Busulfan Pharmacokinetic Analysis and GST Pharmacogenetic Profile in Adults Undergoing Hematological Stem Cell Transplantation

Completed

• Conditions: Acute Myeloid Leukemia

• Registration Number: NCT01608204
• Lead Sponsor: Rambam Health Care Campus

Brief Summary

The correlation between Busulfan Pharmacokinetics in AML transplanted patients and their GST (A1,T1,M1 and P1), MDR-1 genetic profile. If a pre-genetic testing of those genes can be utilized as biomarkers of SOS and/or HGVHD. This study is not an interventional study it is only checking the GST gene and MDR-1 gene

Detailed Description

BU levels are largely unpredictable, patients are often exposed to the toxic effects of inappropriate drug regimens before dose modifications can be made. Although the importance of TDM cannot be over emphasized, it entails trial and error and does not allow for pre- treatment dose optimization. This study, which provides an integration of genetic and pharmacokinetic data analysis of patients preconditioned for HSCT with high dose oral BU, aims to define biomarkers predictive of poor BU metabolism and clearance to prevent potential drug toxicity.This study is not an interventional study, only investigates the GST and MDR-1 genes in correlation with the "routine" Busulfan AUC done during the preparative regimen in HSCT for AML patients.

Study Timeline

• Study Start: 2010-01
• Primary Completion: 2011-12
• Study Completion: 2011-12
• Status Verified: 2012-05
• Study First Submitted: 2012-05-25
• Study First Submitted QC: 2012-05-29
• Study First Posted: 2012-05-30
• Last Update Submitted: 2013-06-10
• Last Update Posted: 2013-06-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 63

Inclusion Criteria

• Acute Myeloid Leukemia who are clinically selected for HSCT according to known protocols.

Exclusion Criteria

• Unable to give informed consent

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
If GST and ABCB1 genes modify busulfan pharmacokinetics in AML patients who will be transplanted	end of BMT transplantation	If individuals diagnosed with AML carrying the GSTP1 variant allele rs1695 (heterozygotes) are at risk of developing supra-therapeutic BU AUC due to lower BU clearance, and if combined polymorphisms in GSTM1 and ABCB1 (3435 or 2677) are associated with BU clearance rates and AUC.