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

• ClinicalTrials.gov Identifier: NCT03609814
• Recruitment Status: Completed
• First Posted: August 1, 2018
• Last Update Posted: October 4, 2021
• Sponsor: University of California, San Francisco
• Information provided by (Responsible Party): University of California, San Francisco

Study Description

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	Intervention/treatment
Hematologic Malignancies; Nonmalignant Diseases; Immunodeficiencies; Hemoglobinopathies; Genetic Inborn Errors of Metabolism; Fanconi's Anemia; Thalassemia; Sickle Cell Disease	Drug: Clofarabine; Drug: Fludarabine Injection

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 University of California, San Francisco 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.

Study Design

• Study Type: Observational
• Actual Enrollment: 30 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)
• Actual Study Start Date: January 26, 2016
• Actual Primary Completion Date: June 30, 2020
• Actual Study Completion Date: June 30, 2020

Groups and Cohorts

Group/Cohort	Intervention/treatment
Pediatric Bone Marrow Transplantation Recipients; Children undergoing alloHCT at UCSF Benioff Children's Hospital.	Drug: Clofarabine; Given IV; Drug: Fludarabine Injection; Given IV

Outcome Measures

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

Eligibility Criteria

• 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

Contacts and Locations

Locations

United States, California

University of California, San Francisco

San Francisco, California, United States, 94143

Sponsors and Collaborators

University of California, San Francisco

Investigators

• Principal Investigator: Janel Long-Boyle, PharmD, PhD; University of California, San Francisco

More Information

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT03609814
• Other Study ID Numbers: P1518454; 19081 ( Other Identifier: University of California, San Francisco )
• First Posted: August 1, 2018
• Last Update Posted: October 4, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by University of California, San Francisco:

fludarabine; clofarabine; pharmacokinetics; pediatric; allogeneic

Additional relevant MeSH terms:

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; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Bone Marrow Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Fludarabine; Clofarabine; Antineoplastic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action