A Single Arm Pilot Study of Azacitidine in Myelodysplastic Syndrome / Acute Myeloid Leukaemia, With Eltrombopag Support for Thrombocytopenia.
- 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
- Age >18 years
- ECOG score 0-2 at screening
- Life expectancy ≥12 weeks
- Ability to comply with the adequate contraception in patients of childbearing
- Subjects with the diagnosis acute promyelocytic leukaemia
- Prior treatment with azacitidine or any other methyl-transferase inhibitor (e.g.
- 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
- 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
- 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
- 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.