Study of Melphalan Drug Exposure in Pediatric Hematopoietic Stem Cell Transplant Patients

Sickle Cell Disease Clinical Trial

Official title:

Population Pharmacokinetics (PK) of Melphalan in Pediatric Patients Undergoing Allogeneic Hematopoietic Cell Transplantation (HCT)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03609827
• Other study ID #: P1517152
• Secondary ID: 150811
• Status: Completed
• Start date: September 1, 2015
• Est. completion date: May 31, 2021

Study information

• Verified date: September 2021
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Melphalan 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 melphalan 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 individual factors cause changes in melphalan drug levels in pediatric bone marrow transplant patients and that high levels may cause severe side-effects.

Description:

Melphalan is an alkylating agent 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 pharmacokinetics (PK) study investigating the clinical pharmacology of melphalan in 24 children undergoing allogeneic hematopoietic stem cell transplant (alloHCT) at University of California, San Francisco Benioff Children's Hospital.

Patients would receive melphalan regardless of whether or not they decide to consent to PK sampling.

Melphalan 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 melphalan exposure in pediatric alloHCT recipients. Population PK methodologies support the use of sparse sampling and therefore allow us 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 melphalan drug concentrations over the duration of melphalan therapy (3 to 5 days).

To evaluate sources of variability impacting melphalan 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: May 31, 2021
• Est. primary completion date: May 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 17 Years

Eligibility

Inclusion Criteria:

• Children 0-17 years of age

• Undergoing alloHCT for the treatment of malignant or nonmalignant disorder

• Receiving melphalan-based preparative regimen

Exclusion Criteria:

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Melphalan

Locations

Country	Name	City	State
United States	University of California, San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Francisco

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of melphalan for HCT in pediatric patients.		5min post end of infusion
Primary	Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of melphalan for HCT in pediatric patients.		15 min post end of infusion
Primary	Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of melphalan for HCT in pediatric patients.		30 min post end of infusion
Primary	Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of melphalan for HCT in pediatric patients.		1 hr post end of infusion
Primary	Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of melphalan for HCT in pediatric patients.		2 hrs post end of infusion
Secondary	Evaluate the event free survival according to the AUC of melphalan		1month post transplant
Secondary	Evaluate the event free survival according to the AUC of melphalan		3 months post transplant
Secondary	Evaluate the event free survival according to the AUC of melphalan		1 year post transplant