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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
34

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Children's Hospital Medical Center, Cincinnati

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 8, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 22, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 23, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 4, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 11, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 17, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 30, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 24, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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.

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