Study of Thiotepa and TEPA Drug Exposure in Pediatric Hematopoietic Stem Cell Transplant Patients
| Status: | Recruiting |
|---|---|
| Conditions: | Other Indications, Blood Cancer, Infectious Disease, HIV / AIDS, Anemia, Anemia, Hematology |
| Therapuetic Areas: | Hematology, Immunology / Infectious Diseases, Oncology, Other |
| Healthy: | No |
| Age Range: | Any - 17 |
| Updated: | 8/3/2018 |
| Start Date: | January 10, 2018 |
| End Date: | July 2020 |
| Contact: | Danna Chan, PharmD |
| Email: | danna.chan@ucsf.edu |
| Phone: | 415-596-4594 |
Population Pharmacokinetics and Pharmacodynamics of Thiotepa and TEPA in Pediatric Patients Undergoing Hematopoietic Cell Transplantation (HCT).
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, 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.
a prodrug that undergoes metabolic conversion in the liver by CYP2B6 and CYP3A4 to its
primary active metabolite, 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.
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.
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.
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
We found this trial at
1
site
San Francisco, California 94143
Principal Investigator: Janel Long-Boyle, PharmD, PhD
Phone: 415-596-4594
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