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Trial registered on ANZCTR


Registration number
ACTRN12613000861752
Ethics application status
Approved
Date submitted
25/07/2013
Date registered
5/08/2013
Date last updated
1/08/2019
Date data sharing statement initially provided
1/08/2019
Date results information initially provided
1/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Predicting and preventing leukaemia in children with Down syndrome.
Scientific title
A study of GATA-1 gene mutations to predict leukaemia in children with Down syndrome.
Secondary ID [1] 282794 0
None
Universal Trial Number (UTN)
Trial acronym
The PreP 21 Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Transient Myeloid Disorder (TMD) 289566 0
Myeloid Leukaemia of Down Syndrome (ML-DS) which includes Acute Megakaryoblastic Leukaemia (AMKL) and myelodysplasia 289567 0
Condition category
Condition code
Blood 289909 289909 0 0
Haematological diseases
Cancer 289910 289910 0 0
Leukaemia - Acute leukaemia

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
4
Target follow-up type
Years
Description of intervention(s) / exposure
The aim of the study is to better understand the relationship between GATA-1 gene mutations and development of transient myeloproliferative disorder (TMD) and myeloid leukaemia in children with Down syndrome (ML-DS), particularly acute megakaryoblastic leukaemia (AMKL). GATA-1 gene mutation analysis will be performed on genetic material extracted from blood.
A small sample of blood (about a teaspoon full) will be collected for GATA-1 gene mutation analysis. Another small sample of blood will be collected for a full blood count (FBC) for haematological assessment.

Methods and testing
Patients enroled on this protocol will be followed up by their primary clinician and study team to ensure that required blood collections are performed. The study will follow-up participants from birth or time of consent until the age of 4 years (48 months).

Blood collection timepoints are designed to coincide as much as possible with routine testing procedures required for children with Down syndrome.

Study samples and a full blood count (FBC) sample will be collected at the time of consent. Ideally this would be within the first few weeks after birth. All children with Down syndrome are eligible to participate in the study, regardless of any health issues they may have.

Participants who do not develop TMD will have blood collected at 3,6,12,18,24,36 and 48 months.

Participants who develop TMD will have additional blood collections to those stated above at 9, 30 and 42 months. These extra blood collections are required for monitoring the TMD.

Participants who develop AMKL will have blood collected for the study at diagnosis. After this they will no longer be required to have blood collected for study purposes.

Haematological evaluation of FBC will help clinicians monitor levels of red and white blood cells in participants.

Study samples for GATA-1 gene mutation analysis will be sent to a specialised lab for testing. Results of these tests will establish methods for GATA-1 gene mutation testing in future children with Down syndrome.

Primary Objectives
-to assess levels of GATA-1 gene mutations detected in children with Down syndrome found to have TMD/ML-DS.

-to identify factors that promote regression of TMD or subsequent progression to ML-DS in children with Down syndrome.

-to evaluate the true incidence of subclinical TMD and explore its relationship to the subsequent formation of AMKL.

Secondary Objectives
-to develop novel techniques that will assess GATA-1 gene mutations in non-TMD or non-AMKL populations in the future.

-to determine how the GATA-1 loss of function mutation contributes to the pre-leukaemic state.

-to assess feasibility of monitoring children with documented TMD or AMKL for minimal residual disease using GATA-1 mutation testing.

-to determine whether children with Down syndrome progressing to ML-DS can be indentified before frank leukaemia develops.
Intervention code [1] 287489 0
Not applicable
Comparator / control treatment
Not applicable - Obsevational study
Control group
Uncontrolled

Outcomes
Primary outcome [1] 289977 0
The prevalence of subclinical TMD/TMD and/or AMKL in children with Down syndrome.

This will be achieved by GATA-1 gene mutation analysis of blood collected for study purposes.



Timepoint [1] 289977 0
Between birth/consent and 4 years of age

Participants who do not develop TMD will have blood collected at 3,6,12,18,24,36 and 48 months.

Participants who develop TMD will have additional blood collections to those stated above at 9, 30 and 42 months. These extra blood collections are required for monitoring the TMD.
Primary outcome [2] 290158 0
Detection of subclinical TMD using blood collected for FBC analysis.

FBC analysis will be performed at local pathology laboratories.
Timepoint [2] 290158 0
Between birth/consent and 4 years of age

Participants who do not develop TMD will have blood collected at 3,6,12,18,24,36 and 48 months.

Participants who develop TMD will have additional blood collections to those stated above at 9, 30 and 42 months. These extra blood collections are required for monitoring the TMD.
Secondary outcome [1] 304033 0
Development of a novel GATA-1 gene mutation analysis technique as a reliable biomarker for risk of progression to TMD and/or AMKL.
Timepoint [1] 304033 0
Within the next 5 years.

Eligibility
Key inclusion criteria
This study is open to children born with Down syndrome or mosaic Down syndrome. The trial is currently open in NSW and may be extended to other states in the future.

Children up to and including the age of 2 years are eligible to enrol in the study.

Children with typical physical characteristics of Down syndrome are eligible for consent before cytogenetic confirmation of diagnosis is made.
Minimum age
0 Days
Maximum age
2 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Participants with incomplete/unsigned consent forms are excluded from the study.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 1239 0
Sydney Children's Hospital - Randwick
Recruitment hospital [2] 1240 0
Royal Hospital for Women - Randwick
Recruitment hospital [3] 1241 0
Prince of Wales Hospital - Randwick
Recruitment hospital [4] 1242 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [5] 1243 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [6] 1244 0
St George Hospital - Kogarah
Recruitment hospital [7] 1245 0
Liverpool Hospital - Liverpool
Recruitment hospital [8] 1246 0
Fairfield Hospital - Prairiewood
Recruitment hospital [9] 1247 0
Auburn Hospital & Community Health Services - Auburn
Recruitment hospital [10] 1248 0
Blacktown Hospital - Blacktown
Recruitment hospital [11] 1249 0
Nepean Hospital - Kingswood
Recruitment hospital [12] 1250 0
Canterbury Hospital - Campsie
Recruitment hospital [13] 1251 0
Bankstown-Lidcombe Hospital - Bankstown
Recruitment hospital [14] 1252 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [15] 1260 0
Maitland Hospital - Maitland
Recruitment hospital [16] 1261 0
Gosford Hospital - Gosford
Recruitment hospital [17] 1262 0
Wollongong Hospital - Wollongong
Recruitment hospital [18] 1333 0
Lismore Base Hospital - Lismore
Recruitment hospital [19] 1406 0
John Hunter Children's Hospital - New Lambton
Recruitment hospital [20] 9614 0
Bathurst Base Hospital - Bathurst
Recruitment hospital [21] 9615 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 7190 0
2031 - Randwick
Recruitment postcode(s) [2] 7191 0
2145 - Westmead
Recruitment postcode(s) [3] 7192 0
2050 - Camperdown
Recruitment postcode(s) [4] 7193 0
2217 - Kogarah
Recruitment postcode(s) [5] 7194 0
2170 - Liverpool
Recruitment postcode(s) [6] 7195 0
2176 - Prairiewood
Recruitment postcode(s) [7] 7196 0
2144 - Auburn
Recruitment postcode(s) [8] 7197 0
2148 - Blacktown
Recruitment postcode(s) [9] 7198 0
2194 - Campsie
Recruitment postcode(s) [10] 7199 0
2200 - Bankstown
Recruitment postcode(s) [11] 7200 0
2560 - Campbelltown
Recruitment postcode(s) [12] 7202 0
2320 - Maitland
Recruitment postcode(s) [13] 7203 0
2250 - Gosford
Recruitment postcode(s) [14] 7204 0
2500 - Wollongong
Recruitment postcode(s) [15] 7205 0
2480 - Lismore
Recruitment postcode(s) [16] 7206 0
2751 - Penrith
Recruitment postcode(s) [17] 7253 0
2305 - New Lambton
Recruitment postcode(s) [18] 18371 0
2795 - Bathurst

Funding & Sponsors
Funding source category [1] 287590 0
Charities/Societies/Foundations
Name [1] 287590 0
Steven Walter Children's Cancer Foundation
Address [1] 287590 0
PO Box 4610
Sylvania Waters NSW 2224
Country [1] 287590 0
Australia
Primary sponsor type
Hospital
Name
Kids Cancer Centre
Address
Kids Cancer Centre
Level 1 South
Sydney Children's Hospital
High Street
Randwick NSW 2031
Country
Australia
Secondary sponsor category [1] 286418 0
None
Name [1] 286418 0
Address [1] 286418 0
Country [1] 286418 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289558 0
Hunter New England Research Ethics and Governance Unit
Ethics committee address [1] 289558 0
Hunter New England Local Health District
Locked Bag No 1
New Lambton NSW 2305
Ethics committee country [1] 289558 0
Australia
Date submitted for ethics approval [1] 289558 0
27/03/2013
Approval date [1] 289558 0
11/06/2013
Ethics approval number [1] 289558 0
HNEHREC 13/04/17/4.07

Summary
Brief summary
The study is investigating whether patients with Down syndrome and Transient Myeloid Disorder (TMD) who are at a higher risk of developing Myeloid Leukaemia of Down syndrome (ML-DS), including Acute MegaKaryoblastic Leukaemia (AMKL) can be identified through prospective GATA-1 gene mutation testing.

Who is it for?
This study is open to children born with Down syndrome or mosaic Down syndrome who are up to 2 years of age. The trial is currently open in NSW and may be extended to other states in the future.
Children with typical physical characteristics of Down syndrome are eligible for consent before cytogenetic confirmation of diagnosis is made.


Trial details
Participants in this trial will be observed from birth/consent up to until 4 years of age in order to assess the levels of GATA-1 gene mutations and their association with subsequent progression to TMD and/or AMKL.

Blood collection requirements
Observation for signs of potential progression to TMD and/or AMKL will be performed by analysis of periodic full blood counts (FBC). The FBC will be assessed at local laboratories.

Blood collected for study purposes will be stored at a tumour bank. The sample will be studied for GATA-1 gene mutations. It is hoped that results from the study of GATA-1 gene mutations will be used to develop a test that will in the future help predict which children with Down syndrome are more at risk of developing AMKL (acute megakaryoblastic leukaemia).

Participants who do not develop TMD will have blood collected at 3,6,12,18,24,36 and 48 months.

Participants who develop TMD will have additional blood collections to those stated above at 9, 30 and 42 months. These extra blood collections are required for monitoring the TMD.
Participants who develop AMKL will have a final blood collection for study purposes at time of AMKL diagnosis. Blood collection for study purposes will cease at this point.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 41278 0
Prof Glenn Marshall
Address 41278 0
Kids Cancer Centre
Level 1 South
Sydney Children's Hospital
High Street
Randwick NSW 2031
Country 41278 0
Australia
Phone 41278 0
+61 2 9382 1721
Fax 41278 0
+61 2 9382 1789
Email 41278 0
g.marshall@unsw.edu.au
Contact person for public queries
Name 41279 0
Ms Sally Byatt
Address 41279 0
Kids Cancer Centre
Level 1 South
Sydney Children's Hospital
High Street
Randwick NSW 2031
Country 41279 0
Australia
Phone 41279 0
+61 410 346 294
Fax 41279 0
+61 2 9382 1789
Email 41279 0
sallyanne.byatt@health.nsw.gov.au
Contact person for scientific queries
Name 41280 0
Prof Glenn Marshall
Address 41280 0
Kids Cancer Centre
Level 1 South
Sydney Children's Hospital
High Street
Randwick NSW 2031

Country 41280 0
Australia
Phone 41280 0
+61 2 9382 1721
Fax 41280 0
Email 41280 0
g.marshall@unsw.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
There will be no IPD sharing.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary