Polymorphisms and Busulfan Pharmacokinetic Study

NCT01257854 | Unknown

• 1 other identifier: 2009-018105-41
• Study Type: observational
• Target: 200
• Locations: 3 countries
• Sites: 4

Brief Summary

Test the correlations between the pharmacogenetic and pharmacokinetic of Busulfan IV in children receiving hematopoietic stem cell transplantation.

Conditions

Children Who Receive a Stem Cell Transplantation With Busulfan IV

Keywords

busulfan; pharmacogenetic; pharmacokinetic; toxicity; survival

Outcome Measures

Primary Outcomes (1)

• polymorphisms in genes involved in Busulfan pathways correlation with pharmacokinetic

  1 year post hematopoietic stem cell transplantation

Secondary Outcomes (2)

• polymorphisms in genes involved in Busulfan pathways correlation with toxicity

  1 year post hematopoietic stem cell transplantation

• polymorphisms in genes involved in Busulfan pathways correlation with survival

  1 year post stem cell transplantation

Study Arms (1)

Busulfan, pharmacogenetic, pharmacokinetic, children

Children who receive Busulfan IV and have a pharmacokinetic of Busulfan

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

primary care clinic of pediatric

You may qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Geneva: lead
• European Society for Blood and Marrow Transplantation: collaborator

Study Sites (4)

Alberta children's hospital

Calgary, Alberta, Canada

ACTIVE NOT RECRUITING

Chu St Justine

Montreal, Quebec, H3T1C5, Canada

RECRUITING

Hopital Rebert Debré

Paris, France

ACTIVE NOT RECRUITING

Hopital Cantonal de Genève

Geneva, 1206, Switzerland

RECRUITING

Related Publications (13)

• Ansari M, Lauzon-Joset JF, Vachon MF, Duval M, Theoret Y, Champagne MA, Krajinovic M. Influence of GST gene polymorphisms on busulfan pharmacokinetics in children. Bone Marrow Transplant. 2010 Feb;45(2):261-7. doi: 10.1038/bmt.2009.143. Epub 2009 Jul 6.

  PMID: 19584821 BACKGROUND

• Ansari M, Krajinovic M. Can the pharmacogenetics of GST gene polymorphisms predict the dose of busulfan in pediatric hematopoietic stem cell transplantation? Pharmacogenomics. 2009 Nov;10(11):1729-32. doi: 10.2217/pgs.09.135. No abstract available.

  PMID: 19891548 BACKGROUND

• Ansari M, Rezgui MA, Theoret Y, Uppugunduri CR, Mezziani S, Vachon MF, Desjean C, Rousseau J, Labuda M, Przybyla C, Duval M, Champagne M, Peters C, Bittencourt H, Krajinovic M; Pediatric Disease Working Parties of the European Blood and Marrow Transplant Group. Glutathione S-transferase gene variations influence BU pharmacokinetics and outcome of hematopoietic SCT in pediatric patients. Bone Marrow Transplant. 2013 Jul;48(7):939-46. doi: 10.1038/bmt.2012.265. Epub 2013 Jan 7.

  PMID: 23292236 RESULT

• Ansari M, Theoret Y, Rezgui MA, Peters C, Mezziani S, Desjean C, Vachon MF, Champagne MA, Duval M, Krajinovic M, Bittencourt H; Pediatric Disease Working Parties of the European Blood and Marrow Transplant Group. Association between busulfan exposure and outcome in children receiving intravenous busulfan before hematopoietic stem cell transplantation. Ther Drug Monit. 2014 Feb;36(1):93-9. doi: 10.1097/FTD.0b013e3182a04fc7.

  PMID: 24061446 RESULT

• Huezo-Diaz P, Uppugunduri CR, Tyagi AK, Krajinovic M, Ansari M. Pharmacogenetic aspects of drug metabolizing enzymes in busulfan based conditioning prior to allogenic hematopoietic stem cell transplantation in children. Curr Drug Metab. 2014 Mar;15(3):251-64. doi: 10.2174/1389200215666140202214012.

  PMID: 24524663 RESULT

• Uppugunduri CR, Rezgui MA, Diaz PH, Tyagi AK, Rousseau J, Daali Y, Duval M, Bittencourt H, Krajinovic M, Ansari M. The association of cytochrome P450 genetic polymorphisms with sulfolane formation and the efficacy of a busulfan-based conditioning regimen in pediatric patients undergoing hematopoietic stem cell transplantation. Pharmacogenomics J. 2014 Jun;14(3):263-71. doi: 10.1038/tpj.2013.38. Epub 2013 Oct 29.

  PMID: 24165757 RESULT

• Acosta-Martin AE, Antinori P, Uppugunduri CRS, Daali Y, Ansari M, Scherl A, Muller M, Lescuyer P. Detection of busulfan adducts on proteins. Rapid Commun Mass Spectrom. 2016 Dec 15;30(23):2517-2528. doi: 10.1002/rcm.7730.

  PMID: 27599297 RESULT

• Bartelink IH, Lalmohamed A, van Reij EM, Dvorak CC, Savic RM, Zwaveling J, Bredius RG, Egberts AC, Bierings M, Kletzel M, Shaw PJ, Nath CE, Hempel G, Ansari M, Krajinovic M, Theoret Y, Duval M, Keizer RJ, Bittencourt H, Hassan M, Gungor T, Wynn RF, Veys P, Cuvelier GD, Marktel S, Chiesa R, Cowan MJ, Slatter MA, Stricherz MK, Jennissen C, Long-Boyle JR, Boelens JJ. Association of busulfan exposure with survival and toxicity after haemopoietic cell transplantation in children and young adults: a multicentre, retrospective cohort analysis. Lancet Haematol. 2016 Nov;3(11):e526-e536. doi: 10.1016/S2352-3026(16)30114-4. Epub 2016 Oct 13.

  PMID: 27746112 RESULT

• Huezo-Diaz Curtis P, Uppugunduri CRS, Muthukumaran J, Rezgui MA, Peters C, Bader P, Duval M, Bittencourt H, Krajinovic M, Ansari M. Association of CTH variant with sinusoidal obstruction syndrome in children receiving intravenous busulfan and cyclophosphamide before hematopoietic stem cell transplantation. Pharmacogenomics J. 2018 Jan;18(1):64-69. doi: 10.1038/tpj.2016.65. Epub 2016 Oct 25.

  PMID: 27779248 RESULT

• Ansari M, Curtis PH, Uppugunduri CRS, Rezgui MA, Nava T, Mlakar V, Lesne L, Theoret Y, Chalandon Y, Dupuis LL, Schechter T, Bartelink IH, Boelens JJ, Bredius R, Dalle JH, Azarnoush S, Sedlacek P, Lewis V, Champagne M, Peters C, Bittencourt H, Krajinovic M. GSTA1 diplotypes affect busulfan clearance and toxicity in children undergoing allogeneic hematopoietic stem cell transplantation: a multicenter study. Oncotarget. 2017 Aug 27;8(53):90852-90867. doi: 10.18632/oncotarget.20310. eCollection 2017 Oct 31.

  PMID: 29207608 RESULT

• Waespe N, Mlakar SJ, Dupanloup I, Rezgui MA, Bittencourt H, Krajinovic M, Kuehni CE, Nava T, Ansari M. A novel integrative multi-omics approach to unravel the genetic determinants of rare diseases with application in sinusoidal obstruction syndrome. PLoS One. 2023 Apr 5;18(4):e0281892. doi: 10.1371/journal.pone.0281892. eCollection 2023.

  PMID: 37018234 DERIVED

• Jurkovic Mlakar S, Uppugunduri SCR, Nava T, Mlakar V, Golay H, Robin S, Waespe N, Rezgui MA, Chalandon Y, Boelens JJ, Bredius RGM, Dalle JH, Peters C, Corbacioglu S, Bittencourt H, Krajinovic M, Ansari M; paediatric diseases working party of the European society for blood and marrow transplantation. GSTM1 and GSTT1 double null genotypes determining cell fate and proliferation as potential risk factors of relapse in children with hematological malignancies after hematopoietic stem cell transplantation. J Cancer Res Clin Oncol. 2022 Jan;148(1):71-86. doi: 10.1007/s00432-021-03769-2. Epub 2021 Sep 9.

  PMID: 34499222 DERIVED

• Uppugunduri CRS, Storelli F, Mlakar V, Huezo-Diaz Curtis P, Rezgui A, Theoret Y, Marino D, Doffey-Lazeyras F, Chalandon Y, Bader P, Daali Y, Bittencourt H, Krajinovic M, Ansari M. The Association of Combined GSTM1 and CYP2C9 Genotype Status with the Occurrence of Hemorrhagic Cystitis in Pediatric Patients Receiving Myeloablative Conditioning Regimen Prior to Allogeneic Hematopoietic Stem Cell Transplantation. Front Pharmacol. 2017 Jul 11;8:451. doi: 10.3389/fphar.2017.00451. eCollection 2017.

  PMID: 28744217 DERIVED

Related Links

• European Society for Blood and Marrow Transplantation (EBMT) - Pediatric Diseases Working Party

Biospecimen

Retention: SAMPLES WITH DNA

DNA from each patient are kept. Plasma from some centers are kept

Study Officials

• Marc Ansari, MD, PhD

  Hopital Cantonal de Genève, Switzerland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marc Ansari, MD, PhD

CONTACT

+41223824589; marc.ansari@hcuge.ch

Michel Duval, MD

CONTACT

michel.duval@umontreal.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: December 8, 2010
• First Posted: December 10, 2010
• Study Start: February 1, 2008
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: April 28, 2021

Record last verified: 2021-04

Locations

CH (1); FR (1); CA (2)