Study of Thiotepa and TEPA Drug Exposure in Pediatric Hematopoietic Stem Cell Transplant Patients
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|ClinicalTrials.gov Identifier: NCT03609840|
Recruitment Status : Recruiting
First Posted : August 1, 2018
Last Update Posted : November 17, 2020
|Condition or disease|
|Hematologic Malignancies Nonmalignant Diseases Immune Deficiency Hemoglobinopathies Genetic Inborn Errors of Metabolism Fanconi Anemia Thalassemia Sickle Cell Disease|
Thiotepa is an alkylating agent with potent antitumor and immunosuppressive properties used in conditioning regimens of pediatric hematopoietic cell transplantation (HCT) to promote stem cell engraftment. Thiotepa is a prodrug that undergoes metabolic conversion in the liver by CYP2B6 and CYP3A4 to its primary active metabolite, TEPA.
This is a single-center, prospective, non-interventional pharmacokinetics (PK) study investigating the clinical pharmacology of thiotepa and TEPA in 60 children undergoing hematopoietic stem cell transplant (HCT) at UCSF Benioff Children's Hospital.
Patients would receive thiotepa regardless of whether or not they decide to consent to PK sampling.
Thiotepa doses will not be adjusted based on PK data. The investigators will apply the combination of a limited sampling strategy and population PK methodologies to determine specific factors influencing thiotepa and TEPA exposure in pediatric HCT recipients. Population PK methodologies support the use of sparse sampling and therefore allow the investigators to investigate drug levels in a pediatric population that would otherwise not be feasible using traditional intensive PK sampling.
Subjects will undergo PK sampling of plasma thiotepa and TEPA drug concentrations over the duration of thiotepa therapy (3 to 5 days).
To evaluate sources of variability impacting thiotepa and TEPA 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 Type :||Observational|
|Estimated Enrollment :||60 participants|
|Official Title:||Population Pharmacokinetics and Pharmacodynamics of Thiotepa and TEPA in Pediatric Patients Undergoing Hematopoietic Cell Transplantation (HCT).|
|Actual Study Start Date :||January 10, 2018|
|Estimated Primary Completion Date :||July 2021|
|Estimated Study Completion Date :||December 2021|
- Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of thiotepa 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 thiotepa for HCT in pediatric patients. [ Time Frame: 4hours post start of infusion ]
- Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of thiotepa for HCT in pediatric patients. [ Time Frame: 6 hours post start of infusion ]
- Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of thiotepa for HCT in pediatric patients. [ Time Frame: 24hours post start of infusion ]
- Evaluate the event free survival according to the AUC of thiotepa [ Time Frame: 1month post transplant ]
- Evaluate the event free survival according to the AUC of thiotepa [ Time Frame: 3 months post transplant ]
- Evaluate the event free survival according to the AUC of thiotepa [ Time Frame: 1 year post transplant ]
Biospecimen Retention: Samples With DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03609840
|Contact: Janel R Long-Boyle, PharmDfirstname.lastname@example.org|
|Contact: Chris Dvorak, MDemail@example.com|
|United States, California|
|University of California, San Francisco||Recruiting|
|San Francisco, California, United States, 94143|
|Contact: Danna Chan, PharmD 415-596-4594 firstname.lastname@example.org|
|Contact: Janel Long-Boyle, PharmD, PhD 415-514-2746 email@example.com|
|Principal Investigator: Janel Long-Boyle, PharmD, PhD|
|Principal Investigator:||Janel Long-Boyle, PharmD, PhD||University of California, San Francisco|