Clinical trial NCT02390544: A Pharmacokinetic Study of Melphalan in Children
Official title: Melphalan Pharmacokinetics in Children Undergoing Hematopoietic Stem Cell Transplantation: A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hematopoietic Stem Cell Transplantation
Keywords: children
bone marrow transplant
pharmacokinetics
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
First posted: 2015-03-17
Enrollment: 34
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: To characterize the pharmacokinetics of melphalan in children undergoing HSCT
timeFrame: 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:
measure: Perform measurement of acute kidney injury marker, KIM-1
timeFrame: Prior to the melphalan infusion and approximately 8 hours and 24 hours following the end of melphalan infusion.
measure: Perform measurement of acute kidney injury marker, NGAL
timeFrame: Prior to the melphalan infusion and approximately 8 hours and 24 hours following the end of melphalan infusion.
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Sharat Chandra, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Medical Center, Cincinnati
name: Parinda Mehta, MD
role: PRINCIPAL_INVESTIGATOR
References: