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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00636922




Registration number
NCT00636922
Ethics application status
Date submitted
10/03/2008
Date registered
17/03/2008
Date last updated
15/02/2013

Titles & IDs
Public title
Everolimus (RAD001) in Elderly Patients With Acute Myeloid Leukemia
Scientific title
A Phase I Dose Finding Study of Everolimus (RAD001) in Elderly Patients With Acute Myeloid Leukemia (AML) Unfit for Intensive Induction Chemotherapy
Secondary ID [1] 0 0
CRAD001C24112
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - RAD001(Everolimus)

Experimental: Everolimus with 5-azacitidine - Everolimus increasing oral doses days 5-21 each cycle 5-azacitidine 75mg sub cutaneously 7 doses in 21 days


Treatment: Drugs: 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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
safety & tolerability - haematological toxicities (marrow status, neutrophil recovery), non-haematological grade 4 toxicity
Timepoint [1] 0 0
over 24 cycles of treatment
Secondary outcome [1] 0 0
clinical Response - measure disease free survival up to 3 years
Timepoint [1] 0 0
up to 3 years
Secondary outcome [2] 0 0
biomarkers of response - measure examples of biomarkers of disease response such as gene-specific methylation and phosphorylation status of mTOR targets
Timepoint [2] 0 0
over length of treatment up to 24 cycles
Secondary outcome [3] 0 0
patient related outcomes - Quality of life questionnaires and treatment related toxicities
Timepoint [3] 0 0
during treatment and in followup for up to 3 years

Eligibility
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
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
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)
VIC
Recruitment hospital [1] 0 0
BaysideHealth, The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Bayside Health
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00636922
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Andrew Wei, MBBS PhD
Address 0 0
Bayside Health
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT00636922