A Pharmacokinetic Study of Melphalan in Children

August 24, 2021 updated by: Children's Hospital Medical Center, Cincinnati

Melphalan Pharmacokinetics in Children Undergoing Hematopoietic Stem Cell Transplantation: A Pilot Study

The purpose of this study is to examine the pharmacokinetics (PK) of melphalan in children undergoing hematopoietic stem cell transplantation (HSCT). Melphalan is an important component of HSCT preparative regimens, but can be associated with significant toxicity. PK data is a powerful clinical tool that, when used to develop individualized treatment plans for a specific patient, may ultimately increase the likelihood of selecting the right dose for the right patient and/or of reducing the number of adverse drug events. The investigators' goal is to establish baseline pediatric melphalan PK data. These data may be used for patient specific dosing of melphalan in the future to minimize toxicity and improve transplant outcomes.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Hematopoietic stem cell transplantation (HSCT) continues to be the only curative therapy for patients with many hematological diseases. The adverse effects associated with chemotherapy agents used as part of HSCT preparative regimens are not insignificant and can be life threatening at times. The investigators' central hypothesis is that increased systemic exposure to melphalan due to variation in PK in younger children leads to increased toxicity seen in them. Although the PK of melphalan has been studied in animal models and in adult patients, limited data exists in pediatric patients especially those undergoing allogeneic HSCT. The objective of this study is to describe the pharmacokinetics of melphalan in children undergoing hematopoietic stem cell transplantation. Up to forty patients who are scheduled to receive melphalan as part of their preparative regimen will be enrolled. Prior to the start of the preparative regimen, study participants will receive a test dose of melphalan (10% of the standard dose). Blood samples will be collected at specific time points prior to and after the administration of the test dose and again around the full standard dose of melphalan. This study will establish that a novel method (dry blood spot assay) of determining PK of melphalan can be utilized in the clinical setting. Additionally, urine samples will be collected to measure markers of kidney injury, which will help correlate melphalan exposure with toxicity.

Study Type

Interventional

Enrollment (Actual)

34

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients undergoing either allogeneic RIC HSCT, or autologous transplant containing melphalan as part of the preparative regimen at CCHMC will be included.

Exclusion Criteria:

  • Failure to sign informed consent, or inability to undergo informed consent process.
  • It is not medically advisable to obtain the specimens necessary for this study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Melphalan in Patients Receiving HSCT

The investigators will recruit approximately 30 patients who are scheduled to undergo allogeneic transplant with reduced intensity conditioning that includes melphalan. Approximately 10 patients who will receive melphalan as part of their conditioning regimen for an autologous transplant will also be recruited.

A test dose of melphalan will be administered prior to the start of the HSCT preparative regimen. The test dose will equal 10% of the standard dose. Blood samples will be drawn for pharmacokinetic measurement prior to and after the administration of the test dose and again around the full standard dose of melphalan. Urine samples will also be collected around the test dose and full standard dose of melphalan to measure markers of kidney injury.
Drug: Melphalan
Melphalan is a bifunctional alkylating agent that inhibits DNA and RNA synthesis, cross-links strands of DNA and acts on both resting and rapidly dividing cells including tumor cells. It is administered intravenously.
Other Names:
  • Alkeran

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To characterize the pharmacokinetics of melphalan in children undergoing HSCT
Time Frame: Prior to the melphalan infusion, and then approximately 5 min, 15 min, 30 min, 45 min, 60 min, 2, 2.5, 4, and 6 hours after the end of the melphalan infusion.
Blood samples will be collected at the above time points around the test dose of melphalan and again around the standard full dose of melphalan. AUC will be used to characterize the pharmacokinetics of melphalan.
Prior to the melphalan infusion, and then approximately 5 min, 15 min, 30 min, 45 min, 60 min, 2, 2.5, 4, and 6 hours after the end of the melphalan infusion.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Perform measurement of acute kidney injury marker, KIM-1
Time Frame: Prior to the melphalan infusion and approximately 8 hours and 24 hours following the end of melphalan infusion.
Urine samples will be collected at the above time points around the test dose of melphalan and again around the standard full dose of melphalan for measurement of KIM-1.
Prior to the melphalan infusion and approximately 8 hours and 24 hours following the end of melphalan infusion.
Perform measurement of acute kidney injury marker, NGAL
Time Frame: Prior to the melphalan infusion and approximately 8 hours and 24 hours following the end of melphalan infusion.
Urine samples will be collected at the above time points around the test dose of melphalan and again around the standard full dose of melphalan for measurement of NGAL.
Prior to the melphalan infusion and approximately 8 hours and 24 hours following the end of melphalan infusion.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospital Medical Center, Cincinnati

Investigators

  • Principal Investigator: Sharat Chandra, MD, Children's Hospital Medical Center, Cincinnati

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 8, 2015

Primary Completion (Actual)

September 22, 2018

Study Completion (Actual)

September 23, 2018

Study Registration Dates

First Submitted

March 4, 2015

First Submitted That Met QC Criteria

March 11, 2015

First Posted (Estimate)

March 17, 2015

Study Record Updates

Last Update Posted (Actual)

August 30, 2021

Last Update Submitted That Met QC Criteria

August 24, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2014-5123

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Hematopoietic Stem Cell Transplantation

Clinical Trials on Melphalan

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in United Kingdom

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe