To investigate what the ideal moment to vaccinate would be, early (after 2-6 months) or late (after 9-12 months) after cessation of rituximab. Secondly to study the immune-response to vaccination with influenza virus vaccine after treatment with…
ID
Source
Brief title
Condition
- Viral infectious disorders
- Lymphomas non-Hodgkin's B-cell
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Immune response to vaccination in patients who were treated with rituximab, in
association with the reconstitution of immune function. Parameters are:
• Antibody titres the influenza virus vaccine before and after vaccination.
Secondary outcome
• Immunoglobulin levels and subclass.
• Lymphocyte subsets (number of B cells and memory-B cells, CD3, CD4, CD8 and
NK cells).
• Production of IFN-* by CD4+ cells. This will be measured in order to
investigate if cellular mediated immune responses are intact after rituximab
treatment.
• Cytokines and genetic factors (for example BAFF, CXCL13, APRIL) influencing B
cell development and survival will be measured in order to determine if there
is a correlation between specific cytokines/genetic factors and the observed
B-cell depletion/reconstitution.
• Serum rituximab levels.
• The relationship between time after last dose, number of doses of rituximab
and chemotherapy and increase in antibody titres. At what time point after
rituximab adequate antibody titres can be generated.
Background summary
Rituximab is a chimeric anti-CD20 monoclonal antibody used in combination with
chemotherapy for the treatment of non-Hodgkin*s lymphoma (NHL). Following
infusion with rituximab, B-cell depletion in the peripheral blood occurs within
days. Levels of normal peripheral B-cells remain low for 2-6 months. Because of
the immunosuppressive (chemo) therapy, patients might be prone to develop
infections with the influenza virus. Vaccination against this virus is,
therefore, indicated for these immunocompromised patients. However little is
known about the effect of rituximab with chemotherapy in patients with
non-Hodgkin lymphoma on the response to vaccination.
Study objective
To investigate what the ideal moment to vaccinate would be, early (after 2-6
months) or late (after 9-12 months) after cessation of rituximab. Secondly to
study the immune-response to vaccination with influenza virus vaccine after
treatment with rituximab in relation to the reconstitution of immune-function
(in terms of number of B-cells, lymphocyte subsets, immunoglobulin levels and
IgG subclasses, CD4+ IFN-* production, BAFF, CXCl13 and IL-10).
Study design
The design is a cohort study with a control group. A total of hundred-twenty
(120) patients with non-Hodgkin*s lymphoma, who were treated with rituximab in
the last twelve months before start of the study and are in remission, will be
included. Patients will be divided in 2 groups: the first group will consist of
patients who received the last dose of rituximab 3-6 months ago (= early
group), the second group consists of patients who received rituximab 9-12
months ago (= late group). The control group will not be included in the
analysis in order to define which moment is the best to vaccinate patients. The
control group is initiated in order to serve as a reference of immune
components who are measured to be able to investigate the secondary objective.
The control group will consist of 40 age, sex and morbidity matched controls
who are recruted atthe general practioner.
Intervention
All patients and controls will receive the influenza virus vaccine Influvac®.
The vaccine will be used in the authorised form according to existing
vaccination protocols for immunocompromised patients. At three different
timepoints sera will be taken and investigated. From healthy controls sera will
be taken twice.
Study burden and risks
Patients will be vaccinated with the influenza vaccine at the dutch annual
vaccination campaign according to existing vaccination protocols in immune
compromised patients. Blood samples will be drawn before vaccination and three
weeks after and six months after vaccination, so three blood samples will be
drawn. If possible, vaccination will be integrated in normal out-patient
clinical visits. The vaccine will be used in the authorised form and for their
authorised purpose, therefore no additional risks are to be expected. Patient
discomfort might consist of a painful arm/leg after vaccination. Adverse events
which are common (0.1-1%) include headache, fever, myalgia, artralgia, nausea,
vomiting, and pain and redness at the vaccination spot. Rare events are
allergic reactions (very rare leading to shock), angio edema, neurologic
disorders and urticaria. Benefit is protection against infection with the
influenza virus.
Koekoekslaan 1
Nieuwegein 3435 CM
NL
Koekoekslaan 1
Nieuwegein 3435 CM
NL
Listed location countries
Age
Inclusion criteria
1. Patients with non-Hodgkin*s lymphoma, treated with rituximab (with a range of 6-12 cycles) and who are in remission.
2. Completion of rituximab therapy in the last twelve months before start of the study.
3. Age >= 18 years.
4. Signing of informed consent.;Controls:
1. Age, sex and co-morbidity matched controls
Exclusion criteria
1. Completion of rituximab therapy 7-8 months before start of the study.
2. Fever at time of vaccination.
3. Previous/known allergic reaction to any of the components of the vaccines given.;Controls:
1. Immunocompromised persons will be excluded (for example immunosuppressive medication).
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
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-002932-24-NL |
| CCMO | NL37320.100.11 |
| Other | NTR3155, NCT01707628 |
| OMON | NL-OMON23415 |