To assess the PK/PD relationship of prednisolone as either prophylaxis or therapy of GVHD in children after HCT.
ID
Source
Brief title
Condition
- Immunodeficiency syndromes
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
PK parameters of prednisolone as either prophylaxis or therapy of GVHD in
children after HCT will be assessed, even as other determinants for development
of a population PK model using non-linear mixed effect modelling NON-MEM.
Secondary outcome
Exposure to prednisolone as measured by area-under-the-curve (AUC), maximum
concentration (Cmax) or time-above-threshold will be related to treatment
outcome. Treatment outcome is defined as occurrence and grade of GVHD in case
of prophylactic therapy and defined as the need for escalation of therapy for
treatment of GVHD. Biomarkers will be assessed using cell (mostly
flowcytometry) and protein (Luminex and Olink) assays.
Background summary
One of the biggest obstacles in hematopoietic cell transplantation (HCT)
remains the devel-opment of graft-versus-host disease (GVHD), which occurs in
approximately 40% of stem cell recipients. First-line treatment to either
prevent or treat GVHD is high dose systemic cor-ticosteroids. However, the
incidence of the development of GVHD in children receiving corti-costeroids as
prophylactic treatment is still high. Besides, only a minority of the patients
de-veloping GVHD responds adequately to corticosteroid treatment, often with
lifelong therapy and reduced quality of life. Overall mortality after
developing GVHD is around 30%. In current clinical practice, corticosteroid
dosing is highly empirical and might result in very variable exposure levels in
children. We hypothesize that precision dosing of corticosteroids, to reach an
optimal exposure in every individual patient, will increase response rates in
pediatric HCT. A pharmacokinetic/pharmacodynamic (PK/PD) relationship of
corticosteroids has been suggested in other diseases where exposure to
corticosteroids is associated with clinical out-comes. To date, this has not
yet been investigated in the setting of GVHD. As a first step to optimize
therapy for GVHD, we will study the PK/PD relationship of prednisolone in
pediatric patients. If such a relationship exists, optimal dosing strategies
can be developed.
Study objective
To assess the PK/PD relationship of prednisolone as either prophylaxis or
therapy of GVHD in children after HCT.
Study design
Prospective observational study.
Study burden and risks
Patients will not have direct benefit from participating in this study. The
data obtained in this study will be used to assess the population PK and PD of
prednisolone in children after HCT. Burden will be minimal since for
pharmacokinetics 4 to 5 (additional to SOC) blood samples of 2 ml once or twice
will be drawn (limited sampling strategy) and any samples possible of 9 ml to
study biomarkers (maximum of 8 samples, PMC only). The volume of blood that is
drawn for the study does not exceed the recommended maximum. The applied
sampling strategy is minimally invasive, since all the patients that are
included already have a central line or a venous access to draw blood for SOC.
Sampling will only be requested during hospitalization or during routine
outpatient clinic visits after HCT and/or development of GVHD.
Heidelberglaan 25
Utrecht 3584 CS
NL
Heidelberglaan 25
Utrecht 3584 CS
NL
Listed location countries
Age
Inclusion criteria
Patients treated by the PMC or LUMC;
Planned to receive systemic corticosteroids after HCT;
Informed consent form (ICF) signed prior to participation in the study;
A present central line to sample blood
Exclusion criteria
None in advance. However, according to expert opinion of the PI, any
disease/circumstance that may influence the participation of the potential
subject in a negative way, will be excluded from participation in this study
Design
Recruitment
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 |
|---|---|
| CCMO | NL70886.041.19 |
| Other | NL8703 (via ICTRP) |