for people ages up to 17 years (full criteria)
at San Francisco, California
study started
estimated completion
Principal Investigator
by Janel Long-Boyle, PharmD, PhD
Headshot of Janel Long-Boyle
Janel Long-Boyle



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.

Official Title

Population Pharmacokinetics and Pharmacodynamics of Thiotepa and TEPA in Pediatric Patients Undergoing Hematopoietic Cell Transplantation (HCT).


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.


Hematologic Malignancies, Nonmalignant Diseases, Immune Deficiency, Hemoglobinopathies, Genetic Inborn Errors of Metabolism, Fanconi Anemia, Thalassemia, Sickle Cell Disease, Thiotepa, TEPA, Pediatric, Hematopoietic, Transplant, Hematologic Neoplasms, Sickle Cell Anemia, Inborn Errors Metabolism, Immunologic Deficiency Syndromes, Alkylating Antineoplastic Agents, Antineoplastic Agents, Pediatric Hematopoietic Stem Cell Transplant Recipients


You can join if…

Open to people ages up to 17 years

  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.

You CAN'T join if...

  • Any child 7-17 years of age unwilling to provide assent
  • Parent or guardian unwilling to provide written consent


  • UCSF
    San Francisco California 94143 United States

Lead Scientist at UCSF

  • Janel Long-Boyle, PharmD, PhD
    Dr. Boyle is a translational scientist with research interests that include pediatric cancer therapeutics, pharmacokinetics, pharmacodynamics, pharmacogenomics, and clinical trial design.


in progress, not accepting new patients
Start Date
Completion Date
University of California, San Francisco
Study Type
About 25 people participating
Last Updated