Acute LeukemiaPhase 2/3NCT01800643
Evaluation of Plasmatic Levels of Busulfan in Patients Undergoing Hematopoietic Stem Cell Transplantation
A Phase 2/3 study testing Analyze the pharmacokinetics of busulfan for transplantation in people with Acute Leukemia and Chronic Leukemia, run by Hospital Israelita Albert Einstein at 1 site in Brazil.
Trial summary
The purpose of this prospective study is evaluate the best dose of busulfan for each patient undergoing Haematopoietic Stem Cell Transplantation Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Acute Leukemia, Chronic Leukemia, Lymphoproliferative Disease
- What is being tested?
- Analyze the pharmacokinetics of busulfan for transplantation
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteBrazil
- Study dates
- Mar 2010to Dec 2014
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Presence of infectious process in uncontrolled activity;
- Presence of psychiatric disorder;
- Pregnancy;
Trial locations and contacts
1 site in 1 country.
Brazil1 site, 1 recruiting
- Recruiting
Hospital Israelita Albert Einstein
São Paulo, São Paulo, 05651901
Iracema Esteves, Doctor, (5511)963010921, iestevesmed@yahoo.com.br
Sandra Saemi Nakashima, Nurse, (5511)21511128, sandra.nakashima@einstein.br
About this study
The purpose of this prospective study is evaluate the best dose of busulfan for each patient undergoing Haematopoietic Stem Cell Transplantation
Read the 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.
- Conditions
- Acute Leukemia, Chronic Leukemia, Lymphoproliferative Disease, Myeloproliferative Disease, Immunodeficiency
- Being tested
- Analyze the pharmacokinetics of busulfan for transplantation
- Keywords
- Busulfan, plasmatic dosage, Stem Cell Transplantation
- Medical subject headings
- Lymphoproliferative Disorders, Myeloproliferative Disorders, Immunologic Deficiency Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Analyze the pharmacokinetics of busulfan for transplantationOther
Also called Busulfan dosing, Busulfan Pharmacokinetics, Busilvex, Myleran
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.
| Study group | Role | What they receive |
|---|---|---|
| Orally Busulfan PK | Other | Evaluate the Pharmacokinetics of orally busulfan Receives: Other: Analyze the pharmacokinetics of busulfan for transplantation |
| Intravenously Busulfan PK | Other | Evaluate the Pharmacokinetics of intravenously busulfan Receives: Other: Analyze the pharmacokinetics of busulfan for transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 2 years
Secondary outcomes (4)
Overall Survival
Evaluation of 5-years overall survival in patients who underwent different formulations of busulfan during stem Cell Transplantation
Measured: 5 years
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
Measured: 5 years
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
Measured: 1 year
Toxicity
Evaluate hematological and non hematological toxicity in patients that underwent stem cell transplantation with busulfan in conditioning regimen
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2013 (estimated)
- Study startMar 2010
- Primary completionDec 2014 (estimated)
- Study completionDec 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital Israelita Albert Einstein
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Iracema Esteves, Hospital Israelita Albert Einstein
- Investigators
- Nelson Hamerschlak, Doctor, Study chair, Hospital Israelita Albert Einstein
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01800643
- Sponsor's protocol ID
- Busulfan-2013
- Status last verified
- Dec 2014
- First submitted
- 25 Feb 2013
- Last updated
- 3 Dec 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 31089278
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Plasmatic Levels of Busulfan in Patients Undergoing Hematopoietic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT01800643
- Acronym / sponsor ID
- Busulfan-2013
- Conditions
- Acute Leukemia, Chronic Leukemia, Lymphoproliferative Disease, Myeloproliferative Disease, Immunodeficiency
- Keywords
- Busulfan, plasmatic dosage, Stem Cell Transplantation
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Hospital Israelita Albert EinsteinUniversity, hospital or other
- Study start
- Mar 2010
- Primary completion
- Dec 2014 (estimated)
- Study completion
- Dec 2014 (estimated)
- First posted
- 28 Feb 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Orally Busulfan PK | Other | Other: Analyze the pharmacokinetics of busulfan for transplantationEvaluate the Pharmacokinetics of orally busulfan |
| Intravenously Busulfan PK | Other | Other: Analyze the pharmacokinetics of busulfan for transplantationEvaluate the Pharmacokinetics of intravenously busulfan |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- 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;
Key exclusion criteria (3 listed)
- Presence of infectious process in uncontrolled activity;
- Presence of psychiatric disorder;
- Pregnancy;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Analyze the pharmacokinetics of busulfan for transplantationAlso: Busulfan dosing, Busulfan Pharmacokinetics, Busilvex, MyleranEvaluate 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 | Intravenously Busulfan PK, Orally Busulfan PK |
Primary outcome
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
4 secondary outcomes
Overall Survival
Time frame: 5 years
Cumulative incidence of relapse and non relapse mortality
Time frame: 5 years
Disease Free Survival
Time frame: 1 year
Toxicity
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2014.
- Derived from this study: PubMed 31089278Esteves 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nelson Hamerschlak, Doctor study chair
Hospital Israelita Albert Einstein
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Analyze the pharmacokinetics of busulfan for transplantation in people with Acute Leukemia and Chronic Leukemia, run by Hospital Israelita Albert Einstein at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Iracema Esteves, investigator ((5511)963010921, iestevesmed@yahoo.com.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dosing of plasmatic levels of busulfan (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01800643, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2014.