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

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ClinicalTrials.gov Identifier: NCT01800643
Recruitment Status : Unknown
Verified December 2014 by Iracema Esteves, Hospital Israelita Albert Einstein.
Recruitment status was:  Recruiting
First Posted : February 28, 2013
Last Update Posted : December 3, 2014
Sponsor:
Information provided by (Responsible Party):
Iracema Esteves, Hospital Israelita Albert Einstein

Brief Summary:
The purpose of this prospective study is evaluate the best dose of busulfan for each patient undergoing Haematopoietic Stem Cell Transplantation

Condition or disease Intervention/treatment Phase
Acute Leukemia Chronic Leukemia Lymphoproliferative Disease Myeloproliferative Disease Immunodeficiency Other: Analyze the pharmacokinetics of busulfan for transplantation Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of Plasmatic Levels of Busulfan in Patients Undergoing Hematopoietic Stem Cell Transplantation
Study Start Date : March 2010
Estimated Primary Completion Date : December 2014
Estimated Study Completion Date : December 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Busulfan

Arm Intervention/treatment
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:
  • Busulfan dosing
  • Busulfan Pharmacokinetics
  • Busilvex
  • Myleran

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:
  • Busulfan dosing
  • Busulfan Pharmacokinetics
  • Busilvex
  • Myleran




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: 5 years ]
    Evaluation of 5-years overall survival in patients who underwent different formulations of busulfan during stem Cell Transplantation

  2. 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

  3. 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

  4. Toxicity [ Time Frame: 1 year ]
    Evaluate hematological and non hematological toxicity in patients that underwent stem cell transplantation with busulfan in conditioning regimen



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01800643


Contacts
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Contact: Iracema Esteves, investigator (5511)963010921 iestevesmed@yahoo.com.br
Contact: Sandra Nakashima, nurse (5511)21511128 sandra.nakashima@einstein.br

Locations
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Brazil
Hospital Israelita Albert Einstein Recruiting
Sao Paulo, SP, Brazil, 05651901
Contact: Iracema Esteves , Doctor    (5511)963010921    iestevesmed@yahoo.com.br   
Contact: Sandra Saemi Nakashima, Nurse    (5511)21511128    sandra.nakashima@einstein.br   
Sub-Investigator: Fabio R Kerbauy, Doctor         
Principal Investigator: Nelson Hamerschlak, Doctor         
Sub-Investigator: Iracema Esteves, Doctor         
Sponsors and Collaborators
Hospital Israelita Albert Einstein
Investigators
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Study Chair: Nelson Hamerschlak, Doctor Hospital Israelita Albert Einstein

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Responsible Party: Iracema Esteves, MD, Hospital Israelita Albert Einstein
ClinicalTrials.gov Identifier: NCT01800643     History of Changes
Other Study ID Numbers: Busulfan-2013
First Posted: February 28, 2013    Key Record Dates
Last Update Posted: December 3, 2014
Last Verified: December 2014

Keywords provided by Iracema Esteves, Hospital Israelita Albert Einstein:
Busulfan
plasmatic dosage
Stem Cell Transplantation

Additional relevant MeSH terms:
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Leukemia
Immunologic Deficiency Syndromes
Myeloproliferative Disorders
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Neoplasms
Immune System Diseases
Bone Marrow Diseases
Hematologic Diseases
Lymphatic Diseases
Immunoproliferative Disorders
Busulfan
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Myeloablative Agonists