Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Pharmacokinetics of Asparaginase and Antibody Formation in Interfant-06

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01025804
Recruitment Status : Completed
First Posted : December 4, 2009
Last Update Posted : March 4, 2016
Sponsor:
Information provided by (Responsible Party):
Birgitte Klug Albertsen, Aarhus University Hospital

Study Description
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief 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. 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.


Condition or disease
Leukemia

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
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Observational
Actual Enrollment : 15 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Post-marketing Surveillance Study of the Pharmacokinetics of Asparaginase and Antibody Formation in Interfant-06
Study Start Date : December 2009
Actual Primary Completion Date : December 2014
Actual Study Completion Date : December 2015

Resource links provided by the National Library of Medicine


Groups and Cohorts
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Group/Cohort
Infants


Outcome Measures
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. pharmacokinetics, antibody formation, side effects [ Time Frame: 1 year ]

Biospecimen Retention:   Samples Without DNA
Serum is retained for measurement of enzyme activities and antibodies

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 1 Year   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Infants (children < 1 year) with ALL treated according to Interfant-06 at one of the Pediatric Oncology Centers in the Nordic Countries
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • children >1 year at diagnosis
Contacts and Locations
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01025804


Locations
Layout table for location information
Denmark
Aarhus University Hospital, Department of Pediatrics Skejby Hospital
Aarhus, Aarhus N, Denmark, 8200
Rigshospitalet
Copenhagen, Denmark, 2100
Finland
Helsinki University Hospital
Helsinki, Finland
Iceland
University Hospital Reykjavik
Reykjavik, Iceland
Norway
Rikshospitalet
Oslo, Norway
Sweden
Karolinska
Stockholm, Sweden
Sponsors and Collaborators
Aarhus University Hospital
Investigators
Layout table for investigator information
Study Chair: Birgitte K Albertsen, MD
More Information
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Birgitte Klug Albertsen, MD, PhD, Aarhus University Hospital
ClinicalTrials.gov Identifier: NCT01025804    
Other Study ID Numbers: Interfant-06, NOPHO
register identifier ( Registry Identifier: NOPHO )
First Posted: December 4, 2009    Key Record Dates
Last Update Posted: March 4, 2016
Last Verified: March 2016
Keywords provided by Birgitte Klug Albertsen, Aarhus University Hospital:
Interfant-06
Infant ALL
Asparaginase
Pharmacokinetics of asparaginase
Antibody formation