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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03609840
Other study ID # 17-21994
Secondary ID 17087
Status Completed
Phase
First received
Last updated
Start date May 24, 2017
Est. completion date July 31, 2023

Study information

Verified date September 2023
Source University of California, San Francisco
Contact n/a
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

Thiotepa is a chemotherapy drug used extensively in bone marrow transplantation. Thiotepa is a prodrug that undergoes metabolic conversion in the liver by CYP2B6 and CYP3A4 to its primary active metabolite, triethylene phosphoramide (TEPA). The goal of this study is to determine what causes some children to have different drug concentrations of thiotepa and TEPA 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 certain clinical and genetic factors cause changes in thiotepa and TEPA drug levels in pediatric bone marrow transplant patients and that high levels may cause severe side-effects.


Description:

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 University of California, San Francisco 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.


Recruitment information / eligibility

Status Completed
Enrollment 25
Est. completion date July 31, 2023
Est. primary completion date July 31, 2023
Accepts healthy volunteers No
Gender All
Age group N/A to 17 Years
Eligibility Inclusion Criteria: 1. be between 0 to 17 years of age; 2. meet protocol specific eligibility criteria for autologous or allogeneic HCT 3. will be receiving thiotepa as part of their conditioning regimen. Exclusion Criteria: - Any child 7-17 years of age unwilling to provide assent - Parent or guardian unwilling to provide written consent

Study Design


Intervention

Drug:
Thiotepa
Given IV

Locations

Country Name City State
United States University of California, San Francisco San Francisco California

Sponsors (1)

Lead Sponsor Collaborator
University of California, San Francisco

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of thiotepa for HCT in pediatric patients. Area-under-the-curve (AUC) will be derived from the empirical Bayes estimates of individual clearance 2 hours post start of infusion
Primary Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of thiotepa for HCT in pediatric patients. Area-under-the-curve (AUC) will be derived from the empirical Bayes estimates of individual clearance 4 hours post start of infusion
Primary Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of thiotepa for HCT in pediatric patients. Area-under-the-curve (AUC) will be derived from the empirical Bayes estimates of individual clearance 6 hours post start of infusion
Primary Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of thiotepa for HCT in pediatric patients. Area-under-the-curve (AUC) will be derived from the empirical Bayes estimates of individual clearance 24 hours post start of infusion
Secondary Event free survival according to the AUC of thiotepa Death due to any cause within 1 month post-transplant will be considered an event. 1 month post transplant
Secondary Event free survival according to the AUC of thiotepa Death due to any cause within day 3 months post-transplant will be considered an event. 3 months post transplant
Secondary Event free survival according to the AUC of thiotepa Death due to any cause within day 1 year post-transplant will be considered an event. 1 year post transplant
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