Study of Fludarabine Drug Exposure in Pediatric Bone Marrow Transplantation (HCT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by University of California, San Francisco
Sponsor:
Collaborator:
Thrasher Research Fund
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01316549
First received: March 14, 2011
Last updated: April 22, 2014
Last verified: April 2014
  Purpose

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.


Condition
Hematologic Malignancies
Nonmalignant Diseases
Immunodeficiencies
Hemoglobinopathies
Genetic Inborn Errors of Metabolism
Fanconi's Anemia,
Thalassemia
Sickle Cell Disease

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Population Pharmacokinetics of Fludarabine in Pediatric Patients Undergoing Hematopoietic Cell Transplantation

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Identify specific clinical markers or characteristics that impact fludarabine PK exposure. [ Time Frame: up to 100 days post transplant ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Establish the relationship between fludarabine exposure and clinical outcomes. [ Time Frame: up to 100 days post transplant ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

whole blood, DNA


Estimated Enrollment: 75
Study Start Date: September 2010
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
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 UCSF 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.

  Eligibility

Ages Eligible for Study:   up to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

The target population for the proposed study includes children 0-17 years of age undergoing alloHCT for the treatment of malignant and nonmalignant disorders.

Patients receiving fludarabine over 3 to 5 days are eligible to participate.

All patients enrolled in this study will undergo PK sampling on the inpatient pediatric BMT unit at UCSF Benioff Children's Hospital. The proposed research will not study any patients receiving fludarabine in a clinic or any other out-patient setting.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01316549

Contacts
Contact: Janel R Long-Boyle, PharmD, PhD 415-514-2746 long-boylej@pharmacy.ucsf.edu
Contact: Chris Dvorak, MD 415-476-0554 dvorakc@peds.ucsf.edu

Locations
United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Janel R Long-Boyle, PharmD, PhD    415-514-2746    long-boylej@pharmacy.ucsf.edu   
Principal Investigator: Janel R Long-Boyle, PharmD, PhD         
Sponsors and Collaborators
University of California, San Francisco
Thrasher Research Fund
Investigators
Principal Investigator: Janel R Long-Boyle, PharmD, PhD University of California, San Francisco
  More Information

No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01316549     History of Changes
Other Study ID Numbers: P0037192
Study First Received: March 14, 2011
Last Updated: April 22, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Francisco:
fludarabine
pharmacokinetics
pediatric
allogeneic
hematopoietic cell transplantation

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Anemia, Sickle Cell
Thalassemia
Fanconi Anemia
Fanconi Syndrome
Hemoglobinopathies
Metabolism, Inborn Errors
Immune System Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Genetic Diseases, Inborn
Anemia, Hypoplastic, Congenital
Anemia, Aplastic
Bone Marrow Diseases
DNA Repair-Deficiency Disorders
Metabolic Diseases
Kidney Diseases
Urologic Diseases
Renal Tubular Transport, Inborn Errors
Fludarabine
Fludarabine phosphate
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents

ClinicalTrials.gov processed this record on October 19, 2014