and antibody glycosylation prior to and 28 days after each vaccination. 4. The cellular immune response by cytokine production and expression of activation and exhaustion markers on CD4 and CD8 T cells prior to and 28 days after each vaccination, measured using FACS analysis. 5. Cellular and humoral SARS-CoV-2 specific immunity 5 months after the 3rd vaccination, measured using FACS analysis and bead-based multiplex assays. 6. Immune parameters (e.g. peripheral blood B and T cell numbers, IgG concentrations) associated with cellular and humoral responses to COVID-19 re-vaccination, measured by the immunological laboratory with FACS analysis. 7. Clinical parameters (e.g. hematologic diagnosis, current and past therapies including immunosuppressive drugs, date of last therapy) associated with responses to COVID-19 re-vaccination, measured using the Castor database which includes clinical parameters from patient files at all timepoints. 8. The effect of previous SARS-CoV2 infection on COVID-19 re-vaccination responses, type of measurement to be determined at later date. Will include subjects that contract COVID-19 during the study and will be studied with appropriate tests. 9. Serious adverse events (SAE) <7 days after each COVID-19 re-vaccination, reported yearly using a line listing since there are minimal risks associated with the study. They will report to the medical ethical testing committee as prescribed by the definitions of the METC. 10. SARS-CoV-2 breakthrough infection and severity (including death) after COVID-19 re-vaccination, | — |
Countries
Netherlands
Contacts
Public ContactPaul den Tex
Outcome results
None listed