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

Acute Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01800643
• Other study ID #: Busulfan-2013
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: February 25, 2013
• Last updated: December 2, 2014
• Start date: March 2010
• Est. completion date: December 2014

Study information

• Verified date: December 2014
• Source: Hospital Israelita Albert Einstein
• Contact: Iracema Esteves, investigator
• Phone: (5511)963010921
• Email: iestevesmed[@]yahoo.com.br
• Is FDA regulated: No
• Health authority: Brazil: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Leukemia
• Chronic Leukemia
• Immunodeficiency
• Immunologic Deficiency Syndromes
• Leukemia
• Lymphoproliferative Disease
• Lymphoproliferative Disorders
• Myeloproliferative Disease
• Myeloproliferative Disorders

Intervention

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.

Locations

Country	Name	City	State
Brazil	Hospital Israelita Albert Einstein	Sao Paulo	SP

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Israelita Albert Einstein

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	2 years	Yes
Secondary	Overall Survival	Evaluation of 5-years overall survival in patients who underwent different formulations of busulfan during stem Cell Transplantation	5 years	Yes
Secondary	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	5 years	No
Secondary	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	1 year	No
Secondary	Toxicity	Evaluate hematological and non hematological toxicity in patients that underwent stem cell transplantation with busulfan in conditioning regimen	1 year	Yes