A Phase Ib Study of Panobinostat (LBH589) in Combination With 5-Azacitidine for Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML) or Acute Myeloid Leukemia (AML) Patients

A Phase Ib, Open-label, Multi-center, Dose-escalation Study of Oral Panobinostat (LBH589) Administered With 5-Azacitidine (Vidaza®) in Adult Japanese Patients With Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML) or Acute Myeloid Leukemia (AML)

The purpose of this study is to confirm the safety and tolerability of oral panobinostat (PAN) in combination with a fixed dose of 5-Azacitidine (5-Aza) in adult Japanese patients with Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML) or Acute Myeloid Leukemia (AML).

Inclusion Criteria:

1. Japanese patients who are candidates for treatment with 5-Aza and present with one of the following:

   • intermediate-2 or high-risk MDS according to the International Prognostic Scoring System (IPSS). OR
   • AML with multilineage dysplasia and maximum of 30% blasts (former RAEB-T according to FAB) OR CMML

2. Patient has an ECOG performance status of ≤ 2

3. Patients must have the following laboratory values unless elevations are considered due to MDS or leukemia: AST/SGOT and/or ALT/SGPT ≤ 2.5 x ULN; serum creatinine ≤ 1.5 x ULN; serum bilirubin (total and direct) ≤ 2 x ULN; electrolyte panel without clinically relevant abnormalities

Exclusion Criteria:

1. Patient who is planned for or has history of hematopoietic stem-cell transplantation (HSCT)
2. Patients with relapsed/refractory AML
3. Patient is receiving concurrent anti-cancer therapy
4. Patient has received prior treatment with deacetylase inhibitors (DACi)
5. Patient has received prior treatment with 5-Aza or 6-aza-2'-deoxycytidine (decitabine)

7. Patient has shown suspected hypersensitivity to 5-Aza or Mannitol 8. Patients with impaired cardiac function 9. Patient taking medications with relative risk of prolonging the QT interval or inducing Torsade de pontes if such treatment cannot be discontinued or switched to a different medication prior to starting study treatment 10. Patients with clinical evidence of relevant mucosal or internal bleeding 11. Patient has any other concurrent severe and/or uncontrolled medical conditions

Other protocol-defined inclusion/exclusion criteria may apply