Comparative pharmacokinetics, pharmacodynamics, efficacy and safety of two asparaginase preparations in children with previously untreated acute lymphoblastic leukaemia (ALL)

ISRCTN	ISRCTN75734403
DOI	https://doi.org/10.1186/ISRCTN75734403
Protocol serial number	NTR402
Sponsor	Medac GmbH (Germany)
Funder	Not provided at time of registration

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Prof Rob Pieters
Scientific

Erasmus MC-Sophia Children's Hospital Rotterdam
Dutch Childhood Oncology Group
Pediatric Oncology
P.O. Box 2060
Rotterdam
3015 GJ
Netherlands

Phone	+31 (0)10 4636691
Email	rob.pieters@erasmusmc.nl

Primary study design	Interventional
Study design	Single centre, randomised, double-blind, parallel-group, phase II study
Secondary study design	Randomised controlled trial
Scientific title
Study objectives	Comparison of pharmacokinetics, pharmacodynamics, efficacy and safety of recombinant asparaginase (ASNase) versus asparaginase medac during induction treatment in children with de novo acute lymphoblastic leukaemia (ALL) and to demonstrate that any clinical important difference to the disadvantage of recombinant ASNase is unlikely.
Ethics approval(s)	Ethics approval received from the local medical ethics committee
Health condition(s) or problem(s) studied	Acute lymphoblastic leukaemia (ALL)
Intervention	Recombinant ASNase instead of regular ASNase Medac during induction therapy.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Recombinant asparaginase
Primary outcome measure(s)	To determine the ratio of the population geometric means of the 72 hour serum concentration versus time curves (AUC) for the first administration of recombinant asparaginase versus asparaginase medac.
Key secondary outcome measure(s)	1. Trough levels of ASNase activity in serum during subsequent ASNase infusions 2. Serum and cerebrospinal fluid (CSF) levels of asparagine, aspartic acid, glutamine, glutamic acid 3. Complete remission (CR) rate and minimal residual disease (MRD) status at day 33 4. Adverse events
Completion date	01/11/2006

Participant type(s)	Patient
Age group	Child
Lower age limit	1 Year
Upper age limit	18 Years
Sex	All
Target sample size at registration	32
Key inclusion criteria	1. Previously untreated ALL 2. Morphological proof of ALL; bone marrow greater than 25% blasts 3. Aged 1 - 18 years 4. Informed consent
Key exclusion criteria	1. Known allergy to ASNase 2. General health status according to Karnofsky/Lansky less than 40% 3. Pre-existing coagulopathy (e.g. haemophilia) 4. Pre-existing pancreatitis 5. Kidney insufficiency (creatinine greater than 220 umol/l) 6. Liver insufficiency (bilirubin greater than 50 umol/l; aspartate aminotransferase [ASAT] and alanine aminotransferase [ALAT] greater than 5 x upper limit of normal 7. Other current malignancies 8. Pregnancy, breast feeding 9. Patients suffering from mental disorders
Date of first enrolment	01/11/2004
Date of final enrolment	01/11/2006

Erasmus MC-Sophia Children's Hospital Rotterdam

Rotterdam
3015 GJ
Netherlands

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	Results	15/12/2008		Yes	No