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

Hospital Israelita Albert Einstein

Status and phase: Unknown; Phase 3; Phase 2

Conditions: Immunodeficiency; Acute Leukemia; Chronic Leukemia; Myeloproliferative Disease; Lymphoproliferative Disease

Treatments: Other: Analyze the pharmacokinetics of busulfan for transplantation

Study type: Interventional

Funder types: Other

Identifiers

NCT01800643

Busulfan-2013

Details and patient eligibility

About

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

Full 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.

Enrollment: 100 estimated patients

Sex: All

Volunteers: No 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;

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 2 patient groups

Orally Busulfan PK

Other group

Description:

Evaluate the Pharmacokinetics of orally busulfan

Treatment:

Other: Analyze the pharmacokinetics of busulfan for transplantation

Intravenously Busulfan PK

Other group

Description:

Evaluate the Pharmacokinetics of intravenously busulfan

Treatment:

Other: Analyze the pharmacokinetics of busulfan for transplantation