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Trial registered on ANZCTR


Registration number
ACTRN12610000641099
Ethics application status
Approved
Date submitted
5/08/2010
Date registered
6/08/2010
Date last updated
16/12/2010
Type of registration
Prospectively registered

Titles & IDs
Public title
Eltrombopag therapy for low platelets in patients on azacitidine treatment for myelodysplastic syndrome and acute myeloid leukaemia
Scientific title
A single arm pilot study of azacitidine in myelodysplastic syndrome / acute myeloid leukaemia, with eltrombopag support for thrombocytopenia
Secondary ID [1] 252382 0
nil
Universal Trial Number (UTN)
Trial acronym
AZA-E
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelodysplastic Syndromes (MDS) 257892 0
Low marrow blast count acute myeloid leukaemia (AML) 257893 0
Condition category
Condition code
Blood 258053 258053 0 0
Haematological diseases
Cancer 258054 258054 0 0
Leukaemia - Acute leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Eltrombopag given orally every day for a 1-2 week pre-phase (50mg for a week, with a potential to go straight to combination therapy at 1 week or to maintain eltrombopag at the same dose as monotherapy for a second week in eligible patients, followed by azacitidine with or without eltrombopag. Individualised dose escalation of eltrombopag adapted according to response (dose range from 50-150mg in patients of East Asian extraction, 50-300mg in patients of predominantly non-East Asian extraction). Azacitidine administered by subcutaneous injection 75mg/m2 days 1-5, 8,9 per cycle for 6 cycles, for a total of 54 days treatment, with ongoing azacitidine offered those deriving clinical benefit.
Intervention code [1] 256944 0
Treatment: Drugs
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 258916 0
Grade III/IV non-haematological toxicity possibly, probably or definitely related to the combination of eltrombopag and azacitidine based on clinical assessments.
Timepoint [1] 258916 0
At 6 cycles of therapy (approx 6 months)
Secondary outcome [1] 265078 0
Secondary outcome 1:
To gather preliminary evidence of the clinical efficacy of eltrombopag to improve platelet counts in this setting, and the appropriate dose at which this may be achieved based on data obtained from clinical assessments, up to 4 bone marrow biopsies, and peripheral blood tests.
Timepoint [1] 265078 0
Time point: approximately 2.5 years after the last accrued patient completes study treatment
Secondary outcome [2] 265079 0
To explore laboratory findings to correlate with the response of the combination of 5-azacitidine and eltrombopag in patients with MDS and low marrow blast count AML
Timepoint [2] 265079 0
Time point: 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 (by World Health Organization Criteria, those with refractory anemia with high blast counts and refractory anemia with ringed sideroblasts to also have at least one clinically significant cytopenia), nonproliferative Chronic Myelomonocytic Leukaemia (CMML) or low marrow blast count AML not suitable for induction chemotherapy; Eastern Cooperative Oncology Group (ECOG) 2 or less with life expectancy at least 3 months, adequate contraception and adequate renal and hepatic function; written informed consent
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 5-azacitidine or any other methyl-transferase inhibitor, eltrombopag, romiplostim, or other Trombopoietin T (TPO)-receptor agonist;AML or MDS requiring cytoreductive therapy (eg hydroxyurea, ara-c, thioguanine etc) in the month prior to study entry; known pro-thrombotic condition; history of Ischaemic neurological event (Transient Ischaemic Attack (TIA) or stroke) within the preceding 2 years;active or uncontrolled infections

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
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)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
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)
Recruitment postcode(s) [1] 3120 0
3002

Funding & Sponsors
Funding source category [1] 257395 0
Government body
Name [1] 257395 0
Victorian Cancer Agency
Address [1] 257395 0
12 Victoria St. Carlton
Victoria, Australia, 3053
Country [1] 257395 0
Australia
Funding source category [2] 257396 0
Commercial sector/Industry
Name [2] 257396 0
GlaxoSmithKline Pty Ltd
Address [2] 257396 0
1061 Mountain Highway
Boronia, Victoria, Australia, 3155
Country [2] 257396 0
Australia
Funding source category [3] 257397 0
Commercial sector/Industry
Name [3] 257397 0
Celgene Pty Ltd
Address [3] 257397 0
Celgene Australia Melbourne Level 7, 607 St Kilda Rd. Melbourne, Victoria 3004
Country [3] 257397 0
Australia
Primary sponsor type
Hospital
Name
Peter Mac Callum Cancer Centre
Address
St Andrews Place, East Melbourne Victoria, 3002
Country
Australia
Secondary sponsor category [1] 256642 0
None
Name [1] 256642 0
Address [1] 256642 0
Country [1] 256642 0
Secondary sponsor category [2] 256643 0
None
Name [2] 256643 0
Address [2] 256643 0
Country [2] 256643 0
Other collaborator category [1] 251423 0
Other Collaborative groups
Name [1] 251423 0
Victorian Epigenetic Group
Address [1] 251423 0
Dr Melita Kenealy (coordinator)
Peter MacCallum Cancer Centre
St Andrews Pl. East Melbourne
Victoria 3002
Country [1] 251423 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 259418 0
Peter MacCallum Cancer Centre Ethics Committee
Ethics committee address [1] 259418 0
St Andrews Pl, East Melbourne
Victoria
Ethics committee country [1] 259418 0
Australia
Date submitted for ethics approval [1] 259418 0
06/08/2010
Approval date [1] 259418 0
13/12/2010
Ethics approval number [1] 259418 0
10/78

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 volunteers and in patients with chronic Immune 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
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31477 0
Address 31477 0
Country 31477 0
Phone 31477 0
Fax 31477 0
Email 31477 0
Contact person for public queries
Name 14724 0
Dr Kirsten Herbert
Address 14724 0
c/o Department of Haematology and Medical Oncology, Peter Mac Callum Cancer Centre
Locked Bag 1
A’Beckett Street. Melbourne VIC 8006
Country: Australia
Country 14724 0
Australia
Phone 14724 0
+61 3 9656 1701
Fax 14724 0
Email 14724 0
Kirsten.Herbert@petermac.org
Contact person for scientific queries
Name 5652 0
Dr Kirsten Herbert
Address 5652 0
c/o Department of Haematology and Medical Oncology, Peter Mac Callum Cancer Centre
Locked Bag 1
A’Beckett Street. Melbourne VIC 8006
Country: Australia
Country 5652 0
Australia
Phone 5652 0
+61 3 9656 1701
Fax 5652 0
Email 5652 0
Kirsten.Herbert@petermac.org

No information has been provided regarding IPD availability
Summary results
No Results