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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

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

Intervention / Treatment
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* Drug: Melphalan


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pediatric patients undergoing Hematopoietic Stem Cell Transplant<br>Children undergoing allogeneic hematopoietic stem cell transplant (alloHCT) at University of California, San Francisco Benioff Children's Hospital. | Drug: Melphalan<br> <br> * Other names: Evomela;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analysis of the Area under the Plasma Concentration versus Time Curve (AUC) of melphalan for HCT in pediatric patients. |  | 5min post end of infusion | 
| 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 | 
| 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 | 
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the event free survival according to the AUC of melphalan |  | 1month post transplant | 
| Evaluate the event free survival according to the AUC of melphalan |  | 3 months post transplant | 
| Evaluate the event free survival according to the AUC of melphalan |  | 1 year post transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Melphalan, Pharmacokinetics, Pediatric, Allogeneic