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A Phase I Dose Finding Study of Everolimus (RAD001) in Elderly Patients With Acute Myeloid Leukemia (AML) Unfit for Intensive Induction Chemotherapy

Phase 1
18 Years
Open (Enrolling)
Acute Myeloid Leukemia

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Trial Information

A Phase I Dose Finding Study of Everolimus (RAD001) in Elderly Patients With Acute Myeloid Leukemia (AML) Unfit for Intensive Induction Chemotherapy

A multicentre 2-stage Phase Ib/II trial of 5-Azacitidine combined with Everolimus for AML
patients over the age of 60 or relapsed AML over the age of 18. The MTD and DLT of
5-Azacitidine (7 doses over 9 days) given monthly combined with Everolimus orally for 17
days (day 5-21) each month (1 cycle) for a minimum of 6 cycles and for at least 2 cycles
beyond achievement of CR and for a maximum of 12 cycles. Everolimus maintenance therapy
alone may be continued at investigator's discretion until either progressive disease or dose
limiting toxicity. Groups of 3 patients will be entered at each dose level. 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

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.

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

- 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

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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

safety & tolerability

Outcome Description:

haematological toxicities (marrow status, neutrophil recovery), non-haematological grade 4 toxicity

Outcome Time Frame:

over 24 cycles of treatment

Safety Issue:


Principal Investigator

Andrew Wei, MBBS PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Bayside Health


Australia: Department of Health and Ageing Therapeutic Goods Administration

Study ID:




Start Date:

February 2010

Completion Date:

January 2014

Related Keywords:

  • Acute Myeloid Leukemia
  • Acute Myeloid Leukemia
  • Elderly
  • Unfit
  • Everolimus
  • RAD001
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid