Clinical trial NCT00819351: ALL2008 Protocol for Childhood Acute Lymphoblastic Leukemia Intermittent Versus Continuous PEG Asparaginase
Official title: NOPHO Treatment Protocol for Children (1.0 - 17.9 Years of Age) and Young Adults(18.0-45.0 Years) With Acute Lymphoblastic Leukemia. Intermittent Versus Continuous PEG-asparaginase for Asparagine Depletion
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Lymphoblastic Leukemia
Keywords: acute lymphoblastic leukemia
child
PEG-Asparaginase
EFS
efficacy
childhood acute lymphoblastic leukemia
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Nordic Society for Pediatric Hematology and Oncology
First posted: 2009-01-09
Enrollment: 650
Sex: ALL
Minimum age (years): 1
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate if intramuscular PEG-asparaginase administered either at six or two week intervals from day 92 until 8 months from diagnosis for patients with non-HR ALL will result in equal probability of Event Free Survival

Detailed description: 20% of children with ALL still fails to be cured. The ALL-2008 protocol is a treatment and research protocol that aims to improve the overall outcome of Nordic children and adolescents with ALL in comparison with the ALL-2000 protocol and previous NOPHO protocols.

The specific and primary objectives of the randomised study is:

To test if intramuscular PEG-asparaginase administered either at six or two week intervals from day 92 until 8 months from diagnosis for patients with non-HR ALL will result in equal probability of EFS. As secondary endpoints asparaginase antibody production and toxicity including allergic reactions in the treatment-arms will be analysed

Eligibility criteria: Inclusion Criteria:

* Childhood ALL
* All mandatory biological data are available6
* Written informed consent has been obtained

Exclusion Criteria:

* Bilineage ALL
* Pre-treatment with glucocorticosteroids or other antileukemic agents for more than 1 week
* ALL predisposition syndromes
* Previous cancer
* Off protocol administration of additional chemotherapy during induction therapy
* Sexually active females not using contraception
* No allergic reactions to PEG Asparaginase

Primary outcomes:
measure: Event Free Survival
timeFrame: 6 years
Secondary outcomes:
measure: Secondary Outcome Measures are toxicity (special focus on thrombosis, pancreatitis, and allergic reactions), the formation of silent antibodies, and the influence of antibody production on the EFS.
timeFrame: 6 years
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Department of Pediatrics, Rigshospitalet
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Reykjavik
country: Iceland
facility: University Hospital Reykjavik, Iceland
city: Trondheim
country: Norway
facility: Trondheim University Hospital
city: Gothenburg
country: Sweden
facility: Department of Pediatrics, Drottning Sylvias Pediatric Hospital
city: Stockholm
country: Sweden
facility: NOPHO nordic organisation for pediatric onology
Study officials:
affiliation: Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen
name: Kjeld Schmiegelow, M.D.
role: STUDY_CHAIR
References:
citation: Albertsen BK, Grell K, Abrahamsson J, Lund B, Vettenranta K, Jonsson OG, Frandsen TL, Wolthers BO, Heyman M, Schmiegelow K. Intermittent Versus Continuous PEG-Asparaginase to Reduce Asparaginase-Associated Toxicities: A NOPHO ALL2008 Randomized Study. J Clin Oncol. 2019 Jul 1;37(19):1638-1646. doi: 10.1200/JCO.18.01877. Epub 2019 Apr 12.
citation: Tram Henriksen L, Gottschalk Hojfeldt S, Schmiegelow K, Frandsen TL, Skov Wehner P, Schroder H, Klug Albertsen B; Nordic Society of Pediatric Hematology and Oncology, NOPHO Group. Prolonged first-line PEG-asparaginase treatment in pediatric acute lymphoblastic leukemia in the NOPHO ALL2008 protocol-Pharmacokinetics and antibody formation. Pediatr Blood Cancer. 2017 Dec;64(12). doi: 10.1002/pbc.26686. Epub 2017 Jun 29.
citation: Nielsen SN, Grell K, Nersting J, Abrahamsson J, Lund B, Kanerva J, Jonsson OG, Vaitkeviciene G, Pruunsild K, Hjalgrim LL, Schmiegelow K. DNA-thioguanine nucleotide concentration and relapse-free survival during maintenance therapy of childhood acute lymphoblastic leukaemia (NOPHO ALL2008): a prospective substudy of a phase 3 trial. Lancet Oncol. 2017 Apr;18(4):515-524. doi: 10.1016/S1470-2045(17)30154-7. Epub 2017 Mar 1.
citation: Wolthers BO, Frandsen TL, Abrahamsson J, Albertsen BK, Helt LR, Heyman M, Jonsson OG, Korgvee LT, Lund B, Raja RA, Rasmussen KK, Taskinen M, Tulstrup M, Vaitkeviciene GE, Yadav R, Gupta R, Schmiegelow K. Asparaginase-associated pancreatitis: a study on phenotype and genotype in the NOPHO ALL2008 protocol. Leukemia. 2017 Feb;31(2):325-332. doi: 10.1038/leu.2016.203. Epub 2016 Jul 25.
citation: Henriksen LT, Harila-Saari A, Ruud E, Abrahamsson J, Pruunsild K, Vaitkeviciene G, Jonsson OG, Schmiegelow K, Heyman M, Schroder H, Albertsen BK; Nordic Society of Paediatric Haematology and Oncology (NOPHO) group. PEG-asparaginase allergy in children with acute lymphoblastic leukemia in the NOPHO ALL2008 protocol. Pediatr Blood Cancer. 2015 Mar;62(3):427-33. doi: 10.1002/pbc.25319. Epub 2014 Nov 21.
citation: Raja RA, Schmiegelow K, Albertsen BK, Prunsild K, Zeller B, Vaitkeviciene G, Abrahamsson J, Heyman M, Taskinen M, Harila-Saari A, Kanerva J, Frandsen TL; Nordic Society of Paediatric Haematology and Oncology (NOPHO) group. Asparaginase-associated pancreatitis in children with acute lymphoblastic leukaemia in the NOPHO ALL2008 protocol. Br J Haematol. 2014 Apr;165(1):126-33. doi: 10.1111/bjh.12733. Epub 2014 Jan 15.