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Trial registered on ANZCTR


Registration number
ACTRN12618000362291
Ethics application status
Approved
Date submitted
4/12/2017
Date registered
9/03/2018
Date last updated
9/03/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Determination of Calreticulin (CALR) mutation status based on peripheral blood immunohistochemistry and flow cytometry.
Scientific title
Determination of CALR mutation status based on peripheral blood immunohistochemistry and flow cytometry in patients with myeloproliferative neoplasms.
Secondary ID [1] 293525 0
Nil known
Universal Trial Number (UTN)
U1111-1206-1664
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myeloproliferative Neoplasms 305715 0
Condition category
Condition code
Blood 304931 304931 0 0
Haematological diseases
Cancer 305756 305756 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The two new methods being investigated are:
1) Flow cytometry using a fluorochrome conjugated to a CALR antibody on peripheral blood
2) Immunohistochemistry using a CALR immunostain on peripheral clotted blood.

An extra 10mL volume of blood will be collected during routine venesection undertaken as part of routine care with the participant's treating haematologist. This sample will then be split with part used for flow cytometric analysis and the remainder for immunohistochemistry.

This will only be performed a single time on a single blood sample, and there will be no followup testing or review required of the participant.
Intervention code [1] 299759 0
Diagnosis / Prognosis
Comparator / control treatment
The comparator would be the current gold standard, molecular testing for CALR mutations. This can be done either via sanger sequencing or next generation (massively parallel) sequencing. Different methods are used by different institutions, and both will be viewed as equivalent for the purpose of this study when compared to the investigational methods.
Control group
Active

Outcomes
Primary outcome [1] 304124 0
To determine whether CALR mutation status can be determined via immunohistochemistry or flow cytometric analysis of peripheral blood in a patient with known CALR mutation identified on previous molecular testing.

This will be assessed by comparing results of flow cytometric or immunohistochemical testing with molecular sequencing results (the gold standard).
Timepoint [1] 304124 0
Testing on individual samples will be done only once at time of sample collection.
Primary outcome [2] 304829 0
Determine the sensitivity and specificity of these assays for detecting CALR mutations on a small cohort of known positive and negative participants.

In detail, a range of specific cut offs for flow cytometric fluorescence or immunohistochemical positivity will have their sensitivity and specificity assessed by judging results in comparison to the gold standard, molecular sequencing. Ideally a final cut off will be chosen at which all positive results as judged by the gold standard are above the cutoff, without an excess of negative samples also being above the cut off at the same time.

This process of adjustment is a key part of the project and specific cut offs will not be provided prior to commencement.
Timepoint [2] 304829 0
Testing on individual samples will be done only once at time of sample collection.
Secondary outcome [1] 341037 0
To determine the cost and feasibility of performing this new assay, specifically in terms of cost of reagents as well as cost of scientific staff time both in preparation and analysis of samples.

This will be compared to the charge applied for molecular testing by external laboratories.
Timepoint [1] 341037 0
At completion of collection of cohort of samples, anticipated to be late 2018.

Eligibility
Key inclusion criteria
Known Myeloproliferative Disorder
Molecular Testing for JAK2 or MPL or CALR mutation previously performed
Cases: CALR positive
Controls: CALR negative OR JAK2 positive OR MPL positive
Undergoing regular blood tests as a patient of St Vincent’s Hospital Haematology Service
Willingness to provide written consent and participate in the study.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients with a history of a psychological illness or condition such as to interfere with the patient’s ability to understand the requirements of the study or to consent.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Not applicable.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Not applicable.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The CALR mutation is a new and so far rare mutation. We optimistically anticipate we may be able to identify a dozen positive cases in our service, and have set a target of 10 cases with a similar number of controls with that in mind. Given the small numbers, only basic statistical analysis is planned (e.g. sensitivity, specificity etc.… using molecular testing as the gold standard). Agreement between the new assays and molecular testing will be assessed with Cohen’s Kappa coefficient.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
9/11/2017
Date of last participant enrolment
Anticipated
31/12/2018
Actual
Date of last data collection
Anticipated
31/01/2019
Actual
Sample size
Target
20
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 9481 0
St Vincent's Private Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 18217 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 298136 0
Commercial sector/Industry
Name [1] 298136 0
Sydpath (St Vincent's Pathology)
Country [1] 298136 0
Australia
Primary sponsor type
Individual
Name
Dr Andrew Parker
Address
Sydpath, Level 5, Xavier Building, St Vincent's Hospital, 390 Victoria St, Darlinghurst, NSW, 2010.
Country
Australia
Secondary sponsor category [1] 297221 0
None
Name [1] 297221 0
No
Address [1] 297221 0
Country [1] 297221 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299156 0
St Vincent's Hospital Sydney Human Research Ethics Committee (HREC)
Ethics committee address [1] 299156 0
St Vincent's Hospital, 390 Victoria St, Darlinghurst, NSW 2010.
Ethics committee country [1] 299156 0
Australia
Date submitted for ethics approval [1] 299156 0
07/09/2016
Approval date [1] 299156 0
14/09/2016
Ethics approval number [1] 299156 0
LNR/16/SVH/230

Summary
Brief summary
The purpose of this study is to determine if new blood testing methods are effective in determining Calreticulin mutation status.

Who is it for?

You may be eligible for this study if you are over the age of 18, have a known myeloproliferative disorder and are currently undergoing regular blood tests at St Vincent’s Hospital.

Study details

Participants will continue to undergo regular testing by clinicians. However, an additional 10mL of blood will be collected during your routine venesection. This sample will then be tested for Calreticulin mutation using both of the following tests:
1. Flow cytometry
2. Immunohistochemistry
The results will then be compared to results from the current gold standard method used for testing for Calreticulin mutations.

It is hoped that results from this study would allow testing for Calreticulin mutation to be done rapidly, locally and non-invasively.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 79486 0
Dr Andrew Parker
Address 79486 0
Anatomical Pathology, Level 5, Xavier Building, St Vincent's Hospital, 390 Victoria St Darlinghurst, NSW, 2010
Country 79486 0
Australia
Phone 79486 0
+61 2 8382 9216
Fax 79486 0
Email 79486 0
[email protected]
Contact person for public queries
Name 79487 0
Dr Charles Shuttleworth
Address 79487 0
Haematology, Level 5, Xavier Building, St Vincent's Hospital, 390 Victoria St Darlinghurst, NSW 2010
Country 79487 0
Australia
Phone 79487 0
+61416425227
Fax 79487 0
Email 79487 0
[email protected]
Contact person for scientific queries
Name 79488 0
Dr Charles Shuttleworth
Address 79488 0
Haematology, Level 5, Xavier Building, St Vincent's Hospital, 390 Victoria St Darlinghurst, NSW 2010
Country 79488 0
Australia
Phone 79488 0
+61416425227
Fax 79488 0
Email 79488 0
[email protected]

No information has been provided regarding IPD availability


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.