Study of Fludarabine Drug Exposure in Pediatric Bone Marrow Transplantation

NCT ID: NCT01316549

Last Updated: 2021-10-04

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 67 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2011-01-01
• Study Completion Date: 2016-04-30

Brief 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 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.

Conditions

Hematologic Malignancies; Nonmalignant Diseases; Immunodeficiencies; Hemoglobinopathies; Genetic Inborn Errors of Metabolism; Fanconi Anemia; Thalassemia; Sickle Cell Disease

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

Fludarabine

Intervention Type: DRUG

Given as injection

Interventions

Fludarabine

Given as injection

Intervention Type: DRUG

Other Intervention Names

Fludara

Eligibility Criteria

Inclusion Criteria

• Children 0-17 years of age
• Undergoing alloHCT for the treatment of malignant or nonmalignant disorder
• Receiving fludarabine-based preparative regimen

Exclusion Criteria

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

• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Thrasher Research Fund

OTHER

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janel R Long-Boyle, PharmD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

University of California, San Francisco

San Francisco, California, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 28684371 (View on PubMed)

Other Identifiers

10081

Identifier Type: OTHER

Identifier Source: secondary_id

P0037192

Identifier Type: -

Identifier Source: org_study_id