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Trial registered on ANZCTR

Registration number
Ethics application status
Date submitted
Date registered
Date last updated
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Phase Ib/II Clinical Evaluation of the Safety of Combining the mTOR inhibitor Everolimus with 5-Azacitidine in Acute Myeloid Leukaemia (AML).
Scientific title
A Phase Ib/II Clinical Evaluation of the Safety of Combining the mTOR inhibitor Everolimus with 5-Azacitidine in AML
Secondary ID [1] 252942 0
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukaemia 258472 0
Condition category
Condition code
Cancer 258638 258638 0 0
Leukaemia - Acute leukaemia

Study type
Description of intervention(s) / exposure
Azacitidine injection given sub-cutaneously for 7 doses D1-5 and D8-9 of a 28 day cycle, dosages at 75mg/m2. Everolimus given orally d5-21, cohorts increasing 2.5mg, 5mg, 10mg. 28 day cycles continue unless disease progression, unacceptable toxicity, or stem cell transplant.
Intervention code [1] 257466 0
Treatment: Drugs
Comparator / control treatment
Control group

Primary outcome [1] 259481 0
To examine the safety and tolerability of Everolimus in combination with 5-azacitidine in AML, determined by Quality of Life assessments and Adverse Events. Examples of adverse events include gastrointestinal (nausea, vomiting and diarrhoea), haematological (anaemia, thrombocytopenia, leukopenia/neutropenia), and injection site reactions, also electrolyte imbalances. Adverse events will be assessed every day during D1-5 and D8-9 during treatment and twice weekly for the following 2 weeks of the cycle.
Timepoint [1] 259481 0
Continuously throughout cycle
Secondary outcome [1] 266064 0
To provide preliminary data that Everolimus in combination with 5-azacitidine may induce meaningful clinical responses and delay leukaemic relapse in patients with AML, determined by blood test and bone marrow biopsies.
Timepoint [1] 266064 0
Contiuously throughout cycle.
Secondary outcome [2] 266216 0
To assess biomarkers of response such as gene specific methylation and phosphorylayion status of mTOR targets, from laboratory studies.
Timepoint [2] 266216 0
Contiuously throughout cycle.
Secondary outcome [3] 266217 0
To assess patient related outcomes for patients receiving the Everolimus/5-azacitidine combination via adverse events and quality of life questionnaries.
Timepoint [3] 266217 0
Contiuously throughout cycle.

Key inclusion criteria
*Untreated AML patients (defined by WHO 2008 criteria) over the age of 60 or relapsed/refractory AML over the age of 18 who have received up to 2 previous lines of intensive chemotherapy
* No prior failure to achieve at least a PR with Azacitidine or Everolimus
* Provision of written informed consent
* Secondary AML (including therapy-related) are included
* Life expectancy of greater than 3 months in relation to diseases other then AML/MDS
* ECOG performance status 0 – 3
* Electrolyte levels (potassium, calcium (albumin-adjusted), magnesium, phosphorous) within normal limits (WNL) or easily correctable with supplements
* Adequate hepatic function as defined by bilirubin = 1.5 x the upper limit of normal (ULN) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 x ULN
* Adequate renal function, with serum creatinine = 1.5 x ULN or GFR > 30 ml/minute
* Patients with no uncontrolled active infection
* Hydroxyurea ceased 48 hours prior to study therapy
Minimum age
18 Years
Maximum age
No limit
Both males and females
Can healthy volunteers participate?
Key exclusion criteria
* Any serious medical or psychiatric conditions which the investigator feels may interfere with the patient’s ability to give informed consent or participate in the procedures or evaluations of the study
* History of major non-compliance to medication
* Evidence of CNS leukemia
* Uncontrolled viral infection with known HIV or Hepatitis type B or C
* Currently active gastrointestinal disease (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome, or small bowel resection), or other disease, that prevents the patient from absorbing or taking oral medication
* Any other concurrent severe and/or uncontrolled medical conditions (eg. acute or chronic liver disease, infection, pulmonary disease) that in the opinion of the investigator could potentiate unacceptable safety risks or jeopardize compliance with the protocol
* Males with a female partner of childbearing potential do not agree to use at least 2 effective contraceptive methods throughout the study and for 6 months following the date of last dose

Study design
Purpose of the study
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients will have to pass screening procedures and meet eligability criteria. Groups of 3 patients will be entered at each dose level of Everolimus. Dose escalation/stopping rules to determine the maximum tolerated dose (MTD) are as follows:

Number in cohort experiencing DLT by day 42 Action
2/3 or 3/3 No further dose escalation. Previous level is defined as MTD
0/3 Dose escalate to next level
1/3 Expand cohort to 6 patients
1/6 or 2/6 Dose escalate to next level
>2/6 No further dose escalation. Previous level is defined as MTD

Note that if dose escalation is still indicated at the highest dose level, then the MTD is at or above the last dose level. If the trial stops at the first dose, then the MTD is below the first dose level. In either of the above cases, the MTD is not determined from the trial.

Once the maximum dose level has been identified, a dose expansion phase will continue recruiting patients at the MTD until a total of 40 patients for the entire study is accrued.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not Applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?

Intervention assignment
Single group
Other design features
Phase 1 / Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment status
Date of first participant enrolment
Date of last participant enrolment
Date of last data collection
Sample size
Accrual to date
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 257918 0
Self funded/Unfunded
Name [1] 257918 0
Address [1] 257918 0
Country [1] 257918 0
Primary sponsor type
Alfred Hospital
Commercial Road
VIC 3004
Secondary sponsor category [1] 257107 0
Name [1] 257107 0
Address [1] 257107 0
Country [1] 257107 0

Ethics approval
Ethics application status
Ethics committee name [1] 259932 0
The Alfred Human Research Ethics Committee
Ethics committee address [1] 259932 0
Alfred Hospital
Commerical Road
Melbourne VIC 3004
Ethics committee country [1] 259932 0
Date submitted for ethics approval [1] 259932 0
Approval date [1] 259932 0
Ethics approval number [1] 259932 0

Brief summary
To examine the safety and tolerability of Everolimus in combination with 5-azacitidine in Acute Myeloid Leukaemia.
Trial website
Trial related presentations / publications
Public notes

Principal investigator
Name 31823 0
Address 31823 0
Country 31823 0
Phone 31823 0
Fax 31823 0
Email 31823 0
Contact person for public queries
Name 15070 0
Shelley Firth
Address 15070 0
Level 1 South Block
The Alfred Hospital
Commercial Road
Melbourne VIC 3004
Country 15070 0
Phone 15070 0
+61 3 90763928
Fax 15070 0
Email 15070 0
Contact person for scientific queries
Name 5998 0
Dr Andrew Wei
Address 5998 0
Level 1 South Block
The Alfred Hospital
Commercial Road
Melbourne VIC 3004
Country 5998 0
Phone 5998 0
+61 3 90763928
Fax 5998 0
Email 5998 0

No information has been provided regarding IPD availability
Summary results
No Results