Hematologic MalignanciesHCTNCT01316549
Study of Fludarabine Drug Exposure in Pediatric Bone Marrow Transplantation
An observational study of Hematologic Malignancies and Nonmalignant Diseases, run by University of California, San Francisco at 1 site in United States.
Trial summary
Fludarabine is a chemotherapy drug used extensively in bone marrow transplantation. The goal of this study is to determine what causes some children to have different drug concentrations of fludarabine in their bodies and if drug levels are related to whether or not a child experiences severe side-effects during their… Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- Hematologic Malignancies, Nonmalignant Diseases, Immunodeficiencies
- What is being tested?
- Fludarabine
- Type of treatment
- Injection or infusion
- How many people
- 67 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2011to 30 Apr 2016
- Phase
- Observational
- 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 Up to 17 years
- All sexes
- No healthy volunteers
- Child
Study population: The target population for the proposed study includes children 0-17 years of age undergoing alloHCT for the treatment of malignant and nonmalignant disorders. Patients receiving fludarabine over 3 to 5 days are eligible to participate. All patients enrolled in this study will undergo PK sampling on the inpatient pediatric BMT unit at UCSF Benioff Children's Hospital. The proposed research will not study any patients receiving fludarabine in a clinic or any other out-patient setting.
Who may be able to join
- Children 0-17 years of age
- Undergoing alloHCT for the treatment of malignant or nonmalignant disorder
- Receiving fludarabine-based preparative regimen
Who cannot join
- Any child 7-17 years of age unwilling to provide assent
- Parent or guardian unwilling to provide written consent
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94143
About this study
Official title: Population Pharmacokinetics of Fludarabine in Pediatric Patients Undergoing Hematopoietic Cell Transplantation
Fludarabine is a chemotherapy drug used extensively in bone marrow transplantation. The goal of this study is to determine what causes some children to have different drug concentrations of fludarabine in their bodies and if drug levels are related to whether or not a child experiences severe side-effects during their bone marrow transplant. The hypothesis is that clinical and genetic factors cause changes in fludarabine drug levels in pediatric bone marrow transplant patients and that high levels may cause severe side-effects.
Read the detailed description
Fludarabine is a nucleoside analog with potent antitumor and immunosuppressive properties used in conditioning regimens of pediatric allogeneic hematopoietic cell transplantation (alloHCT) to promote stem cell engraftment.
This is a single-center, pharmacokinetic-pharmacodynamic (PK-PD) study investigating the clinical pharmacology of fludarabine in 45 children undergoing alloHCT at University of California, San Francisco Benioff Children's Hospital.
Patients would receive fludarabine regardless of whether or not they decide to consent to PK sampling.
Fludarabine doses will not be adjusted based on PK data.
We will apply the combination of a D-optimality-based limited sampling strategy and population PK methodologies to determine specific factors influencing fludarabine exposure in pediatric alloHCT recipients and identify exposure-response relationships.
Subjects will undergo PK sampling of plasma (f-ara-a) and intracellular (f-ara-ATP) drug concentrations over the duration of fludarabine therapy (3 to 5 days).
To evaluate sources of variability impacting fludarabine exposure clinical data will be obtained from the patient's medical chart on each day of PK sampling.
A single blood draw for the collection of DNA and genotyping of single nucleotide polymorphisms of genes involved in fludarabine activation, transport or elimination will occur in all patients.
To assess exposure-response relationships neutrophil engraftment, treatment-related toxicity, and survival data will be collected through day 100 post-transplant.
- Conditions
- Hematologic Malignancies, Nonmalignant Diseases, Immunodeficiencies, Hemoglobinopathies, Genetic Inborn Errors of Metabolism, Fanconi Anemia
- Being tested
- Fludarabine
- Keywords
- fludarabine, pharmacokinetics, pediatric, allogeneic, hematopoietic cell transplantation
- Medical subject headings
- Hematologic Neoplasms, Immunologic Deficiency Syndromes, Hemoglobinopathies, Fanconi Anemia, Thalassemia, Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FludarabineDrug
Also called Fludara
Given as injection
| Study group | Role | What they receive |
|---|---|---|
| Inpatient Pediatric Bone Marrow Transplant Recipients | All patients enrolled in this study will be located on the inpatient pediatric bone marrow transplant unit at University of California, San Francisco Benioff Children's Hospital. Receives: Drug: Fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of fludarabine for HCT in pediatric patients.
Measured: 2hours post start of infusion
Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of fludarabine for HCT in pediatric patients.
Measured: 3hours post start of infusion
Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of fludarabine for HCT in pediatric patients.
Measured: 6hours post start of infusion
Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of fludarabine for HCT in pediatric patients.
Measured: 24hours post start of infusion
Secondary outcomes (3)
Event free survival according to the AUC of fludarabine
Measured: 1month post transplant
Event free survival according to the AUC of fludarabine
Measured: 3months post transplant
Event free survival according to the AUC of fludarabine
Measured: 1 year post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2011 (estimated)
- Study start1 Jan 2011
- Primary completion30 Apr 2016
- Study completion30 Apr 2016
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 Hematologic MalignanciesStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe 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
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Thrasher Research Fund
- Responsible party
- Sponsor
- Investigators
- Janel R Long-Boyle, PharmD, PhD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01316549
- Sponsor's protocol ID
- P0037192
- Other IDs
- 10081
- Acronym
- HCT
- Status last verified
- Sep 2021
- First submitted
- 14 Mar 2011
- Last updated
- 4 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ivaturi V, Dvorak CC, Chan D, Liu T, Cowan MJ, Wahlstrom J, Stricherz M, Jennissen C, Orchard PJ, Tolar J, Pai SY, Huang L, Aweeka F, Long-Boyle J. Pharmacokinetics and Model-Based Dosing to Optimize Fludarabine Therapy in Pediatric Hematopoietic Cell Transplant Recipients. Biol Blood Marrow Transplant. 2017 Oct;23(10):1701-1713. doi: 10.1016/j.bbmt.2017.06.021. Epub 2017 Jul 3.
PubMed 28684371
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Population Pharmacokinetics of Fludarabine in Pediatric Patients Undergoing Hematopoietic Cell Transplantation
- ClinicalTrials.gov ID
- NCT01316549
- Acronym / sponsor ID
- HCT / P0037192
- Conditions
- Hematologic Malignancies, Nonmalignant Diseases, Immunodeficiencies, Hemoglobinopathies, Genetic Inborn Errors of Metabolism, Fanconi Anemia
- Keywords
- fludarabine, pharmacokinetics, pediatric, allogeneic, hematopoietic cell transplantation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Thrasher Research Fund
- Study start
- 1 Jan 2011 (actual)
- Primary completion
- 30 Apr 2016 (actual)
- Study completion
- 30 Apr 2016 (actual)
- First posted
- 16 Mar 2011 (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.
Fludarabine is a chemotherapy drug used extensively in bone marrow transplantation. The goal of this study is to determine what causes some children to have different drug concentrations of fludarabine in their bodies and if drug levels are related to whether or not a child experiences severe side-effects during their bone marrow transplant. The hypothesis is that clinical and genetic factors cause changes in fludarabine drug levels in pediatric bone marrow transplant patients and that high levels may cause severe side-effects.
Detailed description
Fludarabine is a nucleoside analog with potent antitumor and immunosuppressive properties used in conditioning regimens of pediatric allogeneic hematopoietic cell transplantation (alloHCT) to promote stem cell engraftment.
This is a single-center, pharmacokinetic-pharmacodynamic (PK-PD) study investigating the clinical pharmacology of fludarabine in 45 children undergoing alloHCT at University of California, San Francisco Benioff Children's Hospital.
Patients would receive fludarabine regardless of whether or not they decide to consent to PK sampling.
Fludarabine doses will not be adjusted based on PK data.
We will apply the combination of a D-optimality-based limited sampling strategy and population PK methodologies to determine specific factors influencing fludarabine exposure in pediatric alloHCT recipients and identify exposure-response relationships.
Subjects will undergo PK sampling of plasma (f-ara-a) and intracellular (f-ara-ATP) drug concentrations over the duration of fludarabine therapy (3 to 5 days).
To evaluate sources of variability impacting fludarabine exposure clinical data will be obtained from the patient's medical chart on each day of PK sampling.
A single blood draw for the collection of DNA and genotyping of single nucleotide polymorphisms of genes involved in fludarabine activation, transport or elimination will occur in all patients.
To assess exposure-response relationships neutrophil engraftment, treatment-related toxicity, and survival data will be collected through day 100 post-transplant.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Inpatient Pediatric Bone Marrow Transplant Recipients | – | Drug: FludarabineAll patients enrolled in this study will be located on the inpatient pediatric bone marrow transplant unit at University of California, San Francisco Benioff Children's Hospital. |
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- The target population for the proposed study includes children 0-17 years of age undergoing alloHCT for the treatment of malignant and nonmalignant disorders. Patients receiving fludarabine over 3 to 5 days are eligible to participate. All patients enrolled in this study will undergo PK sampling on the inpatient pediatric BMT unit at UCSF Benioff Children's Hospital. The proposed research will not study any patients receiving fludarabine in a clinic or any other out-patient setting.
Key inclusion criteria (3 listed)
- Children 0-17 years of age
- Undergoing alloHCT for the treatment of malignant or nonmalignant disorder
- Receiving fludarabine-based preparative regimen
Key exclusion criteria (2 listed)
- Any child 7-17 years of age unwilling to provide assent
- Parent or guardian unwilling to provide written consent
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 |
|---|---|---|
| FludarabineAlso: FludaraGiven as injection | Drug | Inpatient Pediatric Bone Marrow Transplant Recipients |
Primary outcome
Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of fludarabine for HCT in pediatric patients.
Time frame: 2hours post start of infusion
Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of fludarabine for HCT in pediatric patients.
Time frame: 3hours post start of infusion
Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of fludarabine for HCT in pediatric patients.
Time frame: 6hours post start of infusion
Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of fludarabine for HCT in pediatric patients.
Time frame: 24hours post start of infusion
3 secondary outcomes
Event free survival according to the AUC of fludarabine
Time frame: 1month post transplant
Event free survival according to the AUC of fludarabine
Time frame: 3months post transplant
Event free survival according to the AUC of fludarabine
Time frame: 1 year post transplant
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 4 Oct 2021.
- Derived from this study: PubMed 28684371Ivaturi V, Dvorak CC, Chan D, Liu T, Cowan MJ, Wahlstrom J, Stricherz M, Jennissen C, Orchard PJ, Tolar J, Pai SY, Huang L, Aweeka F, Long-Boyle J. Pharmacokinetics and Model-Based Dosing to Optimize Fludarabine Therapy in Pediatric Hematopoietic Cell Transplant Recipients. Biol Blood Marrow Transplant. 2017 Oct;23(10):1701-1713. doi: 10.1016/j.bbmt.2017.06.021. Epub 2017 Jul 3.
- Individual participant dataSharing planned: No
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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.
Janel R Long-Boyle, PharmD, PhD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hematologic Malignancies and Nonmalignant Diseases, run by University of California, San Francisco at 1 site in United States.
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 4 Oct 2021. 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 United States. 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.
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?
Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of fludarabine for HCT in pediatric patients. (time frame: 2hours post start of infusion). The study lists 4 primary outcomes in all. 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 NCT01316549, 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 4 Oct 2021.