A Pharmacokinetic Study of Melphalan in Children

NCT ID: NCT02390544

Last Updated: 2021-08-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-08
• Study Completion Date: 2018-09-23

Brief Summary

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.

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.

Conditions

Hematopoietic Stem Cell Transplantation

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Melphalan

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Alkeran

Eligibility Criteria

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.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sharat Chandra, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Medical Center, Cincinnati

Parinda Mehta, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Medical Center, Cincinnati

Locations

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Countries

United States

Other Identifiers

2014-5123

Identifier Type: -

Identifier Source: org_study_id