Inge M van der Sluis1,2, Hester de Groot-Kruseman3, Maroeska Te Loo4, Wim J E Tissing5, Cor van den Bos6, Gertjan J L Kaspers1,7, Marc Bierings1,8, Wouter J W Kollen1,9, Thorsten König10, Uwe Pichlmeier10, Hans-Jürgen Kühnel10, Rob Pieters1. 1. Department of Hemato-oncology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands. 2. Department of Pediatric Oncology and Hematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands. 3. Dutch Childhood Oncology Group, The Hague, The Netherlands. 4. Department of Pediatric Hemato-oncology, University Medical Center St. Radboud, Nijmegen, The Netherlands. 5. Pediatric Oncology/Hematology, University Medical Centre Beatrix Children's Hospital, Groningen, The Netherlands. 6. Department of Pediatric Oncology, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands. 7. Department of Pediatric Oncology/Hematology, VU University Medical Centre, Amsterdam, The Netherlands. 8. Wilhelmina Children's Hospital, University Medical Centre, Utrecht, The Netherlands. 9. University Medical Centre Leiden, Leiden, The Netherlands. 10. medac GmbH, Wedel, Germany.
Abstract
BACKGROUND: The efficacy and safety of recombinant Escherichia coli-asparaginase (rASNase) was compared to native E.coli asparaginase (Asparaginase medac). METHODS:One hundred and ninety-nine children with newly diagnosed acute lymphoblastic leukemia were randomized to receive one of both agents at a dose of 5,000 U/m² during induction (eight doses) and 10,000 U/m² during the postinduction phase (only high-risk patients; standard- and medium-risk patients received pegaspargase). RESULTS:Median trough serum asparaginase activity levels were comparable between both groups; they ranged from 143 to 182 U/l during induction and were above the target value of 100 U/l. Complete asparagine depletion in serum was achieved in 97.9% of patients, with no significant differences between both groups. On day 33 (end of induction), only two (2%) evaluable patients in each group had measurable asparagine serum levels, and complete asparagine depletion in the cerebrospinal fluid was achieved in 98.8% and 93.6% of the patients with rASNase and Asparaginase medac, respectively. During induction, 2.1% and 5% of patients developed an allergic reaction to rASNase or Asparaginase medac, respectively. Approximately 41% of the patients in both groups had a clinical allergy or enzyme inactivation to the first dose of any asparaginase preparation in postinduction. A comparable proportion of patients in both groups developed anti-asparaginase antibodies (57%) during repeated administration of asparaginase. Minimal residual disease levels at the end of induction, 5-year event-free survival, and 5-year cumulative incidence of relapse did not differ between both groups. CONCLUSION: The efficacy, safety, and immunogenicity of both asparaginase preparations are comparable. This trial was registered at www.clinicaltrials.gov as #NCT00784017; EudraCTnumber 2006-003180-31.
RCT Entities:
BACKGROUND: The efficacy and safety of recombinant Escherichia coli-asparaginase (rASNase) was compared to native E.coli asparaginase (Asparaginase medac). METHODS: One hundred and ninety-nine children with newly diagnosed acute lymphoblastic leukemia were randomized to receive one of both agents at a dose of 5,000 U/m² during induction (eight doses) and 10,000 U/m² during the postinduction phase (only high-risk patients; standard- and medium-risk patients received pegaspargase). RESULTS: Median trough serum asparaginase activity levels were comparable between both groups; they ranged from 143 to 182 U/l during induction and were above the target value of 100 U/l. Complete asparagine depletion in serum was achieved in 97.9% of patients, with no significant differences between both groups. On day 33 (end of induction), only two (2%) evaluable patients in each group had measurable asparagine serum levels, and complete asparagine depletion in the cerebrospinal fluid was achieved in 98.8% and 93.6% of the patients with rASNase and Asparaginase medac, respectively. During induction, 2.1% and 5% of patients developed an allergic reaction to rASNase or Asparaginase medac, respectively. Approximately 41% of the patients in both groups had a clinical allergy or enzyme inactivation to the first dose of any asparaginase preparation in postinduction. A comparable proportion of patients in both groups developed anti-asparaginase antibodies (57%) during repeated administration of asparaginase. Minimal residual disease levels at the end of induction, 5-year event-free survival, and 5-year cumulative incidence of relapse did not differ between both groups. CONCLUSION: The efficacy, safety, and immunogenicity of both asparaginase preparations are comparable. This trial was registered at www.clinicaltrials.gov as #NCT00784017; EudraCT number 2006-003180-31.
Authors: Carmelo Rizzari; Claudia Lanvers-Kaminsky; Maria Grazia Valsecchi; Andrea Ballerini; Cristina Matteo; Joachim Gerss; Gudrun Wuerthwein; Daniela Silvestri; Antonella Colombini; Valentino Conter; Andrea Biondi; Martin Schrappe; Anja Moericke; Martin Zimmermann; Arend von Stackelberg; Christin Linderkamp; Michael C Frühwald; Sabine Legien; Andishe Attarbaschi; Bettina Reismüller; David Kasper; Petr Smisek; Jan Stary; Luciana Vinti; Elena Barisone; Rosanna Parasole; Concetta Micalizzi; Massimo Zucchetti; Joachim Boos Journal: Haematologica Date: 2019-01-31 Impact factor: 9.941