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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
N_Krivoy, Rambam Health Care Campus
ClinicalTrials.gov Identifier:
NCT01608204
First received: May 25, 2012
Last updated: June 10, 2013
Last verified: May 2012
  Purpose

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
Acute Myeloid Leukemia

Study Type: Observational
Study Design: Time Perspective: Prospective

Resource links provided by NLM:


Further study details as provided by Rambam Health Care Campus:

Primary Outcome Measures:
  • If GST and ABCB1 genes modify busulfan pharmacokinetics in AML patients who will be transplanted [ Time Frame: end of BMT transplantation ] [ Designated as safety issue: No ]
    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


Enrollment: 63
Study Start Date: January 2010
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years to 67 Years
Genders Eligible for Study:   Both
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
  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.

No Contacts or Locations Provided
  More Information

No publications provided

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
Study First Received: May 25, 2012
Last Updated: June 10, 2013
Health Authority: Israel: Ministry of Health

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

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on July 22, 2014