- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04843150
Pharmacokinetics and Immunogenicity of the First Doses of PEG-Asparaginase -An ALLTogether Pilot Study
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.
Study Overview
Status
Conditions
Detailed 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.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Contact
- Name: Birgitte K Albertsen, MD
- Phone Number: 6732 9495566
- Email: biralber@rm.dk
Study Locations
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Aarhus, Denmark, 8200
- Department of Pediatrics, Skejby Hospital
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Aarhus N, Denmark, 8200
- Aarhus University Hospital, Denmark
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Treated for acute lymphoblastic leukemia (ALL) on the ALL2GETHER pilot protocol
Exclusion Criteria:
- none
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Other
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of participants with hypersensitivity Clinical allergy / silent inactivation
Time Frame: 2018-2021
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Patients with allergic reactions or silent inactivation
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2018-2021
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Birgitte K Albertsen, MD, M.D., PhD, Associate Professor, Aarhus University Hospital
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- A2G-pilot-asp
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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