None listed
Conditions
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. Approximately 50 “opt-in” patients will be initially randomised 1-to-1 to the treatment cessation arms. An interim analysis will be performed upon recruitment of 50 “opt-in” patients. A further expansion of recruitment up to 100 “opt-in” patients may be allowed, and will be determined by the Trial Management Committee and sponsor. Up to 50 “opt-out” patients will be followed for VEN-AZA treatment duration, PROs, disease status including relapse and survival. 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.
Interventions
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 t
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: "Opt-out Cohort" -Patients who chose to electively cease therapy "Opt-in Cohort" 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.
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.
Patients on standard of care VEN-AZA, who 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 of VEN-AZA) will be eligible to enter the ADAPT-STOP
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. Patients on standard of care VEN-AZA, who 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 of VEN-AZA) 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 standard of care VEN-AZA: "Opt-out Cohort" -Patients who choose to electively cease therapy "Opt-in Cohort" 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 and then at 36 months from ADAPT-STOP Registration. Monitoring will involve attending an appointment with their haematologist for a bone marrow aspirate (BMA) collection for flow cytometry and/or Molecular MRD analysis, as well as blood tests and quality of life questionnaires -Patients will be followed-up via the ALLG’s National Blood Cancer Registry (NBCR)). -Patients experiencing morphological or MRD relapse may be enrolled to the ALLG AMLM26 INTERCEPT (ACTRN12621000439842) 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.
Sponsors
Australasian Leukaemia and Lymphoma Group (ALLG)
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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
Exclusion criteria
- Acute promyelocytic leukaemia - Known active Central Nervous System (CNS) disease - Relapsed AML
Outcome results
None listed