Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616001613493
Ethics application status
Approved
Date submitted
15/11/2016
Date registered
22/11/2016
Date last updated
22/11/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
A Prospective Multi-Centre Trial Validating Flow Cytometric Minimal Residual Disease (Mrd) Pre And Post Allograft For Acute Myeloid Leukaemia (AML)
Scientific title
A Prospective Multi-Centre Trial Validating Flow Cytometric Minimal Residual Disease (Mrd) Pre And Post Allograft For Acute Myeloid Leukaemia (AML)
Secondary ID [1] 290538 0
None
Universal Trial Number (UTN)
U1111-1189-8757
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukaemia 300966 0
Condition category
Condition code
Cancer 300768 300768 0 0
Leukaemia - Acute leukaemia

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Patients with acute myeloid leukaemia (AML) who have had an allograft will be eligible for this trial. Minimal residual disease (MRD), performed by flow cytometry will be assessed at 1 month pre-allograft and 1, 3 and 6 months post-allograft. MRD is residual leukaemia that is undetectable by conventional microscopy. Our current “gold-standard” for identifying disease is based on microscopy. However, several studies have demonstrated the presence of MRD by immunological methods using a flow cytometer is predictive of relapse and overall survival. Flow cytometry (FCM) is a test where protein expression is tested on or within leukaemic cells.
The primary endpoint is to compare, in a prospective setting, the time to morphological relapse (TTMR) between patients who are MRD+ at that time point, and those who are MRD- at that time point. The cut-off values for MRD positivity is 0.1% ie. our detection sensitivity threshold is validated to 1 in 10 000 white blood cell events. Follow-up is for 12 months.

MRD testing will require a bone marrow biopsy sample. The bone marrow biopsy and MRD testing is a procedure performed routinely, irrespective of clinical trial participation. MRD testing by flow cytometry will be performed in accordance with standard procedures by the treating hospital and additionally by the Peter MacCallum Cancer Centre for the sole purpose of assessing inter-observer variability. Only the results performed by the treating hospital will be made available to the treating physician/patient in accordance with standard of care.
Intervention code [1] 296398 0
Not applicable
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 300189 0
To compare, in a prospective setting, the time to morphological relapse (TTMR) between patients who are MRD+ at a specific time point, and those who are MRD- at that time point.

MRD will be performed by flow cytometric methods on a sample of bone marrow. The TTMR will be assessed by review of medical records. Morphological remission will be determined in accordance with standard of care by the treating hospital.
Timepoint [1] 300189 0
1, 3 and 6 months post allograft.
Secondary outcome [1] 329277 0
Amongst patients who are MRD+ at all time points (pre-allograft and 1, 3, and 6 months post-allograft), to test for the existence of an association between time to deciding upon pre-emptive treatment and each of TTMR and OS.

MRD will be assessed by flow cytometry. TTMR and OS will be determined by review of medical records.
Timepoint [1] 329277 0
1, 3 and 6 months post allograft
Secondary outcome [2] 329480 0
Amongst patients who were MRD+ pre-allograft, for each of the post-allograft MRD test time points (1, 3 and 6 months) to test for a difference in TTMR and OS between those who remained MRD+ at the MRD test time point, and those who converted to MRD- by the MRD test time point.
MRD will be assessed by flow cytometry. TTMR and OS will be determined by review of medical records.
Timepoint [2] 329480 0
1, 3 and 6 months post allograft
Secondary outcome [3] 329481 0
To assess TTMR and OS between patients who were MRD- pre-allograft and remained MRD- at all post-allograft test time points (1, 3 and 6 months post allograft) and patients who were MRD+ pre-allograft and remained MRD+ at post-allograft all test time points.
MRD will be assessed by flow cytometry. TTMR and OS will be determined by review of medical records.
Timepoint [3] 329481 0
1, 3 and 6 months post allograft
Secondary outcome [4] 329482 0
To determine the explanatory power of combined WT1 expression in bone marrow (BM) in addition to MRD status at 1, 3 and 6 months post-allograft, as a predictor of TTMR. This is an exploratory outcome.

WT1 expression will be assessed by next-generation sequencing.
Timepoint [4] 329482 0
1, 3 and 6 months post allograft
Secondary outcome [5] 329483 0
To describe the mutational characteristics by targeted massive parallel sequencing at the pre-allograft time-point and 3 and 6 months post-allograft and test for association between identified mutations of interest and each of time to flow-relapse (TTFR), TTMR and OS. This is an exploratory outcome.

TTMR and OS will be determined by review of medical records.
Timepoint [5] 329483 0
3 and 6 months post allograft
Secondary outcome [6] 329484 0
To describe potential new molecular MRD markers. This is an exploratory outcome and will be assessed on the bone marrow sample.

Molecular markers will be determined by next-generation sequencing.
Timepoint [6] 329484 0
1, 3 and 6 months post allograft
Secondary outcome [7] 329485 0
To determine the degree of inter-reporter agreement between the 3 institutions performing flow cytometric MRD analysis.


Timepoint [7] 329485 0
1,3 and 6 months post allograft.

Eligibility
Key inclusion criteria
Patients over 18years who are scheduled for an allograft for acute myeloid leukaemia.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Persistent morphological disease

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
It is planned to enter 120 patients (20 patients per centre per year, with 3 centres - Victorian Comprehensive Cancer Centre,, the Alfred Hospital and Westmead Hospital) in this trial. Accrual is expected to be completed in 24 months. This initial accrual number predicts 100 pts available for 12 month follow-up. The predicted accrual number is based on the number of transplants performed for each centre in previous years. The following power calculation, based on the primary objective, assumes the following parameter values for the trial.
* a 2 year survival rate of 75% in the MRD- (i.e. 4.8 year median survival)
* a 2 year survival rate of 45 % in the MRD+ (i.e. 1.7 year median survival)
(which corresponds to a hazard ratio of 2.78 )
* an available sample size of 100
* a 60:40 (MRD- vs. MRD+) ratio
* a 2 year accrual period
* a 1 year follow-up period after accrual of the last patient
* a 2-sided type I error rate of 0.05
Then assuming a constant hazard within each group the resulting power is 0.86.

Univariate Cox proportional hazards regression models will be built to determine the time to morphological relapse and overall survival.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/12/2016
Actual
Date of last participant enrolment
Anticipated
1/12/2018
Actual
Date of last data collection
Anticipated
1/12/2019
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 6930 0
Westmead Hospital - Westmead
Recruitment hospital [2] 6931 0
The Alfred - Prahran
Recruitment hospital [3] 6932 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [4] 6933 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 14608 0
2145 - Westmead
Recruitment postcode(s) [2] 14609 0
3004 - Prahran
Recruitment postcode(s) [3] 14610 0
3000 - Melbourne
Recruitment postcode(s) [4] 14611 0
3050 - Parkville

Funding & Sponsors
Funding source category [1] 294967 0
Hospital
Name [1] 294967 0
Peter MAcCallum Cancer Centre
Country [1] 294967 0
Australia
Primary sponsor type
Hospital
Name
Peter MacCallum Cancer Centre
Address
305 Grattan St, Melbourne, VIC 3000
Country
Australia
Secondary sponsor category [1] 293787 0
None
Name [1] 293787 0
Address [1] 293787 0
Country [1] 293787 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296326 0
Peter MacCallum Cancer Centre Ethics Committee
Ethics committee address [1] 296326 0
Ethics committee country [1] 296326 0
Australia
Date submitted for ethics approval [1] 296326 0
27/08/2015
Approval date [1] 296326 0
01/02/2016
Ethics approval number [1] 296326 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 70462 0
Dr Denise Lee
Address 70462 0
Peter MaCallum Cancer Centre
Level 4 Pathology
305 Grattan St
Melbourne
VIC 3000
Country 70462 0
Australia
Phone 70462 0
+61450305524
Fax 70462 0
Email 70462 0
[email protected]
Contact person for public queries
Name 70463 0
Denise Lee
Address 70463 0
Peter MaCallum Cancer Centre
Level 4 Pathology
305 Grattan St
Melbourne
VIC 3000
Country 70463 0
Australia
Phone 70463 0
+61450305524
Fax 70463 0
Email 70463 0
[email protected]
Contact person for scientific queries
Name 70464 0
Denise Lee
Address 70464 0
Peter MaCallum Cancer Centre
Level 4 Pathology
305 Grattan St
Melbourne
VIC 3000
Country 70464 0
Australia
Phone 70464 0
+61450305524
Fax 70464 0
Email 70464 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
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