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Trial registered on ANZCTR


Registration number
ACTRN12624000065594p
Ethics application status
Not yet submitted
Date submitted
28/11/2023
Date registered
25/01/2024
Date last updated
25/01/2024
Date data sharing statement initially provided
25/01/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
ALLG AMLM28/STOP: Achieving Durable remissions via Adaptive Pro-survival Targeting in Acute Myeloid Leukaemia (AML) (ADAPT): The ADAPT Platform trial - STOP Domain
Scientific title
ALLG AMLM28/STOP: Achieving Durable remissions via Adaptive Pro-survival Targeting in Acute Myeloid Leukaemia (AML) (ADAPT): The ADAPT Platform trial - STOP Domain
Secondary ID [1] 311050 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukaemia 332169 0
Condition category
Condition code
Cancer 328887 328887 0 0
Leukaemia - Acute leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
AMLM28 ADAPT-STOP domain aims to address the question of whether it is safe to stop therapy in patients responding well to venetoclax and Azacitidine (VEN-AZA) therapy.

All patients in the ADAPT Master trial (ACTRN12623000900617) that achieve Complete Remission (CR), CR with incomplete haematologic recovery (CRi) or CR with partial haematologic recovery (CRh) with undetectable Measurable Residual Disease (MRD) by 12 months (plus or minus 14 days) (from Cycle 1 Day 1) will be eligible to enter the ADAPT-STOP domain. These patients and their site investigators will have a choice between continuing therapy or electively ceasing therapy.
-Patients who continue therapy will remain on the ADAPT Master protocol.
-Patients who chose to electively cease therapy will be eligible to enter the ADAPT-STOP domain and will be randomised in a 1:1 ratio to the following:
o Ceasing therapy at 12-14 months (immediate-stop)
o Ceasing therapy at 18-20 months (delayed-stop)
-Following therapy cessation, central MRD will be monitored 3-monthly in the first 12 months followed by 6 monthly for the next 12 months. Monitoring will involve attending an appointment with their oncologist for a bone marrow aspirate (BMA) collection for flow cytometry MRD analysis, as well as blood tests.
-Patients will be followed-up for 3 years on the ADAPT-STOP domain and at least up to 5 years (6 monthly sweeps for overall survival and disease status via participation in the ALLG’s National Blood Cancer Registry (NBCR)).
-Patients experiencing morphological or MRD relapse may be enrolled to the ALLG AMLM26 INTERCEPT (ACTRN12621000439842) study if eligible and study is available at any time during a monitoring visit post-cessation, from 3 months post-cessation.

All treatment will be administered or ceased (for patients enrolled in the STOP domain) by the study team. Drug accountability will be performed by the administering institutions to assess compliance.


Intervention code [1] 327498 0
Treatment: Other
Comparator / control treatment
Continued VEN-AZA therapy (AMLM28 Master Protocol)
Control group
Active

Outcomes
Primary outcome [1] 336700 0
Comparison of Relapse-free survival (RFS) in patient groups continuing VEN-AZA vs. groups early stopping of VEN-AZA.
Timepoint [1] 336700 0
At 6 months from the date of randomisation.
Primary outcome [2] 336701 0
To determine the percentage of patients alive and in sustained CR/CRi/CRh with MRD negativity (less than 0.1percent) after elective therapy cessation post at least 12 months of Venetoclax-Azacitidine (VEN-AZA) therapy.
Timepoint [2] 336701 0
At three pre-defined landmarks: 12, 24 and 36 months from the date of stopping (defined as date of last dose of venetoclax and/or azacitidine (whichever comes later)).
Secondary outcome [1] 429365 0
To determine the duration of time remaining in MRD negative remission without ongoing therapy after elective therapy cessation whilst in CR/CRi/CRh with MRD negativity after at least 12 months of VEN-AZA therapy.
Timepoint [1] 429365 0
Additional analysis adjusted for a landmark at 6 months from randomisation will be performed.
Secondary outcome [2] 429366 0
Overall survival (OS)
Timepoint [2] 429366 0
Overall survival measured from day 1 of VEN-AZA therapy to the date of death from any cause assessed continuously from enrolment until completion of trial (maximum 7 years).
Secondary outcome [3] 429367 0
Relapse free survival (RFS)
Timepoint [3] 429367 0
Assessed continuously from date of remission (CR/CRi/CRh on VEN-AZA therapy) until the completion of the trial.
Secondary outcome [4] 429368 0
Quality of life and fear of cancer recurrence assessments (assessed as a composite secondary outcome)
Timepoint [4] 429368 0
Every 3 months for the first 12 months, then 6 monthly for the next 12 months since entry into ADAPT-STOP.

Eligibility
Key inclusion criteria
ADAPT Master Protocol (ACTRN12623000900617):
-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

A patient will be eligible for study participation in this ADAPT STOP domain if the patient meets the following criteria:
1. Meets inclusion criteria outlined in the AMLM28 ADAPT Master Protocol (above)
2. Achieved a best response of CR, CRi or CRh
3. Undetectable MRD after 12 months (plus or minus 14 days) from starting VEN-AZA therapy.
a. Undetectable MRD is defined as either less than or equal to 0.1percent by flow cytometry and/or molecular MRD (for validated molecular markers [NPM1, RUNX1::RUNX1T1, CBFB::MYH11, KMT2Ar] with a limit of detection of at least 0.01%)
b. Two consecutive measurements of undetectable MRD performed at least 28 days apart will be required
4. Completed or due to complete greater than or equal to 8 cycles of VEN-AZA by end of 14 months from Cycle 1 day 1
5. Willingness and ability to comply with procedures required and follow-up required for the protocol
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
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software.
Masking / blinding
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
15/01/2025
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 315308 0
Other Collaborative groups
Name [1] 315308 0
Australasian Leukaemia and Lymphoma Group (ALLG)
Country [1] 315308 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Leukaemia and Lymphoma Group (ALLG)
Address
Ground Floor, 35 Elizabeth St, Richmond VIC 3121
Country
Australia
Secondary sponsor category [1] 317356 0
None
Name [1] 317356 0
Address [1] 317356 0
Country [1] 317356 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 314231 0
Peter MacCallum Cancer Centre Ethics Committee
Ethics committee address [1] 314231 0
305 Grattan Street, Melbourne VIC 3000
Ethics committee country [1] 314231 0
Australia
Date submitted for ethics approval [1] 314231 0
01/09/2024
Approval date [1] 314231 0
Ethics approval number [1] 314231 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 2 (ADAPT-STOP) aims to address the question of whether it is safe to stop therapy in patients responding well to venetoclax and azacitidine (VEN-AZA) therapy.

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 130874 0
A/Prof Andrew Wei
Address 130874 0
Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne VIC 3000
Country 130874 0
Australia
Phone 130874 0
+61 3 8559 5000
Fax 130874 0
Email 130874 0
andrew.wei@petermac.org
Contact person for public queries
Name 130875 0
Ms Delaine Smith
Address 130875 0
ALLG, 35 Elizabeth St, Richmond, VIC 3121
Country 130875 0
Australia
Phone 130875 0
+61 3 8373 9701
Fax 130875 0
Email 130875 0
delaine.smith@allg.org.au
Contact person for scientific queries
Name 130876 0
Ms Delaine Smith
Address 130876 0
ALLG, 35 Elizabeth St, Richmond, VIC 3121
Country 130876 0
Australia
Phone 130876 0
+61 3 8373 9701
Fax 130876 0
Email 130876 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.