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Trial registered on ANZCTR


Registration number
ACTRN12621000246886p
Ethics application status
Submitted, not yet approved
Date submitted
19/10/2020
Date registered
8/03/2021
Date last updated
8/03/2021
Date data sharing statement initially provided
8/03/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
AMLM22/D3 - The International Acute myeloid leukaemia (AML) Platform Consortium (IAPC) trial is a randomised, multi-arm study platform to compare the efficacy of experimental therapies versus standard of care in patients with acute myeloid leukaemia in first complete remission.
Scientific title
AMLM22/D3-The International Acute myeloid leukaemia (AML) Platform Consortium (IAPC) trial is a randomised, multi-arm study platform to compare the efficacy of experimental therapies versus standard of care in subjects with acute myeloid leukaemia in first complete remission. Domain 3 is investigating the safety and efficacy of an Astrazeneca drug labelled AZD5153 as a maintenance therapy option.
Secondary ID [1] 302550 0
NIL
Universal Trial Number (UTN)
Trial acronym
AMLM22/D3
Linked study record
This study is linked to the below studies as they are all domains of the study.
ACTRN12619000248167p
ACTRN12619000280101

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukaemia (AML) 319424 0
Condition category
Condition code
Cancer 317396 317396 0 0
Leukaemia - Acute leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Domain 3 is AMLM22/D3, will determine the safety and efficacy of AZD5153 and it will be conducted in two stages:
Stage 1: A safety run-in stage will confirm the planned optimal dose schedule. At least 9 and up to 18 patients will be enrolled in cohorts of 3 patients.

If initial dose level of AZD5153 is deemed intolerable, other dose levels will be explored. Decisions to escalate or de-escalate the dose and the identification of the optimal dose will be guided by use of a Bayesian Optimal Interval (BOIN) design.

Stage 2: Once the safety run-in phase is satisfactorily completed, patients will be randomised to either treatment arm 1:AZD5153 (casules; taken orally)at the identified optimal dose or treatment arm 2:standard of care (clinical observation) will commence.

Each treatment cycle will be 21days or 28days

Dose level +2
40 mg daily for 14 days of 21 day cycle or
40 mg daily for 14 days of 28 day cycle

Dose level +1
30 mg daily for 14 days of 21 day cycle or
30 mg daily for 14 days of 28 day cycle

Starting dose
20 mg daily for 14 days of 21 day cycle or
20 mg daily for 14 days of 28 day cycle

Dose level -1
15 mg daily for 14 days of 21 day cycle or
15 mg daily for 14 days of 28 day cycle

Dose level -2
10 mg daily for 14 days of 21 day cycle or
10 mg daily for 14 days of 28 day cycle

Dose level -3
5 mg twice daily for 14 days of 21 day cycle or
5 mg twice daily for 14 days of 28 day cycle
Intervention code [1] 318841 0
Treatment: Drugs
Comparator / control treatment
Patients that are randomised to treatment arm 2: standard of care, will receive standard of care treatment for AML remission, which is currently clinical observation. This is the care they would normally receive if they weren't on a trial.
Control group
Active

Outcomes
Primary outcome [1] 325432 0
Failure-free survival - this is the time from randomisation until the time of the earliest leukaemia event (relapse). Data to monitor failure-free survival (disease monitoring and MRD testing) will be collected from patient's at various protocol specified times points throughout the study.
Timepoint [1] 325432 0
Time from randomisation until the time of the earliest leukemia event- either MRD progression, MRD relapse, clinical relapse or death.
Secondary outcome [1] 387929 0
Safety (pilot phase)- Occurrence of related CTCAE grade 3-5 non-hematologic adverse events, related CTCAE grade 4-5 neutropenia or thrombocytopenia or grade 3-5 febrile neutropenia.
Timepoint [1] 387929 0
Analysis of these adverse events will be conducted on all patients in the safety set (defined as all patients in an experimental arm that received at least one dose of the study drug associated with that arm and all patients in the appropriate SoC control arm who did not receive a dose of a drug associated with a study arm in the relevant domain), in the first 6 months following randomisation.
Summary tables of newly emerging and worsening adverse events and laboratory tests (based on the worst CTCAE grade per patient), both severe (greater than or equal to Grade 3) and of any grade, will be reported by type, treatment arm and by cycles (for each of the first 6 cycles).
Secondary outcome [2] 387930 0
Overall survival
Timepoint [2] 387930 0
Overall survival from the date of randomisation until date of last contact including a sensitivity analysis on overall survival with additional censoring at the earlier of the date of additional or alternative therapy (including SCT).
Secondary outcome [3] 387931 0
Relapse free survival- Time from the date of randomisation to the date of relapse or death from any cause.
Relapse data will be collected from the patient and the patients hospital records.
Timepoint [3] 387931 0
Time from the date of randomisation to the earlier of the date of relapse or death from any cause, (censored and not censored for SCT).
Secondary outcome [4] 387932 0
Measurable Residual Disease (MRD) erasure -Eradication of MRD that was detected at screening in bone marrow or peripheral blood within 6 months of study randomisation. This will be assessed using flow cytometry and/or molecular methods (ie.quantitative PCR)
Timepoint [4] 387932 0
Eradication of MRD detected at screening within 6 months of study randomisation
Secondary outcome [5] 387933 0
Quality of life
Timepoint [5] 387933 0
The FACIT-Fatigue Scale and the EQ-5D score at baseline, 6, 12, 18 and 24 months

Eligibility
Key inclusion criteria
1. Provision of written informed consent
2. Provision of written informed consent to the ALLG NBCR
3. Age 18+ (Age 16-17 permitted if consent for minor PICF approved by the authorizing HREC)
4. AML (excluding APL) in first complete remission with bone marrow blasts <5%
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Chemotherapy or investigational agents within 28 days of planned study cycle 1 day 1
2. History of other malignancy requiring active systemic treatment or which is likely to result in an expected survival time of less than 2 years
3. Viral infection with known HIV or viral hepatitis type B or C not adequately controlled by antiviral medication
4. Prior bone marrow or stem cell transplantation

AMLM22/D3 specific exclusion criteria:
1. Presence of any general exclusion criteria outlined in in IAPC master protocol.
2. Platelet count greater than or equal to 100 x 10^9 /L
3. Increased bleeding risk as a result of:
a. Use of parenteral anticoagulants at therapeutic levels, warfarin or direct oral anticoagulants within 14 days prior to the first dose of AZD5153.
b. Coagulation parameters (prothrombin time/international normalised ratio [PT/INR] and activated partial thromboplastin time [APTT]) less than or equal to 1.5 x upper limit of normal (ULN)
4. Cardiac abnormalities as evidenced by any of the following:
a. Clinically significant conduction abnormalities or uncontrolled arrhythmia.
b. Uncontrolled hypertension
c. Greater than or equal to New York Heart Association (NYHA) class II congestive cardiac failure and/or left ventricular ejection fraction < 50% by echocardiogram (ECHO) or multi gated acquisition scan (MUGA)
d. ECG findings demonstrating baseline a QTcF interval greater than or equal to 450 ms
5. Subject not able to comply with domain-specific contraception recommendations below:
a. Female patients must use two highly effective contraceptive measures. All methods of contraception (with the exception of total abstinence) should be used in combination with the use of a condom by a male sexual partner for intercourse.
b. Female patients must not be breast-feeding and must have a negative pregnancy test prior to start of dosing if of childbearing potential or must have evidence of non-childbearing potential by fulfilling one of the following criteria at screening:
i. Post-menopausal women defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatment.
ii. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, but not tubal ligation.

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)
Randomisation will occur by a central randomization procedure, in a 2-step process.
Participants will first be randomised to an eligible domain based on physical and disease characteristics. They will then be randomised to a treatment arm within that domain.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
30/04/2021
Actual
Date of last participant enrolment
Anticipated
30/04/2024
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] 306986 0
Charities/Societies/Foundations
Name [1] 306986 0
Australian Leukaemia and Lymphoma Group (ALLG)
Country [1] 306986 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Australian Leukaemia and Lymphoma Group (ALLG)
Address
35 Elizabeth Street
Richmond, VIC 3121
Country
Australia
Secondary sponsor category [1] 307551 0
Commercial sector/Industry
Name [1] 307551 0
Astrazeneca
Address [1] 307551 0
(AstraZeneca Pty Ltd, a company incorporated in Australia, whose registered office is at 66 Talavera Rd, Macquarie Park, NSW 2113
Country [1] 307551 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 307119 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 307119 0
Ethics committee country [1] 307119 0
Australia
Date submitted for ethics approval [1] 307119 0
11/02/2021
Approval date [1] 307119 0
Ethics approval number [1] 307119 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 106094 0
Dr Chun Yew Fong
Address 106094 0
Austin Health
Level 4, ONJ Centre
145 Studley Road, Heidelberg
PO Box 5555, Victoria, 3084
Country 106094 0
Australia
Phone 106094 0
+61 3 9496 5000
Fax 106094 0
Email 106094 0
chun.FONG@austin.org.au
Contact person for public queries
Name 106095 0
Chun Yew Fong
Address 106095 0
Austin Health
Level 4, ONJ Centre
145 Studley Road, Heidelberg
PO Box 5555, Victoria, 3084
Country 106095 0
Australia
Phone 106095 0
+61 3 9496 5000
Fax 106095 0
Email 106095 0
chun.FONG@austin.org.au
Contact person for scientific queries
Name 106096 0
Chun Yew Fong
Address 106096 0
Austin Health
Level 4, ONJ Centre
145 Studley Road, Heidelberg
PO Box 5555, Victoria, 3084
Country 106096 0
Australia
Phone 106096 0
+61 3 9496 5000
Fax 106096 0
Email 106096 0
chun.FONG@austin.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 publically. 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.