A Pharmacokinetic Study of Melphalan in Children

NCT02390544 | Completed Phase 1

• 1 other identifier: 2014-5123
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Hematopoietic Stem Cell Transplantation

Keywords

children; bone marrow transplant; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• To characterize the pharmacokinetics of melphalan in children undergoing HSCT

  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 Outcomes (2)

• Perform measurement of acute kidney injury marker, 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

  Prior to the melphalan infusion and approximately 8 hours and 24 hours following the end of melphalan infusion.

Study Arms (1)

Melphalan in Patients Receiving HSCT

EXPERIMENTAL

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

Interventions

Melphalan 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.

Also known as: Alkeran

Melphalan in Patients Receiving HSCT

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Interventions

Melphalan

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Sharat Chandra, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

• Parinda Mehta, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2015
• First Posted: March 17, 2015
• Study Start: May 8, 2015
• Primary Completion: September 22, 2018
• Study Completion: September 23, 2018
• Last Updated: August 30, 2021

Record last verified: 2021-08

Locations

US (1)