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Everolimus (RAD001) in Elderly Patients With Acute Myeloid Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00636922
Recruitment Status : Unknown
Verified February 2013 by Bayside Health.
Recruitment status was:  Active, not recruiting
First Posted : March 17, 2008
Last Update Posted : February 15, 2013
Information provided by (Responsible Party):
Bayside Health

Brief Summary:
The main goal of this study is to assess the safety and tolerability of RAD001 in combination with low-dose cytarabine in acute myeloid leukemia patients unfit for intensive chemotherapy. The secondary goals are to investigate the likely causes of drug response or failure.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: RAD001(Everolimus) Phase 1

Detailed Description:

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 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Dose Finding Study of Everolimus (RAD001) in Elderly Patients With Acute Myeloid Leukemia (AML) Unfit for Intensive Induction Chemotherapy
Study Start Date : February 2010
Estimated Primary Completion Date : July 2013
Estimated Study Completion Date : January 2014

Arm Intervention/treatment
Experimental: Everolimus with 5-azacitidine
Everolimus increasing oral doses days 5-21 each cycle 5-azacitidine 75mg sub cutaneously 7 doses in 21 days
Drug: RAD001(Everolimus)
In this study, 5-azacitidine will be administered sc for 7 doses over 9 days in a 28 day cycle. Everolimus will be administered orally with the first dose starting on day 5 (first Friday) of each cycle and continued until day 21 of each cycle. Patients will be treated with combined azacitidine + Everolimus for a minimum of 6 cycles and until at least 2 cycles after documentation of CR. Upon cessation of azacitidine, the patient will be permitted to take Everolimus maintenance therapy until progression at the investigator's discretion.
Other Name: Everolimus

Primary Outcome Measures :
  1. safety & tolerability [ Time Frame: over 24 cycles of treatment ]
    haematological toxicities (marrow status, neutrophil recovery), non-haematological grade 4 toxicity

Secondary Outcome Measures :
  1. clinical Response [ Time Frame: up to 3 years ]
    measure disease free survival up to 3 years

  2. biomarkers of response [ Time Frame: over length of treatment up to 24 cycles ]
    measure examples of biomarkers of disease response such as gene-specific methylation and phosphorylation status of mTOR targets

  3. patient related outcomes [ Time Frame: during treatment and in followup for up to 3 years ]
    Quality of life questionnaires and treatment related toxicities

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00636922

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Australia, Victoria
BaysideHealth, The Alfred Hospital
Melbourne, Victoria, Australia, 3004
Sponsors and Collaborators
Bayside Health
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Principal Investigator: Andrew Wei, MBBS PhD Bayside Health
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Responsible Party: Bayside Health Identifier: NCT00636922    
Other Study ID Numbers: CRAD001C24112
First Posted: March 17, 2008    Key Record Dates
Last Update Posted: February 15, 2013
Last Verified: February 2013
Keywords provided by Bayside Health:
Acute Myeloid Leukemia
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs