Busulfan Pharmacokinetic Analysis, Busulfan Dosing, Hematopoietic Stem Cell Transplant (HSCT), Busulfan, Glutathione
Conditions
Keywords
Hematopoietic Stem Cell Transplant, Busulfan, Busulfan Dosing, Body Surface Area, glutathione
Brief summary
The goal of this pilot study is to determine if scaling the first busulfan dose to Body Surface Area (BSA) in children with a BSA ≥0.5 m2 and using a BSA-banded dosing table for infants (BSA \<0.5 m2) increases the fraction of patients achieving a therapeutic drug exposure after the first dose.
Detailed description
Busulfan is a drug used in conditioning regimens for bone marrow transplantation. Busulfan levels outside the desired range can cause excessive side effects or failure of bone marrow engraftment. The initial dose of busulfan is currently scaled to body weight; on subsequent days the dose may be adjusted to achieve busulfan levels in a therapeutic range. However, only half of children receiving a busulfan dose scaled to body weight achieve therapeutic blood levels after the first dose. We performed computer simulations of alternative dosing methods for infants and children, and identified that dosing based on body surface area (BSA) could significantly increase the number of children achieving therapeutic blood levels after the first dose. This study will test whether this new dosing method results in a higher percentage of patients achieving the desired busulfan blood levels after the first dose. The study will enroll up to 38 children receiving high doses of busulfan as part of their standard conditioning regimen prior to bone marrow transplant. We will use the busulfan blood levels that are routinely measured after the first dose to determine the effectiveness of our new dosing method.
Interventions
DRUGBusulfan (BU)
Busulfan is a cell cycle non-specific alkylating agent which is approved by the Food and Drug Administration (FDA) and is commercially available.
Sponsors
Children's Hospital of Philadelphia
Alex's Lemonade Stand Foundation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 21 Years
Healthy volunteers
No
Inclusion criteria
1. Subject age: ≤21 years 2. Body Surface Area (BSA): 1. Group A: BSA ≥0.5 m2 2. Group B: BSA \<0.5 m2 3. Planned for once-daily busulfan-containing conditioning regimen pre-bone marrow transplant 4. Scheduled to have TDM after the first dose of busulfan 5. Diagnosis: both benign and malignant conditions are eligible
Exclusion criteria
1\. At the time of enrollment, patients may not receive medications that significantly alter busulfan clearance, as specified below. a. If patients had received the drugs listed below prior to enrollment, the following washout periods, based on ≥ 6 times drug t½, are required. Deferasirox: ≥7 days Metronidazole: ≥7 days Ketoconazole, voriconazole: ≥7 days Itraconazole, posaconazole: ≥14 days Phenytoin: ≥21 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants who achieve a therapeutic drug exposure after the first dose of Busulfan | 1 day | Dosing for patients in Group A (BSA \>=0.5m2) will be scaled to Body Surface Area, and patients in Group B (BSA \<0.5m2) will be dosed based on the infant dosing table for Day 1 dose. The value range for therapeutic drug exposure is 36,000 μM/min (Lower Bound) - 6,000 μM/min (Upper Bound) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with sinusoidal obstruction | 100 days post transplant | Target adverse events (SOS, engraftment failure) will be tracked in all patients for the first 100 days post-transplant. |
| Number of participants with engraftment failure | 100 days post transplant | Target adverse events (SOS, engraftment failure) will be tracked in all patients for the first 100 days post-transplant. |
| Glutathione sample concentration over the 4-day course of busulfan administration. | 4 days | Plasma glutathione samples will be obtained daily to determine glutathione concentration over the 4 days busulfan is administered. A 4-day total of gluathione sample concentration will be reported. |
Countries
United States
Contacts
CONTACTMeghan Donnelly, MPH
CONTACTRuchi Singh, PhD
Outcome results
None listed