Please note the ANZCTR will be unattended from Friday 20 December 2019 for the holidays. The Registry will re-open on Tuesday 07 January 2020. Submissions and updates will not be processed during that time.

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Trial registered on ANZCTR


Registration number
ACTRN12619000248167
Ethics application status
Approved
Date submitted
12/02/2019
Date registered
19/02/2019
Date last updated
8/10/2019
Date data sharing statement initially provided
19/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
AMLM22/D1: 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/D1: 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.
Secondary ID [1] 297410 0
NIL
Universal Trial Number (UTN)
Trial acronym
AMLM22/D1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute myeloid leukaemia (AML) 311494 0
Condition category
Condition code
Cancer 310128 310128 0 0
Leukaemia - Acute leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Domain 1 is AMLM22/D1, it has 2 treatment arms:
Arm 1: Molibresib (investigational product). Recommended dose of Molibresib is 60mg daily, taken orally 28 days per cycle. Each cycle is 28 days. Total treatment duration is expected to be 24 months.
Arm 2: standard of care (generally observation)
Patients will be asked to return any unused molibresib tablets at each visit, for drug accountability
Intervention code [1] 313613 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 generally observation. This is the care they would normally receive if they weren't on a trial.
Control group
Active

Outcomes
Primary outcome [1] 319035 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] 319035 0
Time from randomisation until the time of the earliest leukemia event- either MRD progression, MRD relapse, clinical relapse or death.
Secondary outcome [1] 366765 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] 366765 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] 366766 0
Overall survival
Timepoint [2] 366766 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] 366767 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] 366767 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] 366768 0
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] 366768 0
Eradication of MRD detected at screening within 6 months of study randomisation
Secondary outcome [5] 366769 0
Quality of life
Timepoint [5] 366769 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%

There is no AMLM22/D1 specific inclusion criteria. Inclusion to this domain is what is outlined above
Minimum age
16 Years
Maximum age
No limit
Gender
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
2. Impaired hematologic recovery 8 weeks after last chemotherapy
a. Grade 2 anemia (Hb <100g/L)
b. Grade 4 neutropenia (N <0.5 x 109/L)
c. Grade 3 thrombocyotopenia (Plt <50 x 109/L)
3. History of other malignancy requiring active systemic treatment or which is likely to result in an expected survival time of < 2 years
4. Viral infection with known HIV or viral hepatitis type B or C not adequately controlled by antiviral medication
5. Prior bone marrow or stem cell transplantation

AMLM22/D1 specific exclusion criteria:
1. Presence of any general exclusion criteria outlined in in IAPC master protocol.
2. Prior solid organ transplant.
3. Cardiac abnormalities as evidenced by any of the following:
a. Clinically significant conduction abnormalities or uncontrolled arrhythmia.
b. Greater than or equal to New York Heart Association (NYHA) class II congestive cardiac failure and/or ejection fraction < 50% by echocardiogram (ECHO) or multi gated acquisition scan (MUGA)
c. Unstable angina or myocardial infarction with coronary angioplasty/stenting within the last 3 months
d. ECG findings demonstrating baseline a QTcF interval greater than or equal to 480 ms
4. Increased bleeding risk as a result of:
a. Use of anticoagulants at therapeutic levels within 7 days prior to the first dose of Molibresib (GSK525762).
b. Evidence of active bleeding or major bleed within the last 3 months.
c. Coagulation parameters (prothrombin time/international normalised ratio [PT/INR] and activated partial thromboplastin time [APTT]) greater than or equal to 1.2 x upper limit of normal (ULN)
5. Subject not able to comply with domain-specific contraception recommendations

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
Recruiting
Date of first participant enrolment
Anticipated
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] 301940 0
Charities/Societies/Foundations
Name [1] 301940 0
Australian Leukaemia and Lymphoma Group (ALLG)
Address [1] 301940 0
35 Elizabeth Street
Richmond, VIC 3121
Country [1] 301940 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] 301694 0
Commercial sector/Industry
Name [1] 301694 0
GlaxoSmithKline (GSK)
Address [1] 301694 0
980 Great West Road,
Brentford, Middlesex, TW8 9GS,
Country [1] 301694 0
United Kingdom

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302622 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 302622 0
35 Commercial Road
Melbourne, VIC 3004
Ethics committee country [1] 302622 0
Australia
Date submitted for ethics approval [1] 302622 0
09/01/2019
Approval date [1] 302622 0
19/06/2019
Ethics approval number [1] 302622 0
HREC/48451/Alfred-2018

Summary
Brief summary
This study will evaluate the safety and efficacy of Molibresib for Acute Myeloid Leukemia

Who is it for?
You may be eligible to join this study if you are aged 16 and above and have Acute Myeloid Leukemia in first complete remission.

Study details
This study is part of the International AML Platform Consortium. Participants in this study will be randomly allocated (by chance) to one of two groups. Participants in one group will receive standard care which generally observation. Participants in the other group will receive the drug Molibresib daily for a total of 24 months.

As part of the study, participants will have blood tests at the start of each cycle (every 28 days) as well as an ECG to monitor heart function.
Molibresib is known to have adverse effects on the heart therefore, participants will also have a MUGA (MUltiple Gated Acquisition scan) or ECHO (echocardiogram) at screening, cycle 2 and then every 12 weeks thereafter.
We hope that the results from this trial will be used to help these new treatments which may be better for people with AML than what is currently available ,become accessible to the general population at faster than the normal process.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31526 0
A/Prof Andrew Wei
Address 31526 0
The Alfred Hospital
55 Commercial Rd
Melbourne, VIC 3004
Country 31526 0
Australia
Phone 31526 0
+61 3 9076 3392
Fax 31526 0
Email 31526 0
andrew.wei@monash.edu
Contact person for public queries
Name 14773 0
A/Prof Andrew Wei
Address 14773 0
The Alfred Hospital
55 Commercial Rd
Melbourne, VIC 3004
Country 14773 0
Australia
Phone 14773 0
+61 3 9076 3392
Fax 14773 0
Email 14773 0
andrew.wei@monash.edu
Contact person for scientific queries
Name 5701 0
A/Prof Andrew Wei
Address 5701 0
The Alfred Hospital
55 Commercial Rd
Melbourne, VIC 3004
Country 5701 0
Australia
Phone 5701 0
+61 3 9076 3392
Fax 5701 0
Email 5701 0
andrew.wei@monash.edu

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 other documents available
Summary results
No Results