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

Primary Purpose

Acute Leukemia, Chronic Leukemia, Lymphoproliferative Disease

Status
Unknown status
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
Analyze the pharmacokinetics of busulfan for transplantation
Sponsored by
Hospital Israelita Albert Einstein
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Leukemia focused on measuring Busulfan, plasmatic dosage, Stem Cell Transplantation

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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;

Sites / Locations

  • Hospital Israelita Albert EinsteinRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Orally Busulfan PK

Intravenously Busulfan PK

Arm Description

Evaluate the Pharmacokinetics of orally busulfan

Evaluate the Pharmacokinetics of intravenously busulfan

Outcomes

Primary Outcome Measures

Dosing of plasmatic levels of busulfan
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

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

Full Information

First Posted
February 25, 2013
Last Updated
December 2, 2014
Sponsor
Hospital Israelita Albert Einstein
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1. Study Identification

Unique Protocol Identification Number
NCT01800643
Brief Title
Evaluation of Plasmatic Levels of Busulfan in Patients Undergoing Hematopoietic Stem Cell Transplantation
Official Title
Evaluation of Plasmatic Levels of Busulfan in Patients Undergoing Hematopoietic Stem Cell Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
December 2014
Overall Recruitment Status
Unknown status
Study Start Date
March 2010 (undefined)
Primary Completion Date
December 2014 (Anticipated)
Study Completion Date
December 2014 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hospital Israelita Albert Einstein

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Leukemia, Chronic Leukemia, Lymphoproliferative Disease, Myeloproliferative Disease, Immunodeficiency
Keywords
Busulfan, plasmatic dosage, Stem Cell Transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Orally Busulfan PK
Arm Type
Other
Arm Description
Evaluate the Pharmacokinetics of orally busulfan
Arm Title
Intravenously Busulfan PK
Arm Type
Other
Arm Description
Evaluate the Pharmacokinetics of intravenously busulfan
Intervention Type
Other
Intervention Name(s)
Analyze the pharmacokinetics of busulfan for transplantation
Other Intervention Name(s)
Busulfan dosing, Busulfan Pharmacokinetics, Busilvex, Myleran
Intervention Description
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.
Primary Outcome Measure Information:
Title
Dosing of plasmatic levels of busulfan
Description
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
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Overall Survival
Description
Evaluation of 5-years overall survival in patients who underwent different formulations of busulfan during stem Cell Transplantation
Time Frame
5 years
Title
Cumulative incidence of relapse and non relapse mortality
Description
Evaluate 5-years cumulative incidence of relapse and non relapse mortality in patients that underwent stem cell transplantation with busulfan in conditioning regimen
Time Frame
5 years
Title
Disease Free Survival
Description
Evaluate 1-year Disease Free Survival in patients that underwent stem cell transplantation with busulfan in conditioning regimen who enter complete remission after
Time Frame
1 year
Title
Toxicity
Description
Evaluate hematological and non hematological toxicity in patients that underwent stem cell transplantation with busulfan in conditioning regimen
Time Frame
1 year

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility 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;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Iracema Esteves, investigator
Phone
(5511)963010921
Email
iestevesmed@yahoo.com.br
First Name & Middle Initial & Last Name or Official Title & Degree
Sandra Nakashima, nurse
Phone
(5511)21511128
Email
sandra.nakashima@einstein.br
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nelson Hamerschlak, Doctor
Organizational Affiliation
Hospital Israelita Albert Einstein
Official's Role
Study Chair
Facility Information:
Facility Name
Hospital Israelita Albert Einstein
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
05651901
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Iracema Esteves, Doctor
Phone
(5511)963010921
Email
iestevesmed@yahoo.com.br
First Name & Middle Initial & Last Name & Degree
Sandra Saemi Nakashima, Nurse
Phone
(5511)21511128
Email
sandra.nakashima@einstein.br
First Name & Middle Initial & Last Name & Degree
Fabio R Kerbauy, Doctor
First Name & Middle Initial & Last Name & Degree
Nelson Hamerschlak, Doctor
First Name & Middle Initial & Last Name & Degree
Iracema Esteves, Doctor

12. IPD Sharing Statement

Citations:
PubMed Identifier
31089278
Citation
Esteves I, Santos FPS, Fernandes JF, Seber A, Oliveira JSR, Hamerschlak N, Kerbauy FR, S Andersson B, de Lima M. Pharmacokinetics analysis results are similar for oral compared to intravenous busulfan in patients undergoing hematopoietic stem cell transplantation, except for the earlier onset of mucositis. A controlled clinical study. Bone Marrow Transplant. 2019 Nov;54(11):1799-1804. doi: 10.1038/s41409-019-0521-5. Epub 2019 May 14.
Results Reference
derived

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

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