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

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ClinicalTrials.gov Identifier: NCT01608204
Recruitment Status : Completed
First Posted : May 30, 2012
Last Update Posted : June 11, 2013
Sponsor:
Information provided by (Responsible Party):
N_Krivoy, 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

Condition or disease
Acute Myeloid Leukemia

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 Type : Observational
Actual Enrollment : 63 participants
Time Perspective: Prospective
Study Start Date : January 2010
Actual Primary Completion Date : December 2011
Actual Study Completion Date : December 2011





Primary Outcome Measures :
  1. If GST and ABCB1 genes modify busulfan pharmacokinetics in AML patients who will be transplanted [ Time Frame: 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.


Biospecimen Retention:   Samples With DNA
Peripheral Blood was used for DNA extraction


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Ages Eligible for Study:   18 Years to 67 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Adults suffering from AML who were selected to be treated by Hematological Stem Cell Transplantation
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • Unable to give informed consent

Responsible Party: N_Krivoy, Director Clinical Pharmacology Unit, Rambam Health Care Campus
ClinicalTrials.gov Identifier: NCT01608204     History of Changes
Other Study ID Numbers: BU/MEAdultPK/PGx1
First Posted: May 30, 2012    Key Record Dates
Last Update Posted: June 11, 2013
Last Verified: May 2012

Keywords provided by N_Krivoy, Rambam Health Care Campus:
Pharmacokinetics
Busulfan
Polymorphism
GST
MDR-1(p-Glycoprotein)
Acute Myeloid Leukemia adult patients

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia
Neoplasms by Histologic Type
Neoplasms
Busulfan
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Myeloablative Agonists