Hematological MalignancyPhase 4NCT02372357
A New Dosing Regimen for Posaconazole Prophylaxis in Children Based on Body Surface Area
A Phase 4 study testing Posaconazole prophylaxis 120 mg/m² tid and Blood sampling in people with Hematological Malignancy, run by Universitaire Ziekenhuizen KU Leuven at 2 sites in 2 countries.
Trial summary
A new prophylactic posaconazole dosing regimen of 120mg/m² tid is evaluated pharmacologically in children 13 years and younger, suffering from a hematologic malignancy. Read more about this study
- Who is it for?
- Ages 2 to 13 years
- Conditions the study is for
- Hematological Malignancy
- What is being tested?
- Posaconazole prophylaxis 120 mg/m² tid and Blood sampling
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Feb 2012to Oct 2014
- Phase
- Phase 4
- 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 2 to 13 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 2-13 years of age
- hematological malignancy
- need for antifungal prophylaxis because of neutropenia caused by chemotherapy and/or hematopoietic stem cell transplantation.
Who cannot join
- <2 years of age
- > 13 years of age
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Belgium1 site
Catholic University Leuven - Department of Pharmaceutical and Pharmacological Sciences
Leuven, Vlaams-Brabant, 3000
About this study
Official title: A New Dosing Regimen for Posaconazole Prophylaxis in Children Based in Body Surface Area
A new prophylactic posaconazole dosing regimen of 120mg/m² tid is evaluated pharmacologically in children 13 years and younger, suffering from a hematologic malignancy.
Read the detailed description
Invasive fungal infections (IFI), especially candidiasis and aspergillosis, are a serious threat to immunocompromised pediatric patients. Because diagnosis of IFI in pediatric patients is difficult, due to the lack of specific clinical and radiological signs and the low sensitivity of blood cultures, antifungal prophylaxis would largely optimize management of IFI in this setting. However, antifungal prophylaxis remains a matter of debate, as no clear consensus has yet been reached about the optimal drug. Very limited pediatric data are available, and current guidelines are mainly based on extrapolation of adult data. Fluconazole remains the drug of choice in many centers, despite its non-mould active spectrum. Itraconazole, liposomal amphotericin B and nebulized lipid-formulations of amphotericin B are often used off-label, although neither their pharmacokinetics (PK), nor their efficacy and safety have been documented in a proper way. Voriconazole is registered for children older than 2 years of age, mainly in the treatment setting. Moreover, its extremely variable PK profile, uncertainty about adequate exposure and risk for hepatotoxicity and neurotoxicity do not favor the use of voriconazole in this setting. Finally, micafungin only has low recommendation in the prophylactic setting, due to the possible risk of liver tumours.
Posaconazole would be the ideal antifungal drug to be used prophylactically in children for many reasons. It has a broad spectrum of activity, including emerging moulds like Aspergillus spp. and Zygomycetes. It has shown to be superior over fluconazole and itraconazole in preventing IFI in adults and it has a favorable safety profile, with nausea and vomiting being the most frequently encountered adverse events. However, lack of pharmacokinetic (PK) data in children younger than 13 years of age, results in only a marginal recommendation in current guidelines [8]. Little information is available about the correct dosing regimen of the available oral suspension in young pediatric patients, and similar to what is observed in adults, often very low posaconazole plasma concentrations (PPCs) are being measured. Therefore, therapeutic drug monitoring (TDM) is recommended to reach adequate PPCs above 0.5mg/L or 0.7 mg/L followed by increasing the dose as needed.
In this study, the pharmacokinetics of a newly introduced dosing regimen for posaconazole oral suspension is investigated, based on body surface area (BSA), used prophylactically in immunocompromised children under the age of 13.
Pediatric patients, admitted to the hospital to receive chemotherapy or hematopoietic stem cell transplantation are treated prophylactically with posaconazole 120mg/m² tid.
At steady state (after at least 7 days of posaconazole treatment), 9 plasma samples are collected in these patients to calculate the area under the curve and other relevant PK parameters as maximum and minimal plasma concentrations, volume of distribution, halflife and clearance rate.
Finally, these results will be compared to adult data in literature to evaluate whether 120mg/m² tid an adequate dosing regimen in children.
- Conditions
- Hematological Malignancy
- Being tested
- Posaconazole prophylaxis 120 mg/m² tid, Blood sampling
- Keywords
- chemotherapy, stem cell transplantation
- Medical subject headings
- Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Posaconazole prophylaxis 120 mg/m² tidDrug
Patients are receiving posaconazole to prevent invasive fungal infections in a dose of 120 mg/m² tid
Blood samplingProcedure or surgery
During steady state treatment with posaconazole (at least 7 days), 9 blood samples are taken via a central venous catheter to evaluate the pharmacokinetics of posaconazole.
| Study group | Role | What they receive |
|---|---|---|
| Posaconazole 120mg/m² tid | Experimental | Pediatric patients admitted to receive chemotherapy or hematopoietic stem cell transplantation for the treatment of a hematological malignancy are receiving Posaconazole prophylaxis 120 mg/m² tid.
At steady state, blood sampling will be performed: 9 blood samples will be taken during 1 dosing interval to evaluate the pharmacokinetics of posaconazole. Receives: Drug: Posaconazole prophylaxis 120 mg/m² tid; Procedure: Blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
pharmacokinetic parameters of posaconazole
9 blood samples are taken during one day at steady state posaconazole plasma concentrations. The following pharmacokinetic parameters will be calculated using non-compartmental pharmacokinetic analysis: Cmax, Cmin, Tmax, Area Under the Curve during 1 dosing interval and over 24 hours, Clearance, Distribution volume, Halflife.
Measured: One day at steady state posaconazole treatment
Secondary outcomes (2)
Safety of posaconazole, focussing on nausea, vomiting and liver function abnormalities (according to the Common Terminology Criteria for Adverse Events (CTCAE classification).
Patients receiving posaconazole prophylactically are closely monitored for adverse events possibly related to the drug. They are clinically monitored for nausea, vomiting and diarrhea. Liver function abnormalities are scored according to the CTCAE classification.
Measured: patients will be followed for the duration of hospital stay, an expected average of 3-4 weeks
Efficacy: patients are monitored for breakthrough infections according the the European Organisation for Research and Treatment of Cancer- Mycoses Study Group (EORTC-MSG) criteria.
Patients receiving posaconazole prophylactically are closely monitored for the presence of an invasive fungal infection. Patients are closely followed in case an invasive fungal infection is suspected: Fever is monitored, radiography is performed and galactomannan is measured frequently. Invasive fungal infections are categorized according to the revised EORTC-MSG criteria
Measured: patients will be followed for the duration of hospital stay, an expected average of 3-4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2015 (estimated)
- Study startFeb 2012
- Primary completionAug 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematological MalignancyStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Collaborators
- Institutul Clinic Fundeni
- Responsible party
- Principal investigator, Ap.r Kim Vanstraelen, Universitaire Ziekenhuizen KU Leuven
- Investigators
- Anca Colita, MD, Principal investigator, Institutul Clinic Fundeni, Bucarest, RomaniaKim Vanstraelen, PharmD, Principal investigator, Catholic University Leuven, Leuven, Belgium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02372357
- Sponsor's protocol ID
- 2841/20 Feb 2012
- Status last verified
- Mar 2015
- First submitted
- 6 Feb 2015
- Last updated
- 3 Mar 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A New Dosing Regimen for Posaconazole Prophylaxis in Children Based in Body Surface Area
- ClinicalTrials.gov ID
- NCT02372357
- Acronym / sponsor ID
- 2841/20 Feb 2012
- Conditions
- Hematological Malignancy
- Keywords
- chemotherapy, stem cell transplantation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Collaborators
- Institutul Clinic Fundeni
- Study start
- Feb 2012
- Primary completion
- Aug 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 26 Feb 2015 (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.
A new prophylactic posaconazole dosing regimen of 120mg/m² tid is evaluated pharmacologically in children 13 years and younger, suffering from a hematologic malignancy.
Detailed description
Invasive fungal infections (IFI), especially candidiasis and aspergillosis, are a serious threat to immunocompromised pediatric patients. Because diagnosis of IFI in pediatric patients is difficult, due to the lack of specific clinical and radiological signs and the low sensitivity of blood cultures, antifungal prophylaxis would largely optimize management of IFI in this setting. However, antifungal prophylaxis remains a matter of debate, as no clear consensus has yet been reached about the optimal drug. Very limited pediatric data are available, and current guidelines are mainly based on extrapolation of adult data. Fluconazole remains the drug of choice in many centers, despite its non-mould active spectrum. Itraconazole, liposomal amphotericin B and nebulized lipid-formulations of amphotericin B are often used off-label, although neither their pharmacokinetics (PK), nor their efficacy and safety have been documented in a proper way. Voriconazole is registered for children older than 2 years of age, mainly in the treatment setting. Moreover, its extremely variable PK profile, uncertainty about adequate exposure and risk for hepatotoxicity and neurotoxicity do not favor the use of voriconazole in this setting. Finally, micafungin only has low recommendation in the prophylactic setting, due to the possible risk of liver tumours.
Posaconazole would be the ideal antifungal drug to be used prophylactically in children for many reasons. It has a broad spectrum of activity, including emerging moulds like Aspergillus spp. and Zygomycetes. It has shown to be superior over fluconazole and itraconazole in preventing IFI in adults and it has a favorable safety profile, with nausea and vomiting being the most frequently encountered adverse events. However, lack of pharmacokinetic (PK) data in children younger than 13 years of age, results in only a marginal recommendation in current guidelines [8]. Little information is available about the correct dosing regimen of the available oral suspension in young pediatric patients, and similar to what is observed in adults, often very low posaconazole plasma concentrations (PPCs) are being measured. Therefore, therapeutic drug monitoring (TDM) is recommended to reach adequate PPCs above 0.5mg/L or 0.7 mg/L followed by increasing the dose as needed.
In this study, the pharmacokinetics of a newly introduced dosing regimen for posaconazole oral suspension is investigated, based on body surface area (BSA), used prophylactically in immunocompromised children under the age of 13.
Pediatric patients, admitted to the hospital to receive chemotherapy or hematopoietic stem cell transplantation are treated prophylactically with posaconazole 120mg/m² tid.
At steady state (after at least 7 days of posaconazole treatment), 9 plasma samples are collected in these patients to calculate the area under the curve and other relevant PK parameters as maximum and minimal plasma concentrations, volume of distribution, halflife and clearance rate.
Finally, these results will be compared to adult data in literature to evaluate whether 120mg/m² tid an adequate dosing regimen in children.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Posaconazole 120mg/m² tid | Experimental | Drug: Posaconazole prophylaxis 120 mg/m² tid, Procedure: Blood samplingPediatric patients admitted to receive chemotherapy or hematopoietic stem cell transplantation for the treatment of a hematological malignancy are receiving Posaconazole prophylaxis 120 mg/m² tid. At steady state, blood sampling will be performed: 9 blood samples will be taken during 1 dosing interval to evaluate the pharmacokinetics of posaconazole. |
Who may qualify
- Ages
- 2 to 13 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 2-13 years of age
- hematological malignancy
- need for antifungal prophylaxis because of neutropenia caused by chemotherapy and/or hematopoietic stem cell transplantation.
Key exclusion criteria (2 listed)
- <2 years of age
- > 13 years of age
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 |
|---|---|---|
| Posaconazole prophylaxis 120 mg/m² tidPatients are receiving posaconazole to prevent invasive fungal infections in a dose of 120 mg/m² tid | Drug | Posaconazole 120mg/m² tid |
| Blood samplingDuring steady state treatment with posaconazole (at least 7 days), 9 blood samples are taken via a central venous catheter to evaluate the pharmacokinetics of posaconazole. | Procedure or surgery | Posaconazole 120mg/m² tid |
Primary outcome
pharmacokinetic parameters of posaconazole
Time frame: One day at steady state posaconazole treatment
9 blood samples are taken during one day at steady state posaconazole plasma concentrations. The following pharmacokinetic parameters will be calculated using non-compartmental pharmacokinetic analysis: Cmax, Cmin, Tmax, Area Under the Curve during 1 dosing interval and over 24 hours, Clearance, Distribution volume, Halflife.
2 secondary outcomes
Safety of posaconazole, focussing on nausea, vomiting and liver function abnormalities (according to the Common Terminology Criteria for Adverse Events (CTCAE classification).
Time frame: patients will be followed for the duration of hospital stay, an expected average of 3-4 weeks
Efficacy: patients are monitored for breakthrough infections according the the European Organisation for Research and Treatment of Cancer- Mycoses Study Group (EORTC-MSG) criteria.
Time frame: patients will be followed for the duration of hospital stay, an expected average of 3-4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2015.
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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.
Anca Colita, MD principal investigator
Institutul Clinic Fundeni, Bucarest, Romania
Kim Vanstraelen, PharmD principal investigator
Catholic University Leuven, Leuven, Belgium
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Posaconazole prophylaxis 120 mg/m² tid and Blood sampling in people with Hematological Malignancy, run by Universitaire Ziekenhuizen KU Leuven at 2 sites in 2 countries.
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 3 inclusion and 2 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: finished, as of the sponsor's last update on 3 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Belgium, Romania. 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 phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
pharmacokinetic parameters of posaconazole (time frame: One day at steady state posaconazole treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Mar 2015.