Submitted April 2, 2008
Accepted June 22, 2008
Pharmacokinetics, pharmacodynamics, efficacy and safety of a new recombinant asparaginase preparation in children with previously untreated acute lymphoblastic leukemia- a randomized phase II clinical trial
Rob Pieters*, Inge Appel, Hans-Juergen Kuehnel, Iris Tetzlaff-Fohr, Uwe Pichlmeier, Inekee van der Vaart, Eline Visser, and Rolinda Stigter
Department of Pediatric Oncology and Hematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, Netherlands
medac GmbH, Hamburg, Germany
* Corresponding author; email: rob.pieters{at}erasmusmc.nl.
The pharmacokinetics, pharmacodynamics, efficacy and safety of a new recombinant E.coli-asparaginase preparation was compared to the commercially available asparaginase preparation Asparaginase medacTM. 32 children with de novo ALL were randomized to receive one of both agents at a dose of 5,000 U/m2 every 3 days for a total of 8 doses during induction treatment. The serum activity-time profile following the first dose of recombinant asparaginase was similar to that of Asparaginase medacTM. The trough serum activities observed were above the desired threshold of 100 U/L in both treatment groups. Asparagine was completely depleted in serum and in CSF for the desired time period, whereas glutamine levels were only moderately influenced. No significant difference between the two treatments regarding the degree of asparagine depletion, duration of the depletion, complete remission rate and minimal residual disease status at the end of induction treatment, overall frequency, intensity or onset of adverse events was seen. Observed adverse reactions are known as possible and labeled side effects of asparaginase treatment and chemotherapy. We conclude that the new recombinant asparaginase and other native Asparaginase medacTM are bioequivalent and have the same pharmacodynamic effects and the same direct toxicity profile in children with de novo ALL. This trial was registered at http://www.controlled-trials.com as # ISRCTN 75734403.
