The main objective of the study is to develop an optimal and individualized asparaginase treatment protocol. The study consist of four sub-studies. The objective of the population pharmacokinetic study is to get more insight in the pharmacokinetics…
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameters are clearance, inter- and intra-patient variability
in clearance and volume of distribution in the population pharmacokinetics
study, difference in intracellular MTX polyglutamate concentration and toxicity
in the MTX study, the difference in asparaginase toxicity profiles in the
toxicity study and difference in costs in the cost analysis.
Secondary outcome
Not applicable.
Background summary
Asparaginase is an essential component of combination therapy of acute
lymphoblastic leukemia in children. In order to have better insight in and
influence on asparaginase activity levels, a therapeutic drug monitoring (TDM)
program is now used to individualize asparaginase dosing schedules all patients
treated according to the DCOG ALL11 protocol. Besides, a randomized study is
now being performed to determine if a more continuous dosing schedule leads to
less hypersensitivity reactions and toxicity to asparaginase. In the
randomization study, patients in the experimental arm are treated with
asparaginase and high dose MTX concomitantly, possibly causing differences in
toxicity and efficacy of MTX. In the ALL10 protocol, asparaginase toxicity
profiles were studied and it showed, among other things, that triglyceride
levels were elevated. Our study consists of four sub-studies: 1) Population
pharmacokinetics; 2) The effect of asparaginase on methotrexate (MTX) efficacy
and toxicity; 3) The toxicity study and 4) a cost analysis.
Study objective
The main objective of the study is to develop an optimal and individualized
asparaginase treatment protocol. The study consist of four sub-studies. The
objective of the population pharmacokinetic study is to get more insight in the
pharmacokinetics of PEGasparaginase, e.g. clearance, it*s the intra- and
inter-individual variability of clearance. In the MTX study, we evaluate if
asparaginase does affect methotrexate efficacy and toxicity. In the toxicity
study, the main objective is to compare the toxicity profiles of continuous and
non-continuous PEGasparaginase therapy and to evaluate if the TDM program leads
to less toxicity. The cost analysis will evaluate if individualized dosing
results in a reduction of costs comparing to the fixed dose schedule.
Study design
The population pharmacokinetic study, the methotrexate study and the
asparaginase toxicity study will be prospective observational studies.
Study burden and risks
There is no direct benefit for the participants. Results of this study will
most likely be of importance in future asparaginase treatment for children with
cancer. The risk of these sub-studies is negligible. We will not make any
changes to standard treatment in these studies.
Wytemaweg 80
Rotterdam 3015CN
NL
Wytemaweg 80
Rotterdam 3015CN
NL
Listed location countries
Age
Inclusion criteria
- Patients who are treated according to the DCOG ALL11 protocol.
- Informed consent have to be signed by parents/guardians and patient of 12 years or older.
Exclusion criteria
- Patients who have a contraindication for asparaginase.
- Patients with hypersensitivity reactions to PEGasparaginase will switch to Erwinia asparaginase. These patients will be included in the population pharmacokinetic analysis up to the point a hypersensitivity reaction occurs. They will still remain included in the 3 other studies.
- Patients who are stratified as high risk will be excluded from the methotrexate 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
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL50250.078.14 |