Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000227392
Ethics application status
Approved
Date submitted
30/01/2017
Date registered
13/02/2017
Date last updated
8/01/2019
Date data sharing statement initially provided
8/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Analysis of Total Busulfan Exposure for Once Daily Intravenous Dosing in Paediatric Haematopoietic Stem Cell Transplantation- An ANZCHOG Pilot Study
Scientific title
Bu4Day-PK-2016: Analysis of Total Busulfan Exposure for Once Daily Intravenous Dosing in Paediatric Haematopoietic Stem Cell Transplantation- An ANZCHOG Pilot Study
Secondary ID [1] 291031 0
Nil known
Universal Trial Number (UTN)
U1111-1192-2087
Trial acronym
Bu4Day-PK-2016
Linked study record
Nil known

Health condition
Health condition(s) or problem(s) studied:
Haematopoietic Stem Cell Transplant 301819 0
Condition category
Condition code
Cancer 301498 301498 0 0
Children's - Other

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
For study purposes the following tests are required, which may or may not be taken as part of the institutional protocol:
1 x blood sample for pharmacogenomic screening immediately prior to first dose of intravenous Busulfan.
7 x blood samples for measurement of busulfan concentrations to be taken after each daily administration of busulfan (total 28 blood samples over 4 days per patient). Blood samples will begin with the first scheduled dose and be taken after each of the four consecutive days.
Intervention code [1] 297001 0
Not applicable
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 300887 0
Busulfan total exposure following consecutive once daily intravenous dosing in paediatric patients undergoing haematopoietic stem cell transplantation (HSCT).
Timepoint [1] 300887 0
For each dose administered blood tests will be taken prior to dose (Hr 0), immediately following dose administration completion (Hr 3), Hr 3.25, Hr 4, Hr 5, Hr 6 and Hr 8.
Primary outcome [2] 300888 0
To describe the pharmacokinetics of intravenous once daily busulfan in paediatrics over four consecutive doses including Clearance and Volume of Distribution.
Timepoint [2] 300888 0
For each dose administered blood tests will be taken prior to dose (Hr 0), immediately following dose administration completion (Hr 3), Hr 3.25, Hr 4, Hr 5, Hr 6 and Hr 8.
Secondary outcome [1] 331126 0
Exploratory outcome: expression of genes related to the metabolic clearance of busulfan treatment.
Timepoint [1] 331126 0
Pharmacogenomic blood sample at Hr 0 prior to the first dose of busulfan.
Secondary outcome [2] 331393 0
The impact of cumulative busulfan exposure (cumulative AUC) on the incidence of GVHD by review of medical records. .
Timepoint [2] 331393 0
For each dose administered blood tests will be taken prior to dose (Hr 0), immediately following dose administration completion (Hr 3), Hr 3.25, Hr 4, Hr 5, Hr 6 and Hr 8. Transplant outcome measures will be assessed at Day +30, Day +100 and Day +365 post HSCT.
Secondary outcome [3] 331394 0
The impact of cumulative busulfan exposure (cumulative AUC) on engraftment by review of medical records. .
Timepoint [3] 331394 0
For each dose administered blood tests will be taken prior to dose (Hr 0), immediately following dose administration completion (Hr 3), Hr 3.25, Hr 4, Hr 5, Hr 6 and Hr 8. Transplant outcome measures will be assessed at Day +30, Day +100 and Day +365 post HSCT.
Secondary outcome [4] 331395 0
The impact of cumulative busulfan exposure (cumulative AUC) on the incidence of transplant toxicities including Hepatic Sinuosidal Obstructtive Syndrome by review of medical records. .
Timepoint [4] 331395 0
For each dose administered blood tests will be taken prior to dose (Hr 0), immediately following dose administration completion (Hr 3), Hr 3.25, Hr 4, Hr 5, Hr 6 and Hr 8. Transplant outcome measures will be assessed at Day +30, Day +100 and Day +365 post HSCT.
Secondary outcome [5] 331396 0
The impact of cumulative busulfan exposure (cumulative AUC) on survival by review of medical records. .
Timepoint [5] 331396 0
For each dose administered blood tests will be taken prior to dose (Hr 0), immediately following dose administration completion (Hr 3), Hr 3.25, Hr 4, Hr 5, Hr 6 and Hr 8. Transplant outcome measures will be assessed at Day +30, Day +100 and Day +365 post HSCT.

Eligibility
Key inclusion criteria
Patients equal to or less than 18 years of age, with underlying disease with recognised HSCT indication who are receiving once daily IV busulfan as a component of their HSCT conditioning regimen and have adequate central venous access for blood sampling.
Minimum age
No limit
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who are unable to comply with the requirements of this study.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Descriptive statistics.
Pharmacokinetic modelling

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
3/04/2017
Actual
29/05/2017
Date of last participant enrolment
Anticipated
6/04/2020
Actual
Date of last data collection
Anticipated
5/04/2021
Actual
Sample size
Target
100
Accrual to date
18
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 7395 0
Lady Cilento Children's Hospital - South Brisbane
Recruitment hospital [2] 9819 0
Princess Margaret Hospital - Subiaco
Recruitment hospital [3] 12832 0
Sydney Children's Hospital - Randwick
Recruitment postcode(s) [1] 15192 0
4101 - South Brisbane
Recruitment postcode(s) [2] 18600 0
6008 - Subiaco
Recruitment postcode(s) [3] 25301 0
2031 - Randwick
Recruitment outside Australia
Country [1] 21168 0
New Zealand
State/province [1] 21168 0
Auckland

Funding & Sponsors
Funding source category [1] 295457 0
Other Collaborative groups
Name [1] 295457 0
Australia and New Zealand Children's Haematology and Oncology Group
Country [1] 295457 0
Australia
Funding source category [2] 301565 0
Government body
Name [2] 301565 0
Queensland Health- SERTA Grant
Country [2] 301565 0
Australia
Funding source category [3] 301566 0
University
Name [3] 301566 0
University of Queensland
Country [3] 301566 0
Australia
Primary sponsor type
Individual
Name
Rachael Lawson
Address
Lady Cilento Childrens Hospital
501 Stanley street
South Brisbane
QLD, 4101
Country
Australia
Secondary sponsor category [1] 294280 0
None
Name [1] 294280 0
None
Address [1] 294280 0
None
Country [1] 294280 0
Other collaborator category [1] 279410 0
University
Name [1] 279410 0
University of Queensland
Address [1] 279410 0
St Lucia
Queensland 4072
Country [1] 279410 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296788 0
Children's Health Queensland Hospital and Health Service Human Research Ethics Committee
Ethics committee address [1] 296788 0
Level 7, Centre for Children's Health Research
Lady Cilento Children's Hospital Precinct
62 Graham Street, South Brisbane, QLD, 4101
Ethics committee country [1] 296788 0
Australia
Date submitted for ethics approval [1] 296788 0
09/12/2016
Approval date [1] 296788 0
22/12/2016
Ethics approval number [1] 296788 0
HREC/16/QRCH/388
Ethics committee name [2] 299424 0
Child and Adolescent Health Service Human Research Ethics Committee
Ethics committee address [2] 299424 0
Princess Margaret Hospital
Corner Roberts Road and Hamilton Street
Ethics committee country [2] 299424 0
Australia
Date submitted for ethics approval [2] 299424 0
16/11/2017
Approval date [2] 299424 0
27/11/2017
Ethics approval number [2] 299424 0
RGS0000000497

Summary
Brief summary
The aim of this study is to analyse cumulative exposure, pharmacokinetics and pharmacogenomics of daily intravenous busulfan in paediatric haematopoietic stem cell transplantation.

Who is it for?
You may be eligible to join this study if you are aged 18 years or below, with underlying disease with recognised HSCT indication and are receiving once daily IV busulfan as a component of HSCT conditioning regimen and have adequate central venous access for blood sampling.

Study details
This study will involve a prospective nonrandomised trial where patients who consent be asked to provide small volumes (7 ml per day, in total 28mL from 28 samples over four days) of blood which will be sent to a central laboratory for analysis. These sample results will be used for study purposes only and will be taken in conjunction with those taken for standard of care per the institutions current practice. Transplant outcome data will be attained at day +30, +100 and +365 post transplant. The blood sample results will not interfere and will not be available to guide clinical treatment of participating patients, however will improve dose optimisation of busulfan in future patients.

This study will help guide optimal dosing regimens and reduce toxicity for paediatric patients who require intravenous busulfan as part of a HSCT regime.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 72062 0
Ms Rachael Lawson
Address 72062 0
Pharmacy Department
Lady Cilento Childrens Hospital
501 Stanley street, South Brisbane
QLD, 4101
Country 72062 0
Australia
Phone 72062 0
+61 7 3068 1900
Fax 72062 0
Email 72062 0
[email protected]
Contact person for public queries
Name 72063 0
Ms Rachael Lawson
Address 72063 0
Pharmacy Department
Lady Cilento Childrens Hospital
501 Stanley street, South Brisbane
QLD, 4101
Country 72063 0
Australia
Phone 72063 0
+61 7 3068 1900
Fax 72063 0
Email 72063 0
[email protected]
Contact person for scientific queries
Name 72064 0
Ms Rachael Lawson
Address 72064 0
Pharmacy Department
Lady Cilento Childrens Hospital
501 Stanley street, South Brisbane
QLD, 4101
Country 72064 0
Australia
Phone 72064 0
+61 7 3068 1900
Fax 72064 0
Email 72064 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.