Panobinostat with 5-azacytidine in patients with untreated high risk Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukaemia (AML).

Patients will receive induction therapy with 6 cycles of 5-azacytidine in combination with panobinostat. All patients will receive azacitidine at a dose of 75mg/m2 administered subcutaneously. Azacitidine will be given days 1-5 of each 28 day cycle. Panobinostat will commence at a dose of 10mg for Cohort 1 and will increase by 10mg for each subsequent Cohort. Panobinostat will be given orally on Days 5, 8, 10, 12, 15, 17 and 19 of each 28 days cycle. All patients not experiencing disease progression and completing 6 cycles of induction therapy with evidence of disease response (HI: haematological improvement; PR: partial remission; or, CR: complete remission) and without unacceptable toxicity will continue treatment with 5-azacytidine and panobinostat for a further period dependent on their level of response to induction therapy. Patients achieving a CR during induction will receive a further 3 cycles of combination therapy with 5-azacytidine and panobinostat (CR + 3 cycles) before continuing on panobinostat maintenance therapy. Patients achieving HI or PR with induction will continue on combination therapy with 5-azacytidine and panobinostat as long as they exhibit no evidence of disease progression. If with further therapy they subsequently achieve a CR they will receive a further 3 cycles of combination therapy with 5-azacytidine and panobinostat (CR + 3 cycles) before continuing on panobinostat maintenance therapy. All patients may remain on therapy until they experience unacceptable toxicity that precludes further treatment, disease progression, and/or at the discretion of the investigator.