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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01488565




Registration number
NCT01488565
Ethics application status
Date submitted
29/11/2011
Date registered
8/12/2011
Date last updated
15/02/2016

Titles & IDs
Public title
A Single Arm Pilot Study of Azacitidine in Myelodysplastic Syndromes (MDS) / Acute Myeloid Leukaemia (AML), With Eltrombopag Support for Thrombocytopenia
Scientific title
A Single Arm Pilot Study of Azacitidine in Myelodysplastic Syndrome / Acute Myeloid Leukaemia, With Eltrombopag Support for Thrombocytopenia.
Secondary ID [1] 0 0
10/78
Universal Trial Number (UTN)
Trial acronym
Aza-E
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelodysplastic Syndromes (MDS) 0 0
Acute Myeloid Leukaemia (AML) 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
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Azacitidine and eltrombopag

Experimental: Azacitidine and Eltrombopag - Vidaza (azacitidine) Revolade (eltrombopag)


Treatment: Drugs: Azacitidine and eltrombopag
Standard: azacitidine D1-5, 8&9, until loss of clinical benefit. Experimental: eltrombopag at a dose ranging from 50-300mg for 6 months, continuing only in those deriving clinical benefit.

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

Outcomes
Primary outcome [1] 0 0
Number of events of non-haematological toxicities related to the combination of eltrombopag and azacitidine - The number of events of Grade III/IV non-haematological toxicities will be measured based on the possibly, probably or definitely relatedness to the combination of eltrombopag and azacitidine
Timepoint [1] 0 0
At 6 cycles of therapy (approx 6 months)
Secondary outcome [1] 0 0
Number of patients with improved platelet counts and the dose at which this may be achieved.
Timepoint [1] 0 0
Approximately 2.5 years after the last accrued patient completes study treatment
Secondary outcome [2] 0 0
Correlation of the laboratory findings with the response of the combination of 5-azacitidine and eltrombopag in patients with MDS and low marrow blast count AML
Timepoint [2] 0 0
Approximately 2.5 years after last accrued patient completes study treatment

Eligibility
Key inclusion criteria
- Patients with low platelet count (<=150 x109/L)and in addition disease diagnosis of
either MDS, or nonproliferative CMML or low marrow blast count AML not suitable for
induction chemotherapy

- Age >18 years

- ECOG score 0-2 at screening

- Life expectancy =12 weeks

- Ability to comply with the adequate contraception in patients of childbearing
potential.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Subjects with the diagnosis acute promyelocytic leukaemia

- Prior treatment with azacitidine or any other methyl-transferase inhibitor (e.g.
decitabine)

- Prior treatment with eltrombopag, romiplostim, or other TPO-receptor agonist

- AML or MDS requiring cytoreductive therapy (eg hydroxyurea, ara-c, thioguanine etc) in
the month prior to study entry

- Known uncontrolled medical conditions which may compromise participation in this study
including but not limited to:

- Poorly controlled congestive heart failure: ejection fraction <30% measured in
past 6 months) or NYHA class IV

- Arrhythmia known to increase the risk of thromboembolic events.

- Unstable angina or an ischaemic cardiac event requiring hospital admission in the
previous 12 months.

- Unresolved GI disease that may significantly alter the absorption of eltrombopag

- Known pro-thrombotic condition as defined by a history =1 unprovoked deep venous
thrombosis or pulmonary embolism, or any DVT/PE with a procoagulant condition screen
suggesting the presence of a procoagulant condition (prothrombin gene mutation
homozygosity, factor V leiden homozygosity, antithrombin deficiency, lupus
anticoagulant syndrome).

- History of Ischaemic neurological event (TIA or stroke) within the preceding 2 years.

- Inadequate renal function (eGFR <30 ml/min by Cockcroft-Gault (C-G) formula, or as
measured by 24 hour urinary creatinine clearance)

- Inadequate hepatic function:

- bilirubin =1.5xULN - =80µmol/L acceptable if attributed to haemolysis,
ineffective erythropoiesis or iron overload). This applies also for patients with
Gilbert's Syndrome.

- AST or ALT =2xULN (=3xULN acceptable if attributed to transfusion-associated iron
overload)

- Patients with known liver cirrhosis.

- Other concurrent severe and/or uncontrolled medical conditions including a history of
malignancy other than MDS/AML in the preceding 2 years requiring chemotherapy and/or
radiotherapy. Non melanotic skin cancers requiring low dose local radiotherapy or
topical agents are allowed on study if considered clinically stable or healed.

- Women who are pregnant or breast-feeding.

- Treatment with growth factors such as erythropoietin, GCSF or stem cell factor in the
21 days prior to commencement of study therapy.

- Active or uncontrolled infections.

- Subjects with known HIV infection.

- Has any other clinically important abnormalities as determined by the investigator
that may interfere with his or her participation in or compliance with the study

- Bone marrow fibrosis that leads to an inability to aspirate marrow for quality
cytological assessment, termed a "dry tap".

- Presence of any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up schedule. This
condition must be discussed with the patient prior to signing consent and registration
in the trial.

- Splenomegaly >14cm on the screening ultrasound examination.

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 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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
Peter MacCallum Cancer Centre - East Melbourne
Recruitment hospital [2] 0 0
Cabrini Hospital - Malvern
Recruitment postcode(s) [1] 0 0
3002 - East Melbourne
Recruitment postcode(s) [2] 0 0
3144 - Malvern

Funding & Sponsors
Primary sponsor type
Other
Name
Peter MacCallum Cancer Centre, Australia
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
GlaxoSmithKline
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Celgene Corporation
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Myelodysplastic Syndrome (MDS) is a disease of the bone marrow characterized by
anemia,neutropenia, and thrombocytopenia (low red blood cell, white blood cell, and platelet
counts). MDS patients with thrombocytopenia who fail standard therapies require regular
platelet transfusions which are expensive and inconvenient, and are a risk for further
serious bleeding complications. The new treatment of MDS using azacitidine has shown to
increase the survival rate of MDS patients including to improve platelet production over
time. However,in the early cycles of treatment with azacitidine,the low platelet counts tend
to exacerbate before they provide any clinical benefit.

Eltrombopag is a drug designed to activate the thrombopoietin receptor. Eltrombopag has been
able to increase platelet counts in healthy Thrombocytopenia Purpura (ITP), a disease where
patients destroy their own platelets very rapidly and thus develop thrombocytopenia.

Eltrombopag is administered orally and is Therapeutic Goods Administration (TGA) approved for
the treatment of thrombocytopenia in patients with chronic ITP who failed to respond to
standard treatment.

This study is a single arm pilot study to evaluate the safety and tolerability of Eltrombopag
in the treatment of low platelet counts in adult subjects with MDS treated using azacitidine
This study also incorporates a correlative laboratory component designed to determined the
mechanism of action of 5-azacitidine +/- Eltrombopag and to determine a baseline profile
which may predict those most responsive. These studies will incorporate gene methylation and
expression, and immunoprofiling.
Trial website
https://clinicaltrials.gov/show/NCT01488565
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Michael Dickinson, Dr
Address 0 0
Peter MacCallum Cancer Centre, Australia
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
Other publications