Pharmacokinetics and Immunogenicity of the First Doses of PEG-Asparaginase -An ALLTogether Pilot Study

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

Pharmacokinetics and Immunogenicity of the First Doses of PEG-Asparaginase -An ALLTogether Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04843150
• Other study ID #: A2G-pilot-asp
• Status: Completed
• Start date: July 1, 2020
• Est. completion date: October 1, 2023

Study information

• Verified date: February 2024
• Source: Aarhus University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Acute lymphoblastic leukemia (ALL) is the most common malignant disease in childhood. Survival rates exceed 90% in children and 75% in adults (aged 18-45 years). During the induction period Asparaginase is an indispensable part of the multiagent treatment, but is often associated with hypersensitivity, either with clinical allergy or silent inactivation. In both cases, Asparaginase is inactivated. It is well known that truncation of Asparaginase treatment due to inactivation reduces survival. To approach understanding Asparaginase dynamics and hypersensitivity in ALL patients it is important to examine the pharmacokinetics of Asparaginase. The aim of this study is to identify serological parameters for prediction of hypersensitivity reaction after the first doses of PEG-Asparaginase given intravenously on the ALLTogether protocol.

Description:

Asp enzyme activity is measurable in plasma, and trough levels above 100 IU/l secure effect. Patients, who have their treatment truncated, have inferior outcome. For many years prolonged Asp treatment for 30 weeks has been part of most protocols worldwide, but a recent Nordic randomized study showed that less asparaginase (8 doses vs 15 doses intramuscularly (IM)) results in the same disease-free survival and significant less toxicity in the less intensive treatment arm (6). Accordingly, in the current Western European protocol (ALLTogether) less Asp is now given. The Nordic Countries participate in this protocol. Unlike in the previous Nordic protocol, NOPHO ALL2008, in ALLTogether Asp will be initiated early during induction (day 4 compared to day 30) and given intravenously (IV) and not IM. In February 2017 it was approved by the NOPHO Board to do more extensive pharmacokinetic studies of IM administered PEG-asparaginase, as it has not been shown if IM or IV is preferably in respect to minimizing the incidence of hypersensitivity. Most study groups in the world use IV administration, thus NOPHO has a unique chance to illuminate inactivation after IM administration, also in adult patients. Other groups have not published this. For >50% of the patients in ALLTogether, the induction therapy has been reduced from 4 drugs to 3 drugs. This emphasizes the importance of optimal treatment from the beginning. Therapeutic Drug Monitoring (TDM) will identify patients without activity in order to change Asp preparation. Additional sampling close after the first dose of PEG-Asp is expected to identify these patients earlier, providing an opportunity to optimize their treatment for better disease-free survival. The aim of this study is to identify serological parameters for prediction of hypersensitivity reaction after the first dose of PEG-Asp given IV on the ALLTogether protocol.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 320
• Est. completion date: October 1, 2023
• Est. primary completion date: September 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Year to 45 Years

Eligibility

Inclusion Criteria:

• Treated for acute lymphoblastic leukemia (ALL) on the ALL2GETHER pilot protocol

Exclusion Criteria:

• none

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Locations

Country	Name	City	State
Denmark	Department of Pediatrics, Skejby Hospital	Aarhus
Denmark	Aarhus University Hospital, Denmark	Aarhus N

Sponsors (1)

Lead Sponsor	Collaborator
Aarhus University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with hypersensitivity Clinical allergy / silent inactivation	Patients with allergic reactions or silent inactivation	2018-2021