Acute Lymphoblastic LeukemiaNCT06195735
Forecasting Hypersensitivity Against PEG-asparaginase to Optimize Outcome in ALL
An observational study of Acute Lymphoblastic Leukemia, run by Aarhus University Hospital at 1 site in Denmark.
Trial summary
Asparaginase is a cornerstone in the treatment of acute lymphoblastic leukemia (ALL). Clinical hypersensitivity reactions and PEG-asparaginase inactivation is common (12-13% of the patients on the NOPHO (Nordic Society for Paediatric Haematology and Oncology) ALL2008 protocol) and has become even more frequent after… Read more about this study
- Who is it for?
- Ages Up to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Acute Lymphoblastic Leukemia
- How many people
- 649 participants
- Where
- 1 siteDenmark
- Study dates
- 17 Jul 2020to 21 Dec 2023
- How long will I take part?
- 323 Days
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 45 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: All patients with ALL 1-45 years of age treated on the ALLTOGETHER main protocol in the Nordic and Baltic countries.
Who may be able to join
- Treated for acute lymphoblastic leukemia (ALL) on the ALLTOGETHER main protocol
Who cannot join
- None
Trial locations and contacts
1 site in 1 country.
About this study
Asparaginase is a cornerstone in the treatment of acute lymphoblastic leukemia (ALL). Clinical hypersensitivity reactions and PEG-asparaginase inactivation is common (12-13% of the patients on the NOPHO (Nordic Society for Paediatric Haematology and Oncology) ALL2008 protocol) and has become even more frequent after changing to the current Western European ALL Treatment protocol ALLTogether, despite the PEG coat, leading to increased asparaginase clearance and treatment truncation. Suboptimal anticancer therapy occurs in an additional 3-4% of the patients, who encounter expedited asparaginase clearance but no allergy symptoms (silent inactivation).
The aim of this study is to validate and potentially refine an already existing PEG-asparaginase pharmacokinetic model on data from patients treated according to the A2G main protocol.
Read the detailed description
In comparison to the previous NOPHO ALL2008 protocol, the current A2G protocol aims at reducing the treatment intensity for patients with a good prognosis. More than 50% of the patients do no longer receive anthracyclines during induction therapy in order to avoid cardiotoxicity, and therefore the treatment relies more on PEG-asparaginase, which is given earlier than in previous NOPHO protocols. This underlines the additional importance of adequate asparaginase activity during the treatment period in order to have optimal treatment response on the predefined stratification days. Individual measurements (TDM) can help to identify patients with suboptimal activity and enable initiation of corrective measures, where current guidelines recommend an effective PEG-asparaginase trough concentration of ≥100 IU/L. In case of inactivation, patients are switched to the second line asparaginase formulation Erwinase, which is both expensive and very burdensome for the patients and hospitals because of need for frequent treatment. Patients that have their treatment truncated, have inferior outcome.
The present Western European ALL Treatment protocol ALLTogether (A2G) opened November 2018 as a pilot protocol in NOPHO, where 17% of the patients experienced hypersensitivity (14% clinical reactions and 3% silent inactivation). Early detection of allergic reactions and inactivity is important to avoid potential life threatening allergic reactions and a suboptimal treatment. Our study group has developed a PEG-asparaginase pharmacokinetic model to predict potential allergy and inactivation based on data from the A2G pilot protocol. Since then, the PEG-asparaginase treatment was changed due to inacceptable overall toxicity, which has now resulted in a doubling of hypersensitivity reactions. Hence, the pattern of enzyme clearance and immunogenicity may have changed.
Identification and prediction of increased clearance through asparaginase measurements during treatment will allow for early treatment adaptation, i.e., before suboptimal plasma levels have been reached. Timely identification of drug inactivation and treatment adaptation would therefore have potential to improve treatment outcome for a substantial number of the patients. The investigators aim to tackle this problem through pharmacokinetic-pharmacodynamic characterization of the relationships between dosage, asparaginase exposure and appearance of allergy symptoms in patients treated according to the A2G main protocol. This integrated knowledge can help facilitate development of tailored treatment strategies for individual patients.
- Conditions
- Acute Lymphoblastic Leukemia
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with hypersensitivity Clinical allergy / silent inactivation
Patients with allergic reactions or silent inactivation
Measured: 2020-2023
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2024
- Study start17 Jul 2020
- Primary completion21 Dec 2023
- Study completion21 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by Aarhus University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 649 participants (actual)
- Target duration
- 323 Days
Sponsor and investigators
- Lead sponsor
- Aarhus University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Uppsala University, University of Aarhus
- Responsible party
- Principal investigator, Birgitte Klug Albertsen, Aarhus University Hospital
- Investigators
- Birgitte K Albertsen, M.D., Principal investigator, Aarhus University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06195735
- Sponsor's protocol ID
- Asp_pharmacokinetic-model
- Status last verified
- Jan 2024
- First submitted
- 14 Dec 2023
- Last updated
- 8 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Forecasting Hypersensitivity Against PEG-asparaginase to Optimize Outcome in ALL
- ClinicalTrials.gov ID
- NCT06195735
- Acronym / sponsor ID
- Asp_pharmacokinetic-model
- Conditions
- Acute Lymphoblastic Leukemia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 649 participants (actual)
- Lead sponsor
- Aarhus University HospitalUniversity, hospital or other
- Collaborators
- Uppsala University, University of Aarhus
- Study start
- 17 Jul 2020 (actual)
- Primary completion
- 21 Dec 2023 (actual)
- Study completion
- 21 Dec 2023 (actual)
- First posted
- 8 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Asparaginase is a cornerstone in the treatment of acute lymphoblastic leukemia (ALL). Clinical hypersensitivity reactions and PEG-asparaginase inactivation is common (12-13% of the patients on the NOPHO (Nordic Society for Paediatric Haematology and Oncology) ALL2008 protocol) and has become even more frequent after changing to the current Western European ALL Treatment protocol ALLTogether, despite the PEG coat, leading to increased asparaginase clearance and treatment truncation. Suboptimal anticancer therapy occurs in an additional 3-4% of the patients, who encounter expedited asparaginase clearance but no allergy symptoms (silent inactivation).
The aim of this study is to validate and potentially refine an already existing PEG-asparaginase pharmacokinetic model on data from patients treated according to the A2G main protocol.
Detailed description
In comparison to the previous NOPHO ALL2008 protocol, the current A2G protocol aims at reducing the treatment intensity for patients with a good prognosis. More than 50% of the patients do no longer receive anthracyclines during induction therapy in order to avoid cardiotoxicity, and therefore the treatment relies more on PEG-asparaginase, which is given earlier than in previous NOPHO protocols. This underlines the additional importance of adequate asparaginase activity during the treatment period in order to have optimal treatment response on the predefined stratification days. Individual measurements (TDM) can help to identify patients with suboptimal activity and enable initiation of corrective measures, where current guidelines recommend an effective PEG-asparaginase trough concentration of ≥100 IU/L. In case of inactivation, patients are switched to the second line asparaginase formulation Erwinase, which is both expensive and very burdensome for the patients and hospitals because of need for frequent treatment. Patients that have their treatment truncated, have inferior outcome.
The present Western European ALL Treatment protocol ALLTogether (A2G) opened November 2018 as a pilot protocol in NOPHO, where 17% of the patients experienced hypersensitivity (14% clinical reactions and 3% silent inactivation). Early detection of allergic reactions and inactivity is important to avoid potential life threatening allergic reactions and a suboptimal treatment. Our study group has developed a PEG-asparaginase pharmacokinetic model to predict potential allergy and inactivation based on data from the A2G pilot protocol. Since then, the PEG-asparaginase treatment was changed due to inacceptable overall toxicity, which has now resulted in a doubling of hypersensitivity reactions. Hence, the pattern of enzyme clearance and immunogenicity may have changed.
Identification and prediction of increased clearance through asparaginase measurements during treatment will allow for early treatment adaptation, i.e., before suboptimal plasma levels have been reached. Timely identification of drug inactivation and treatment adaptation would therefore have potential to improve treatment outcome for a substantial number of the patients. The investigators aim to tackle this problem through pharmacokinetic-pharmacodynamic characterization of the relationships between dosage, asparaginase exposure and appearance of allergy symptoms in patients treated according to the A2G main protocol. This integrated knowledge can help facilitate development of tailored treatment strategies for individual patients.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Target follow-up
- 323 Days
Who may qualify
- Ages
- Up to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- All patients with ALL 1-45 years of age treated on the ALLTOGETHER main protocol in the Nordic and Baltic countries.
Key inclusion criteria (1 listed)
- Treated for acute lymphoblastic leukemia (ALL) on the ALLTOGETHER main protocol
Key exclusion criteria (1 listed)
- None
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Number of participants with hypersensitivity Clinical allergy / silent inactivation
Time frame: 2020-2023
Patients with allergic reactions or silent inactivation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Birgitte K Albertsen, M.D. principal investigator
Aarhus University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Lymphoblastic Leukemia, run by Aarhus University Hospital at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with hypersensitivity Clinical allergy / silent inactivation (time frame: 2020-2023). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2024.