LeukemiaNCT01025804
Pharmacokinetics of Asparaginase and Antibody Formation in Interfant-06
An observational study of Leukemia, run by Aarhus University Hospital at 6 sites in 5 countries.
Trial summary
Asparaginase is an important drug in the treatment of childhood leukemia including in infant (<1 year). The prognosis for infants is bad. Information about drug metabolism in neonates and infants is scarce as well as the reactions of an immature immune system to foreign proteins. Read more about this study
- Who is it for?
- Ages 1 hour to 1 year
- Conditions the study is for
- Leukemia
- How many people
- 15 participants
- Where
- 6 sitesin 5 countries
- Study dates
- Dec 2009to Dec 2015
- 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 1 hour to 1 year
- All sexes
- No healthy volunteers
- Child
Study population: Infants (children < 1 year) with ALL treated according to Interfant-06 at one of the Pediatric Oncology Centers in the Nordic Countries
Who may be able to join
- infants <1 year at diagnosis
- diagnosed with ALL
- treated according to the international Interfant-06 protocol
- treated at one of the pediatric oncological centers in the Nordic countries
Who cannot join
- children >1 year at diagnosis
Trial locations and contacts
6 sites in 5 countries.
6 sites in 5 countries
Denmark2 sites
Aarhus University Hospital, Department of Pediatrics Skejby Hospital
Aarhus, Aarhus N, 8200
Rigshospitalet
Copenhagen, 2100
About this study
Official title: Post-marketing Surveillance Study of the Pharmacokinetics of Asparaginase and Antibody Formation in Interfant-06
Asparaginase is an important drug in the treatment of childhood leukemia including in infant (<1 year). The prognosis for infants is bad.
Information about drug metabolism in neonates and infants is scarce as well as the reactions of an immature immune system to foreign proteins. The aims of this study is to describe the metabolism (pharmacokinetics) of asparaginase after administration intramuscularly and to evaluate the formation of antibodies against the drug (enzyme) during treatment in order to optimize the asparaginase treatment in infants in the future.
Read the detailed description
Combination chemotherapy for acute lymphoblastic leukaemia (ALL) usually includes a bacterial L-asparaginase enzyme derived from Escherichia coli or Erwinia species. Several studies have described the pharmacokinetics in children above 1 year of age of asparaginase given intramuscularly as well as intravenously. The development of anti-asparaginase antibodies to these foreign proteins has also been described.
Chemotherapy for infant ALL also includes L-asparaginase. However, the pharmacokinetics of asparaginase and antibody formation in infants is needed to be described to optimize therapy for this group of patients who have a doubtful prognosis.
Background In general the information about drug metabolism in neonates and infants is scarce as well as the reactions of an immature immune system to foreign proteins. Several pharmacokinetic studies have been performed in children above one year of age, but no data is available about pharmacokinetics and antibody formation during treatment with any asparaginase preparation in infants.
Pharmacokinetics:
Asparaginase is used in the treatment of childhood ALL since it depletes the blood of asparagines, which can be synthesized by normal cells but not by leukemic lymphoblasts. It has been shown that serum activities above 100 IU/l ensure depletion of asparagine in serum and CNS. In many cases even values considerably lower than 100 IU/l will deplete asparagine from the serum1-5.
In the Interfant-06 protocol the doses of asparaginase are adopted from childhood ALL-protocols without scientific foundation. Infants may metabolise asparaginase differently and thus may not achieve amino acid depletion.
Antibody formation:
Asparaginase is a foreign protein for the human body, so patients may develop antibodies against it, resulting in allergic reactions (probably mediated by IgE-antibodies) or silent antibodies (IgG antibodies, blocking the effect of the enzyme). In the first case treatment most often is stopped and in the second case treatment is insufficient6-7, and thus giving the patient a poorer prognosis in both cases.
In Interfant-06 patients are treated with native E.coli asparaginase for a period followed by PEG-asparaginase later during their treatment. Studies in older children have shown that approximately 1/3 of the patients develop IgG-antibodies against native E.coli after 5-6 doses7. Other studies have shown that IgG-antibodies against native E.coli asparaginase cross-react with PEG-asparaginase, resulting in a faster clearance of the enzyme8. Allergic reactions (any grade) to native E.coli asparaginase are encountered in approximately 30 % of children11-12. There is no knowledge about the frequency of antibody formation during asparaginase therapy in infants.
Aim
The study has the purposes:
- to describe the pharmacokinetics of intramuscular native E.coli and PEG-asparaginase in children below 1 year at diagnosis
- to evaluate antibody formation during asparaginase treatment with E.coli followed by PEG-asparaginase in infants
- Conditions
- Leukemia
- Keywords
- Interfant-06, Infant ALL, Asparaginase, Pharmacokinetics of asparaginase, Antibody formation
- Medical subject headings
- Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Infants | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
pharmacokinetics, antibody formation, side effects
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2009 (estimated)
- Study startDec 2009
- Primary completionDec 2014
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for 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
- Case only
- Time perspective
- Prospective
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aarhus University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Birgitte Klug Albertsen, Aarhus University Hospital
- Investigators
- Birgitte K Albertsen, MD, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01025804
- Sponsor's protocol ID
- Interfant-06, NOPHO
- Other IDs
- register identifier
- Status last verified
- Mar 2016
- First submitted
- 2 Dec 2009
- Last updated
- 4 Mar 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Albertsen BK, Harila-Saari A, Jahnukainen K, Lahteenmaki P, Riikonen P, Mottonen M, Lausen B. Asparaginase treatment in infants with acute lymphoblastic leukemia; pharmacokinetics and asparaginase hypersensitivity in Interfant-06. Leuk Lymphoma. 2019 Jun;60(6):1469-1475. doi: 10.1080/10428194.2018.1538507. Epub 2019 Jan 11.
PubMed 30632847
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Post-marketing Surveillance Study of the Pharmacokinetics of Asparaginase and Antibody Formation in Interfant-06
- ClinicalTrials.gov ID
- NCT01025804
- Acronym / sponsor ID
- Interfant-06, NOPHO
- Conditions
- Leukemia
- Keywords
- Interfant-06, Infant ALL, Asparaginase, Pharmacokinetics of asparaginase, Antibody formation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Aarhus University HospitalUniversity, hospital or other
- Study start
- Dec 2009
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 4 Dec 2009 (estimated)
- 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 an important drug in the treatment of childhood leukemia including in infant (<1 year). The prognosis for infants is bad.
Information about drug metabolism in neonates and infants is scarce as well as the reactions of an immature immune system to foreign proteins. The aims of this study is to describe the metabolism (pharmacokinetics) of asparaginase after administration intramuscularly and to evaluate the formation of antibodies against the drug (enzyme) during treatment in order to optimize the asparaginase treatment in infants in the future.
Detailed description
Combination chemotherapy for acute lymphoblastic leukaemia (ALL) usually includes a bacterial L-asparaginase enzyme derived from Escherichia coli or Erwinia species. Several studies have described the pharmacokinetics in children above 1 year of age of asparaginase given intramuscularly as well as intravenously. The development of anti-asparaginase antibodies to these foreign proteins has also been described.
Chemotherapy for infant ALL also includes L-asparaginase. However, the pharmacokinetics of asparaginase and antibody formation in infants is needed to be described to optimize therapy for this group of patients who have a doubtful prognosis.
Background In general the information about drug metabolism in neonates and infants is scarce as well as the reactions of an immature immune system to foreign proteins. Several pharmacokinetic studies have been performed in children above one year of age, but no data is available about pharmacokinetics and antibody formation during treatment with any asparaginase preparation in infants.
Pharmacokinetics:
Asparaginase is used in the treatment of childhood ALL since it depletes the blood of asparagines, which can be synthesized by normal cells but not by leukemic lymphoblasts. It has been shown that serum activities above 100 IU/l ensure depletion of asparagine in serum and CNS. In many cases even values considerably lower than 100 IU/l will deplete asparagine from the serum1-5.
In the Interfant-06 protocol the doses of asparaginase are adopted from childhood ALL-protocols without scientific foundation. Infants may metabolise asparaginase differently and thus may not achieve amino acid depletion.
Antibody formation:
Asparaginase is a foreign protein for the human body, so patients may develop antibodies against it, resulting in allergic reactions (probably mediated by IgE-antibodies) or silent antibodies (IgG antibodies, blocking the effect of the enzyme). In the first case treatment most often is stopped and in the second case treatment is insufficient6-7, and thus giving the patient a poorer prognosis in both cases.
In Interfant-06 patients are treated with native E.coli asparaginase for a period followed by PEG-asparaginase later during their treatment. Studies in older children have shown that approximately 1/3 of the patients develop IgG-antibodies against native E.coli after 5-6 doses7. Other studies have shown that IgG-antibodies against native E.coli asparaginase cross-react with PEG-asparaginase, resulting in a faster clearance of the enzyme8. Allergic reactions (any grade) to native E.coli asparaginase are encountered in approximately 30 % of children11-12. There is no knowledge about the frequency of antibody formation during asparaginase therapy in infants.
Aim
The study has the purposes:
- to describe the pharmacokinetics of intramuscular native E.coli and PEG-asparaginase in children below 1 year at diagnosis
- to evaluate antibody formation during asparaginase treatment with E.coli followed by PEG-asparaginase in infants
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Infants | – | – |
Who may qualify
- Ages
- 1 hour to 1 year
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- Infants (children < 1 year) with ALL treated according to Interfant-06 at one of the Pediatric Oncology Centers in the Nordic Countries
Key inclusion criteria (4 listed)
- infants <1 year at diagnosis
- diagnosed with ALL
- treated according to the international Interfant-06 protocol
- treated at one of the pediatric oncological centers in the Nordic countries
Key exclusion criteria (1 listed)
- children >1 year at diagnosis
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
pharmacokinetics, antibody formation, side effects
Time frame: 1 year
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 4 Mar 2016.
- Derived from this study: PubMed 30632847Albertsen BK, Harila-Saari A, Jahnukainen K, Lahteenmaki P, Riikonen P, Mottonen M, Lausen B. Asparaginase treatment in infants with acute lymphoblastic leukemia; pharmacokinetics and asparaginase hypersensitivity in Interfant-06. Leuk Lymphoma. 2019 Jun;60(6):1469-1475. doi: 10.1080/10428194.2018.1538507. Epub 2019 Jan 11.
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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, MD study chair
6 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Leukemia, run by Aarhus University Hospital at 6 sites in 5 countries.
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 4 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 4 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Denmark, Finland, Iceland, Norway, Sweden. 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?
pharmacokinetics, antibody formation, side effects (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01025804, which also lists 1 linked publication.
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 4 Mar 2016; AzTrials last refreshed its copy on 8 Nov 2026.