Clinical trial NCT03987542: Outcome Following Truncation of Asparaginase
Official title: Outcome Following Truncation of Asparaginase in the NOPHO ALL2008 Protocol
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Relapse Leukemia
Keywords: Acute lymphoblastic leukemia
Asparaginase
Truncation
Toxicitities
Lead sponsor: Aarhus University Hospital
Sponsor class: OTHER
First posted: 2019-06-17
Enrollment: 1401
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: PROBABILITY_SAMPLE
Study population: Children aged 1-17.9 years at time of diagnosis.

Brief summary: This study aimed to investigate the outcome of patients who had their asparaginase treatment truncated in the NOPHO ALL2008 protocol.

Detailed description: Overall survival for children with ALL is now above 90% in several protocols, but asparaginase associated toxicities still constitutes a significant problem as they, besides causing acute morbidity and mortality, can cause truncation of treatment with a subsequent increased risk of relapse.

The most frequent toxicities causing asparaginase truncations are hypersensitivity, pancreatitis and thrombosis. Especially hypersensitivity constitutes a problem due to silencing antibodies, not only in patients with clinical hypersensitivity but also in patients without clinical symptoms (silent inactivation).

In the NOPHO ALL2008 protocol asparaginase associated toxicities and truncation of asparaginase have been registered since the protocol opened in 2008. In addition asparaginase enzyme activity measurements have been done before every asparaginase administration and analyzed retrospectively.

The primary aim of this study was to investigate if patients with truncation of asparaginase or lack of asparaginase enzyme activity had a different risk of relapse compared to patients who received full asparaginase treatment. Secondary we aimed to explore if patients who received less than 50% of their planned asparaginase dosages had a different risk of relapse compared to those who received 50% or more.

Eligibility criteria: Inclusion Criteria:

- Children treated according to the NOPHO ALL2008 protocol from the 1st of July 2008 - 28th of February 2016.

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

Primary outcomes:
measure: Risk of relapse
timeFrame: 5 years
Secondary outcomes:
measure: 50% of asparagine doses
timeFrame: 5 years
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital, Department of Pediatrics Skejby Hospital
state: Aarhus N
Study officials:
References:
citation: Gottschalk Hojfeldt S, Grell K, Abrahamsson J, Lund B, Vettenranta K, Jonsson OG, Frandsen TL, Wolthers BO, Marquart HV, Vaitkeviciene G, Lepik K, Heyman M, Schmiegelow K, Albertsen BK. Relapse risk following truncation of pegylated asparaginase in childhood acute lymphoblastic leukemia. Blood. 2021 Apr 29;137(17):2373-2382. doi: 10.1182/blood.2020006583.