Trial Review

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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12623000900617p
Ethics application status
Not yet submitted
Date submitted
15/03/2023
Date registered
22/08/2023
Date last updated
22/08/2023
Date data sharing statement initially provided
22/08/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
AMLM28 Platform Trial - Achieving Durable remissions via Adaptive Pro-survival Targeting in Acute Myeloid Leukaemia (AML) (ADAPT)
Scientific title
AMLM28 Platform Study (Master Protocol) - Achieving Durable remissions via Adaptive Pro-survival Targeting in Acute Myeloid Leukaemia (AML) patients receiving Venetoclax and Azacitidine (VEN-AZA) as frontline therapy
Secondary ID [1] 309171 0
ALLG - AMLM28 (ADAPT)
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukaemia 329300 0
Condition category
Condition code
Cancer 326245 326245 0 0
Leukaemia - Acute leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients will be enrolled into Master Protocol and commence on Venetoclax and Azacitidine (VEN-AZA).
Venetoclax - taken as an oral tablet following the schedule below:
- 100mg on day 1
- 200mg on day 2
- 400mg on day 3
- 50mg from day 4 - 21
Azacitidine will be administered either intravenously or subcutaneously at 75mg/m^2 daily on days 1-7.

Subsequent adaptive interventions will be based on the patient’s response to treatment after starting VEN-AZA. There are currently two domains anticipated for the AMLM28 platform trial.

Domain 1 consists of two different strata:
- TP53 stratum - Patients who are found to have TP53 aberrations during or after cycle 1 may be eligible
- Measurable Residual Disease (MRD) persistence stratum - Patients found to have less than 10percent blasts with positive MRD greater than or equal to 0.1 percent after cycle 4 may be eligible
- Treatment for all patients in domain 1 will be with VEN-AZA + Navitoclax and is detailed in the domain-specific ANZCTR submission.

Domain 2 (ADAPT-STOP) - This platform study will have a prospective arm to investigate potential to cease therapy in patients who have received VEN-AZA and in continuous CR and MRD negative for over 12 months. This domain may be available for patients that achieve complete response with MRD negativity at 12 months of VEN-AZA. Patients can opt in or out of this domain . Those that opt-in will be randomised to stop VEN-AZA treatment at either 12-13 months or after 18 months. Patients who opt-out of ADAPT-STOP and continue on VEN-AZA will remain on the master protocol and undergo monitoring.

As a platform trial, the master protocol will allow the addition of new treatment options through new trial domains, thus serving as a flexible and effective vehicle to optimise treatment outcomes for patients receiving VEN-AZA.

Patients suitable for an intervention to an ADAPT domain must fulfill the eligibility criteria for the specific intervention. There will not be movement of patients from one domain to another .
Futility/failure of a treatment arm will be considered by the trial management committee and the ALLG safety and data monitoring committee in the event of any of the following:
1. Inadequate recruitment
2. Unacceptable toxicity
3. Evidence becoming available during the accrual phase of the trial, which clearly demonstrates that it is unethical to allocate patients to trial arms within a stratum.

MRD progression will be assessed at the end of cycles 1, 2, 4, 8 and 12, after 12 months of VEN-AZA, and every 4 months onwards (for another 12 months).

All treatment will be administered by the study team. Drug accountability will be performed by the administering institutions to assess compliance.
Intervention code [1] 325617 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 334117 0
To develop a centralised network to Monitor Measurable Residual Disease (MRD) progression in patients receiving VEN-AZA assessed by flow cytometry and molecular assessment.
Timepoint [1] 334117 0
End of cycles 1, 2, 4, 8 and at the end of 12 months post-enrolment.
Secondary outcome [1] 419416 0
Nil
Timepoint [1] 419416 0
Nil

Eligibility
Key inclusion criteria
-Provision of informed consent
-Newly diagnosed acute myeloid leukaemia (ambiguous lineage with myeloid overlap is permitted)
-Registration on the ALLG National Blood Cancer Registry (NBCR)
-Age of at least 18 years
-Eligible for Venetoclax and Azacitidine

There will be additional arm specific eligibility criteria which will be specified in the domain-specific protocols
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Acute promyelocytic leukaemia
Known active Central Nervous System (CNS) disease
Relapsed AML

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



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
20/11/2023
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 313369 0
Other Collaborative groups
Name [1] 313369 0
Australasian Leukaemia and Lymphoma Group (ALLG)
Country [1] 313369 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Leukaemia and Lymphoma Group (ALLG)
Address
ALLG Ground floor, 35 Elizabeth St Richmond VIC 3121
Country
Australia
Secondary sponsor category [1] 315129 0
None
Name [1] 315129 0
None
Address [1] 315129 0
None
Country [1] 315129 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 312587 0
Peter MacCallum Cancer Centre Ethics Committee
Ethics committee address [1] 312587 0
305 Grattan Street, Melbourne VIC 3000
Ethics committee country [1] 312587 0
Australia
Date submitted for ethics approval [1] 312587 0
25/09/2023
Approval date [1] 312587 0
Ethics approval number [1] 312587 0

Summary
Brief summary
This platform trial will initially enroll patients to the Australasian Leukaemia and Lymphoma Group (ALLG) National Blood Cancer Registry (NBCR) which acts as the initial gateway to data collection and Acute Myeloid Leukaemia (AML) trials for the ALLG. Patients unfit for intensive chemotherapy and planned to receive Venetoclax and Azacitidine (VEN-AZA) as standard of care will be invited to sign the AMLM28 ADAPT master consent form. This trial will utilise serial Minimal Residual Disease (MRD) monitoring, performed centrally, to guide adaptive changes in therapy aimed at improving patient outcomes and quality of life.
This platform trial aims to provide an overarching research framework that will enable research questions to be addressed prospectively and systematically for AML patients receiving VEN-AZA.

Who is it for?
You may be eligible for this study if you are aged 18 and above and have been diagnosed with AML.

Study details
Participants who choose to participate in this trial are required to consent to both the NBCR and the AMLM28 ADAPT platform prior to commencement of VEN-AZA. This is to enable a baseline and monitoring centralised MRD assessment to be performed.
Patients will be enrolled into the master protocol and commence on VEN-AZA. Subsequent adaptive interventions will be based on the patient’s response to treatment after starting VEN-AZA.

Domain 1 (ADAPT-Rx) consists of two different strata:
- TP53 stratum - Patients who are found to have TP53 aberrations during or after cycle 1 may be eligible
- Measurable Residual Disease (MRD) persistence stratum - Patients found to have less than 10percent blasts with positive MRD greater than or equal to 0.1 percent after cycle 4 may be eligible

Domain 2 (ADAPT-STOP) – will investigate whether it is safe to stop therapy in patients responding well to VEN-AZA therapy.

Patients who do not meet eligibility criteria to enter the above Domains (e.g., refractory disease without TP53 aberrations) may continue to receive VEN-AZA therapy or come off study as per investigator discretion.
If the patient experiences MRD relapse or morphologic relapse at any stage of the study, the patient may be considered for eligibility for the ALLG AMLM26 INTERCEPT study.

It is hoped this research will deliver adaptive interventions to improve clinical outcomes in patients receiving frontline VEN-AZA for newly diagnosed AML.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 125194 0
A/Prof Andrew Wei
Address 125194 0
Peter MacCallum Cancer Centre
305 Grattan Street
Melbourne VIC 3000
Country 125194 0
Australia
Phone 125194 0
+61 3 8559 5000
Fax 125194 0
Email 125194 0
andrew.wei@petermac.org
Contact person for public queries
Name 125195 0
Ms Delaine Smith
Address 125195 0
Australasian Leukaemia and Lymphoma Group Ground Floor, 35 Elizabeth Street, Richmond VIC 3121
Country 125195 0
Australia
Phone 125195 0
+61 3 8373 9701
Fax 125195 0
Email 125195 0
delaine.smith@allg.org.au
Contact person for scientific queries
Name 125196 0
Ms Delaine Smith
Address 125196 0
Australasian Leukaemia and Lymphoma Group Ground Floor, 35 Elizabeth Street, Richmond VIC 3121
Country 125196 0
Australia
Phone 125196 0
+61 3 8373 9701
Fax 125196 0
Email 125196 0
delaine.smith@allg.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual patient data will not be shared publicly. Aggregate patient data and final results will be presented in the final report.


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.