AMLM28 (ADAPT)
AMLM28 Platform Trial – Achieving Durable remissions via Adaptive Pro-survival Targeting in Acute Myeloid Leukaemia (AML) (ADAPT)
Leukaemia – Acute leukaemia
This platform trial will initially enrol patients to the ALLG National Blood Cancer AML Registry (NBCR) which acts as an umbrella screening framework for AML trials conducted by the ALLG. Patients unfit for intensive chemotherapy will receive VEN-AZA. The NBCR will allow clinical data collection, storage of baseline samples for future research and MRD determination as part of standard of care. If at any stage the patient becomes eligible for participation in the AMLM28 ADAPT study, the patient will be invited to sign the applicable AMLM28 ADAPT consent form to enable trial registration and screen for one of the interventional therapy domains.
Who is it for?
You may be eligible for this study if you are aged 18 and above and have been diagnosed with AML, elderly and un-fit for intensive chemotherapy.
A summary of proposed AMLM28 ADAPT domains are detailed below
ADAPT-STOP Domain
• Patients enrolled to the NBCR, receiving VEN-AZA and achieving CR/CRi/CRh MRD negative status and still negative 10-14 months after commencing VEN-AZA will be eligible to consent to “ADAPT-STOP” Domain. Patients must have completed at least 8 cycles of VEN-AZA before ceasing therapy in this domain
Alternatively, patients may also be considered for eligibility to the ALLG AMLM26 INTERCEPT study (Registration number: ACTRN12621000439842p).
ADAPT TP53 domain
If a patient enrolled to the NBCR and receiving VEN-AZA, is found to have one or more TP53 aberrations (defined as TP53 mutation (at any variant allele frequency (VAF)), del17p or monosomy 17), the patient will be eligible to consent to “ADAPT TP53” Domain. This should occur after the first cycle of VEN-AZA. If a patient is TP53 and FLT3-ITD positive, this patient will be assigned to the TP53 domain.
ADAPT FLT3 domain
Patients enrolled to the NBCR, receiving VEN-AZA is found to have a FLT3 mutation, the patient will be eligible to consent to “ADAPT FLT3” Domain. This should occur prior to day 7 of VEN-AZA.
ADAPT MRD domain
If a patient enrolled to the NBCR, receiving VEN-AZA, after cycle 4, is found to have les than 10% blasts with positive MRD. E.g. equal to 0.1% aberrant cells by flow cytometry, the patient will be eligible to consent to “ADAPT MRD” domain. Cycle 4 will need to have been completed within 8-months from Cycle 1 Day 1.
Patients can be co-enrolled to INTERCEPT monitoring phase and not INTERCEPT treatment phase. If patient has MRD relapse and goes on INTERCEPT treatment, AMLM28 will follow them up for survival via the NBCR Registry database.
It is hoped this research will deliver adaptive interventions to improve clinical outcomes in patients receiving frontline VEN-AZA for newly diagnosed AML.
Key inclusion criteria
• Confirmed diagnosis of AML* (ambiguous lineage with myeloid overlap is permitted) as per WHO or ICC 2022 criteria. *MDS/AML per ICC 2022 criteria permitted if patient is planned for AZA-VEN therapy
• Registration on the ALLG National Blood Cancer Registry (NBCR)
• Age equal to or greater than 18 years
• Patient has received or planned to receive Venetoclax and Azacitidine
• Registration on the ALLG National Blood Cancer Registry (NBCR)
• Age equal to or greater than 18 years
• Patient has received or planned to receive Venetoclax and Azacitidine
Minimum age: 18 Years
Maximum age: No limit
Sex: Both males and females
Healthy volunteers: No
Key exclusion criteria
Acute promyelocytic leukaemia
Known active Central Nervous System (CNS) disease
Relapsed AMLThere will be additional arm specific eligibility criteria which will be specified in the domain-specific protocols
Known active Central Nervous System (CNS) disease
Relapsed AMLThere will be additional arm specific eligibility criteria which will be specified in the domain-specific protocols
Dr. Carolyn Grove
Australasian Leukaemia & Lymphoma Group
Phase 2
ALLG – AMLM28 (ADAPT)
ACTRN12623000900617