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Polymorphisms and Busulfan Pharmacokinetic Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2017 by Swiss Pediatric Oncology Group
European Group for Blood and Marrow Transplantation
Information provided by (Responsible Party):
Swiss Pediatric Oncology Group Identifier:
First received: December 8, 2010
Last updated: January 31, 2017
Last verified: January 2017
Test the correlations between the pharmacogenetic and pharmacokinetic of Busulfan IV in children receiving hematopoietic stem cell transplantation.

Children Who Receive a Stem Cell Transplantation With Busulfan IV

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Other
Official Title: Polymorphisms and Busulfan Pharmacokinetic Study in Pediatric Transplnatation

Resource links provided by NLM:

Further study details as provided by Swiss Pediatric Oncology Group:

Primary Outcome Measures:
  • polymorphisms in genes involved in Busulfan pathways correlation with pharmacokinetic [ Time Frame: 1 year post hematopoietic stem cell transplantation ]

Secondary Outcome Measures:
  • polymorphisms in genes involved in Busulfan pathways correlation with toxicity [ Time Frame: 1 year post hematopoietic stem cell transplantation ]
  • polymorphisms in genes involved in Busulfan pathways correlation with survival [ Time Frame: 1 year post stem cell transplantation ]

Biospecimen Retention:   Samples With DNA
DNA from each patient are kept. Plasma from some centers are kept

Estimated Enrollment: 200
Study Start Date: February 2008
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Busulfan, pharmacogenetic, pharmacokinetic, children
Children who receive Busulfan IV and have a pharmacokinetic of Busulfan

Detailed Description:

Most of the drugs used to treat cancer are metabolized by hepatic enzymes such as cytochrome P450 or Glutathion-S-Transferase (GST). These enzymatic pathways can be more or less active in the drug's metabolism according to the given polymorphism of each patient (pharmacogenomics).

The current hypothesis is that some functional polymorphisms of genes, which control important enzymes in Busulfan metabolism, contribute to the observed interindividual variability in PK of this drug. This variability can hence predict the resistance as well as the toxicity from a drug in patients who have cancer. The pharmacokinetic profile of different drugs, which have a hepatic metabolism, can be dramatically modified by these polymorphisms. Busulfan is a major drug used in the conditioning regimen before hematopoietic stem cell transplantation, particularly in children in whom total body irradiation has to be avoided. This drug has a narrow therapeutic index. At a lower systemic exposure than the targeted one, Busulfan has insufficient activity and hence an increased risk of transplant rejection and leukemic relapse.

At higher systemic exposures, the toxicity risk increases dramatically with an elevated incidence of hepatic veno-occlusive disease (VOD). Pharmacokinetic monitoring of Busulfan allows optimal dosing. The recommended doses are based on the weight, body surface area or age. Nevertheless, a majority of patients will still need an adjustment of the dose administered after their first dose: this will result in a cumulative systemic exposure that will be over or under therapeutic. Busulfan is metabolized principally by the GSTA1, as well as by other GST enzymes like the GSTM1 and GSTP1. These enzymes are present in the liver as well as in the intestinal cells and are up regulated in the digestive system of young children.With this study we will look for the polymorphism in GST genes, look at the Busulfan IV pharmacokinetics and finally look at the GST alpha enzyme activity and see if there is a correlation with clinical end points. This study will also study any correlation with other genes (repair DNA genes, CYP etc..) that could be correlated with Busulfan and/or cyclophosphamide. This study will also allow to do some DNA banking for future studies in genetics. This multicentric study is sponsor by the Swiss pediatric Oncology Group and is a European Bone and Marrow Transplantation study open in 6 countries (Switzerland, Canada, Italy, Holland, Tscèque republic, ). Pilot study are first analyze with St. Justine Hospital then with the other center at a later stage.


Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
primary care clinic of pediatric

Inclusion Criteria:

  • Patients must be ≤ than 18 years of age at study entry on this protocol
  • The patient must receive iv Busulfan as part of his hematopoietic stem cell transplant conditioning regimen.
  • Each participating center has to go through a PK cross validation
  • All patients (or their legal guardians) must sign a document of informed consent that has been approved by the Institutional Human Review Committee.
  • Each center has to do his own PK of BU
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01257854

Contact: Ansari Marc, MD +41223824589
Contact: Duval Michel, MD

Canada, Quebec
Chu St Justine Recruiting
Montreal, Quebec, Canada, H3T1C5
Contact: Ansari Marc, MD         
Contact: Duval Michel, MD         
Principal Investigator: Ansari Marc, MD         
Alberta children's hospital Recruiting
Alberta, Canada
Contact: Lewis victor, MD         
Principal Investigator: lewis victor, MD         
Hopital Rebert de bré Recruiting
Paris, France
Contact: JH Dalle, PhD   
Principal Investigator: JH Dalle, MD, PhD         
Hopital Cantonal de Genève Recruiting
Geneva, Switzerland, 1206
Contact: Ansari Marc, MD    +41223824589   
Principal Investigator: Ansari Marc, MD         
Sub-Investigator: Krajinovic Maja         
Sponsors and Collaborators
Swiss Pediatric Oncology Group
European Group for Blood and Marrow Transplantation
Principal Investigator: Ansari Marc, MD Hopital CAntonal de Genève, Switzerland
  More Information


Responsible Party: Swiss Pediatric Oncology Group Identifier: NCT01257854     History of Changes
Other Study ID Numbers: 2009-018105-41
2009-018105-41 ( EudraCT Number )
Study First Received: December 8, 2010
Last Updated: January 31, 2017

Keywords provided by Swiss Pediatric Oncology Group:

Additional relevant MeSH terms:
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Myeloablative Agonists processed this record on April 26, 2017