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

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

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.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease; Hemoglobinopathies; Thalassemia; Hematologic Malignancies; Immunodeficiencies; Fanconi's Anemia; Nonmalignant Diseases; Genetic Inborn Errors of Metabolism
• Intervention / Treatment: Drug: Melphalan

Detailed 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.

• Study Type: Observational
• Enrollment (Actual): 25

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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 melphalan 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 melphalan in a clinic or any other out-patient setting.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pediatric patients undergoing Hematopoietic Stem Cell Transplant; Children undergoing allogeneic hematopoietic stem cell transplant (alloHCT) at University of California, San Francisco Benioff Children's Hospital.	Drug: Melphalan; Other Names: Evomela

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2015
• Primary Completion (Actual): May 31, 2021
• Study Completion (Actual): May 31, 2021

Study Registration Dates

• First Submitted: January 5, 2018
• First Submitted That Met QC Criteria: July 24, 2018
• First Posted (Actual): August 1, 2018

Study Record Updates

• Last Update Posted (Actual): October 4, 2021
• Last Update Submitted That Met QC Criteria: September 27, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Pediatric; Pharmacokinetics; Allogeneic; Melphalan
• Additional Relevant MeSH Terms: Metabolic Diseases; Neoplasms; Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Anemia; DNA Repair-Deficiency Disorders; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Hematologic Neoplasms; Anemia, Sickle Cell; Fanconi Anemia; Thalassemia; Metabolism, Inborn Errors; Hemoglobinopathies; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Melphalan
• Other Study ID Numbers: P1517152; 150811 (Other Identifier: University of California, San Francisco)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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