Evaluation of Plasmatic Levels of Busulfan in Patients Undergoing Hematopoietic Stem Cell Transplantation

December 2, 2014 updated by: Iracema Esteves, Hospital Israelita Albert Einstein
The purpose of this prospective study is evaluate the best dose of busulfan for each patient undergoing Haematopoietic Stem Cell Transplantation

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

  • Busulfan is an alkylating antineoplastic agent used commonly during the conditioning regimen in patients undergoing Haematopoietic Stem Cell Transplantation (HSCT). Due to the fact that this drug has a variable metabolism in different individuals, the investigators performed the plasmatic dosage of chemotherapy before starting the conditioning regimen (test dose) as a way to predict the best dose to them during the conditioning. Busulfan toxicities depends on the "Area Under Curve" and Concentration Steady State (CSS).
  • The investigators randomized in groups according to the route of drug administration: per oral and intravenously. Dose test will be performed before conditioning and othe pharmacokinetics (Pk) study will be made in the first day of conditioning. The test dose of P.O busulfan will be 1 mg/Kg/dose and 32 mg/m2 for I.V busulfan. The target dose of busulfan during the conditioning will depends on the Pk obtained during the test dose. In the first day of regimen, other samples will be analysed and the new AUC will be adjusted. We will have a control group who have never performed monitoring before (retrospective group)
  • Test Dose for oral busulfan will be performed with peripheral blood samples at the time: 0h (before taking busulfan), 30', 1h, 1,5h, 2h, 3h, 4h, 5h and 6h. In the first day of conditioning other samples will be collected again in the same moments.
  • Test dose for I.V busulfan will be performed on time 0h, 30', 45', 1h, 2h, 3h, 4h, 5h, 6h and 8h after receiving I.V busulfan. If the patients will receive I.V busulfan during conditioning, the blood samples should be collected on time 0h, 30', 1h, 2h, 3h, 4h, 5h, 6h, 7h and 8h after taking busulfan. The blood samples will be centrifuged (4º C/ 3200 rpm/10 minutes) and analysed.
  • Patients will be monitored with pharmacokinetic's drug and clinical outcomes. The investigators will evaluate acute and chronic toxicities after Stem Cell Transplantation.

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • SP
      • Sao Paulo, SP, Brazil, 05651901
        • Recruiting
        • Hospital Israelita Albert Einstein
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Fabio R Kerbauy, Doctor
        • Principal Investigator:
          • Nelson Hamerschlak, Doctor
        • Sub-Investigator:
          • Iracema Esteves, Doctor

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of hematologic or non-hematologic pathology using as part of the conditioning regimen busulfan;
  • Men, women and children regardless of age;
  • Performance Status> 80 or ECOG <2;
  • Total bilirubin <2 mg / dl and transaminases <3 times the upper limit of normal;
  • Creatinine <1.5 mg / dl;
  • LVEF> 50% by echocardiogram or MUGA at rest;
  • Pulmonary function test with FEV1> 70%;
  • Consent form signed before the start of any specific procedure.

Exclusion Criteria:

  • Presence of infectious process in uncontrolled activity;
  • Presence of psychiatric disorder;
  • Pregnancy;

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Orally Busulfan PK
Evaluate the Pharmacokinetics of orally busulfan
Other: Analyze the pharmacokinetics of busulfan for transplantation
Evaluate the Bu pharmacokinetics (PK) when the drug will be received by P.O or I.V and we will establish the target "Area Under Curve- AUC" based on a single daily dose (test dose) before HSCT. The test dose of orally Bu is 1 mg/Kg and the blood samples are collected and processed in time: 0h, 30 min, 1h, 1,5h, 2h, 3h, 4h, 5h and 6h after drug intake. After extraction of the plasma samples busulfan, quantitative analyzes of busulfan on human plasma will be performed by the liquid chromatograph. For the patients that will receive intravenously busulfan, the test dose is 32 mg/m2 and blood samples are collected in time: 0h, 30', 45', 1h, 2h, 3h, 4h, 5h, 6h and 8h after drug intake. The dose during the conditioning will depend on the test dose and the AUC target.
Other Names:
  • Myleran
  • Busilvex
  • Busulfan dosing
  • Busulfan Pharmacokinetics
Other: Intravenously Busulfan PK
Evaluate the Pharmacokinetics of intravenously busulfan
Other: Analyze the pharmacokinetics of busulfan for transplantation
Evaluate the Bu pharmacokinetics (PK) when the drug will be received by P.O or I.V and we will establish the target "Area Under Curve- AUC" based on a single daily dose (test dose) before HSCT. The test dose of orally Bu is 1 mg/Kg and the blood samples are collected and processed in time: 0h, 30 min, 1h, 1,5h, 2h, 3h, 4h, 5h and 6h after drug intake. After extraction of the plasma samples busulfan, quantitative analyzes of busulfan on human plasma will be performed by the liquid chromatograph. For the patients that will receive intravenously busulfan, the test dose is 32 mg/m2 and blood samples are collected in time: 0h, 30', 45', 1h, 2h, 3h, 4h, 5h, 6h and 8h after drug intake. The dose during the conditioning will depend on the test dose and the AUC target.
Other Names:
  • Myleran
  • Busilvex
  • Busulfan dosing
  • Busulfan Pharmacokinetics

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dosing of plasmatic levels of busulfan
Time Frame: 2 years
To study the effectiveness dosing of busulfan plasma levels during the administration of orally busulfan or intravenous prior to HSCT (test dose) and correlate with the respective plasma measurements in the first days of conditioning
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: 5 years
Evaluation of 5-years overall survival in patients who underwent different formulations of busulfan during stem Cell Transplantation
5 years
Cumulative incidence of relapse and non relapse mortality
Time Frame: 5 years
Evaluate 5-years cumulative incidence of relapse and non relapse mortality in patients that underwent stem cell transplantation with busulfan in conditioning regimen
5 years
Disease Free Survival
Time Frame: 1 year
Evaluate 1-year Disease Free Survival in patients that underwent stem cell transplantation with busulfan in conditioning regimen who enter complete remission after
1 year
Toxicity
Time Frame: 1 year
Evaluate hematological and non hematological toxicity in patients that underwent stem cell transplantation with busulfan in conditioning regimen
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital Israelita Albert Einstein

Investigators

  • Study Chair: Nelson Hamerschlak, Doctor, Hospital Israelita Albert Einstein

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2010

Primary Completion (Anticipated)

December 1, 2014

Study Completion (Anticipated)

December 1, 2014

Study Registration Dates

First Submitted

February 25, 2013

First Submitted That Met QC Criteria

February 27, 2013

First Posted (Estimate)

February 28, 2013

Study Record Updates

Last Update Posted (Estimate)

December 3, 2014

Last Update Submitted That Met QC Criteria

December 2, 2014

Last Verified

December 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Busulfan-2013

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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