ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

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To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

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

3/08/2024

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]

ALLG - AMLM28 (ADAPT)

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Acute Myeloid Leukaemia

Condition category

Condition code

Cancer

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]

Treatment: Drugs

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

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]

End of cycles 1, 2, 4, 8 and at the end of 12 months post-enrolment.

Secondary outcome [1]

Nil

Timepoint [1]

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?

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

31/08/2024

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)

ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors

Funding source category [1]

Other Collaborative groups

Name [1]

Australasian Leukaemia and Lymphoma Group (ALLG)

Address [1]

ALLG Ground floor, 35 Elizabeth St Richmond VIC 3121

Country [1]

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]

None

Name [1]

None

Address [1]

None

Country [1]

Ethics approval

Ethics application status

Not yet submitted

Ethics committee name [1]

Peter MacCallum Cancer Centre Ethics Committee

Ethics committee address [1]

305 Grattan Street, Melbourne VIC 3000

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

25/09/2023

Approval date [1]

Ethics approval number [1]

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

A/Prof Andrew Wei

Address

Peter MacCallum Cancer Centre
305 Grattan Street
Melbourne VIC 3000

Country

Australia

Phone

+61 3 8559 5000

Fax

andrew.wei@petermac.org

Contact person for public queries

Name

Delaine Smith

Address

Australasian Leukaemia and Lymphoma Group Ground Floor, 35 Elizabeth Street, Richmond VIC 3121

Country

Australia

Phone

+61 3 8373 9701

Fax

delaine.smith@allg.org.au

Contact person for scientific queries

Name

Delaine Smith

Address

Australasian Leukaemia and Lymphoma Group Ground Floor, 35 Elizabeth Street, Richmond VIC 3121

Country

Australia

Phone

+61 3 8373 9701

Fax

delaine.smith@allg.org.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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.

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