Clinical trial NCT01800643: 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
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Acute Leukemia
Chronic Leukemia
Lymphoproliferative Disease
Myeloproliferative Disease
Immunodeficiency
Keywords: Busulfan
plasmatic dosage
Stem Cell Transplantation
Lead sponsor: Hospital Israelita Albert Einstein
Sponsor class: OTHER
First posted: 2013-02-28
Enrollment: 100
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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;

Primary outcomes:
measure: Dosing of plasmatic levels of busulfan
timeFrame: 2 years
Secondary outcomes:
measure: Overall Survival
timeFrame: 5 years
measure: Cumulative incidence of relapse and non relapse mortality
timeFrame: 5 years
measure: Disease Free Survival
timeFrame: 1 year
measure: Toxicity
timeFrame: 1 year
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: Hospital Israelita Albert Einstein
state: SP
Study officials:
affiliation: Hospital Israelita Albert Einstein
name: Nelson Hamerschlak, Doctor
role: STUDY_CHAIR
References:
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.