A Single Arm Pilot Study of Azacitidine in Myelodysplastic Syndromes (MDS) / Acute Myeloid Leukaemia (AML), With Eltrombopag Support for Thrombocytopenia (Aza-E)
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.
Myelodysplastic Syndromes (MDS)
Acute Myeloid Leukaemia (AML)
Drug: Azacitidine and eltrombopag
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Single Arm Pilot Study of Azacitidine in Myelodysplastic Syndrome / Acute Myeloid Leukaemia, With Eltrombopag Support for Thrombocytopenia.|
- Number of events of non-haematological toxicities related to the combination of eltrombopag and azacitidine [ Time Frame: At 6 cycles of therapy (approx 6 months) ] [ Designated as safety issue: Yes ]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
- Number of patients with improved platelet counts and the dose at which this may be achieved. [ Time Frame: Approximately 2.5 years after the last accrued patient completes study treatment ] [ Designated as safety issue: No ]
- 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 [ Time Frame: Approximately 2.5 years after last accrued patient completes study treatment ] [ Designated as safety issue: No ]
|Study Start Date:||December 2010|
|Estimated Study Completion Date:||May 2015|
|Estimated Primary Completion Date:||May 2014 (Final data collection date for primary outcome measure)|
Experimental: Azacitidine and Eltrombopag
Vidaza (azacitidine) Revolade (eltrombopag)
Drug: 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01488565
|Peter MacCallum Cancer Centre|
|East Melbourne, Victoria, Australia, 3002|
|Malvern, Victoria, Australia, 3144|
|Principal Investigator:||Michael Dickinson, Dr||Peter MacCallum Cancer Centre, Australia|