A Phase Ib/II Clinical Evaluation of the Safety of Combining the mTOR inhibitor Everolimus with 5-Azacitidine in Acute Myeloid Leukaemia (AML).
- Conditions
- Acute Myeloid LeukaemiaCancer - Leukaemia - Acute leukaemia
- Registration Number
- ACTRN12610001031055
- Lead Sponsor
- Alfred Hospital
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 40
*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
* 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
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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.[Continuously throughout cycle]
- Secondary Outcome Measures
Name Time Method 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.[Contiuously throughout cycle.];To assess biomarkers of response such as gene specific methylation and phosphorylayion status of mTOR targets, from laboratory studies.[Contiuously throughout cycle.];To assess patient related outcomes for patients receiving the Everolimus/5-azacitidine combination via adverse events and quality of life questionnaries.[Contiuously throughout cycle.]