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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03609814
Recruitment Status : Active, not recruiting
First Posted : August 1, 2018
Last Update Posted : February 27, 2020
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco

Brief Summary:
Fludarabine and clofarabine are chemotherapy drugs used extensively in bone marrow transplantation. The goal of this study is to determine what causes some children to have different drug concentrations of clofarabine and 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 individual factors cause changes in clofarabine and fludarabine drug levels in pediatric bone marrow transplant patients and that high levels may cause severe side-effects.

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

Detailed Description:

Fludarabine and clofarabine are nucleoside analogs 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, prospective, non-interventional pharmacokinetic (PK) study investigating the clinical pharmacology of combination nucleoside analogue therapy in 24 children undergoing alloHCT at UCSF Benioff Children's Hospital.

Patients would receive clofarabine and fludarabine regardless of whether or not they decide to consent to PK sampling.

Clofarabine and fludarabine 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 clofarabine and fludarabine exposure in pediatric alloHCT recipients and identify exposure-response relationships.

Subjects will undergo PK sampling of clofarabine and fludarabine drug concentrations over the duration of combination therapy (3 to 5 days).

To evaluate sources of variability impacting clofarabine and fludarabine exposure clinical data will be obtained from the patient's medical chart on each day of PK sampling.

To assess exposure-response relationships neutrophil engraftment, treatment-related toxicity, and survival data will be collected through day 100 post-transplant.

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Study Type : Observational
Actual Enrollment : 42 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: Population Pharmacokinetics of the Nucleoside Analogues Clofarabine and Fludarabine in Pediatric Patients Undergoing Hematopoietic Cell Transplantation (alloHCT)
Study Start Date : February 2016
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : December 2020





Primary Outcome Measures :
  1. Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of fludarabine and clofarabine dual therapy for HCT in pediatric patients. [ Time Frame: 2hours post start on infusion ]
  2. Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of fludarabine and clofarabine dual therapy for HCT in pediatric patients. [ Time Frame: 3hours post start of infusion ]
  3. Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of fludarabine and clofarabine dual therapy for HCT in pediatric patients. [ Time Frame: 6hours post start of infusion ]
  4. Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of fludarabine and clofarabine dual therapy for HCT in pediatric patients. [ Time Frame: 24hours post start of infusion ]

Secondary Outcome Measures :
  1. Evaluate the event free survival according to the AUC of fludarabine and clofarabine dual therapy [ Time Frame: 1month post transplant ]
  2. Evaluate the event free survival according to the AUC of fludarabine and clofarabine dual therapy [ Time Frame: 3 months post transplant ]
  3. Evaluate the event free survival according to the AUC of fludarabine and clofarabine dual therapy [ Time Frame: 1 year post transplant ]

Biospecimen Retention:   Samples With DNA
Plasma


Information from the National Library of Medicine

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Ages Eligible for Study:   up to 17 Years   (Child)
Sexes Eligible for Study:   All
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 clofarabine and 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 clofarabine and 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 clofarabine and fludarabine-based preparative regimen

Exclusion Criteria:

  • Any child 7-17 years of age unwilling to provide assent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03609814


Locations
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United States, California
University of California, San Francisco
San Francisco, California, United States, 94143
Sponsors and Collaborators
University of California, San Francisco
Investigators
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Principal Investigator: Janel Long-Boyle, PharmD, PhD University of California, San Francisco
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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03609814    
Other Study ID Numbers: P1518454
First Posted: August 1, 2018    Key Record Dates
Last Update Posted: February 27, 2020
Last Verified: February 2020
Keywords provided by University of California, San Francisco:
fludarabine
clofarabine
pharmacokinetics
pediatric
allogeneic
Additional relevant MeSH terms:
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Hematologic Neoplasms
Anemia, Sickle Cell
Thalassemia
Fanconi Anemia
Hemoglobinopathies
Metabolism, Inborn Errors
Neoplasms
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Genetic Diseases, Inborn
Neoplasms by Site
Anemia, Hypoplastic, Congenital
Anemia, Aplastic
Bone Marrow Diseases
DNA Repair-Deficiency Disorders
Metabolic Diseases