Outcome Following Truncation of Asparaginase

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

Detailed Description
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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.

Official Title
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Outcome Following Truncation of Asparaginase in the NOPHO ALL2008 Protocol

Conditions
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Relapse Leukemia

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Exposed<br>Patients who had their asparaginase treatment truncated or had no asparaginase enzyme activity. | |
| Unexposed<br>Patients who did not have their asparaginase treatment truncated and had measurable asparaginase enzyme activity | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Risk of relapse | Do patients with truncation of asparaginase treatment or no enzyme activity (truncated) have a different risk of relapse compared to patients who have not been truncated and who have measurable enzyme activity (non-truncated) | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 50% of asparagine doses | Do patients who receive less than 50% of their planned asparaginase dosages have a different risk of relapse compared to those who receive 50% or more. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute lymphoblastic leukemia, Asparaginase, Truncation, Toxicitities