A Single Arm Pilot Study of Azacitidine in Myelodysplastic Syndromes (MDS) / Acute Myeloid Leukaemia (AML), With Eltrombopag Support for Thrombocytopenia (Aza-E)

This is an interventional treatment trial for Myelodysplastic Syndromes (MDS) Read More

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.

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.