Inclusion Criteria:

1. Histologically or cytological documented diagnosis of myelodysplastic syndrome (MDS).
2. Male or female patients aged >= 18 years old.
3. MDS patients who have failed hypomethylating (azacitabine or decitabine) therapy.
4. Patients with 5q-cytogenic abnormalities must also have progressed on or been intolerant to lenalidomide.
5. Patients with up to and including 30% blasts (FAB RAEB-T) will be eligible to enroll.
6. CMML with >= 5% blasts will be eligible to enroll.
7. ECOG PS 0, 1 or 2.

8. Laboratory values must be as follows:

   Bilirubin <= 1.5 mg/dL AST/SGOT <= 2.5 x ULN ALT/SGPT Creatinine <= 2.0 mg/dL or 24-hour Creatinine Clearance >= 50 ml/min Albumin >= 3 g/dL Potassium >= lower limit normal (LLN) Phosphorous >= LLN Calcium >= LLN Magnesium >= LLN

9. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to start of treatment.
10. Life expectancy >= 12 weeks.
11. Accessible for treatment and follow-up.
12. All patients must be able to understand the nature of the study and give written informed consent prior to study entry.

Exclusion Criteria:

1. Prior treatment with an HDAC inhibitor.
2. Prior intensive chemotherapy or high dose ara-C (>= 1 gm/m2)
3. More than one prior single agent chemotherapy regimen. Prior hydroxyurea for cytoreduction will be permitted however.

4. Impaired cardiac function including any of the following:

   • Screening ECG with a QTc > 450 msec.
   • Congenital long QT syndrome.
   • History of sustained ventricular tachycardia.
   • Any history of ventricular fibrillation or torsades de pointes.
   • Bradycardia defined as heart rate < 50 beats per minutes. Patients with a pacemaker and heart rate >= 50 beats per minute are eligible.
   • Myocardial infarction or unstable angina within 6 months of study entry.
   • Congestive heart failure (NY Heart Association class III or IV.
   • Right bundle branch block and left anterior hemiblock (bifasicular block).
   • Uncontrolled hypertension (systolic blood pressure [BP], >180 or diastolic BP >100mm Hg) or uncontrolled cardiac arrhythmias.
   • Atrial fibrillation or flutter.
5. Active CNS disease, including leptomeningeal metastases.
6. Known diagnosis of human immunodeficiency virus (HIV) infection.
7. Unresolved diarrhea > CTCAE grade 1.
8. Chemotherapy, investigational drug therapy, major surgery < 4 weeks prior to starting study drug or patients that have not recovered from side effects of previous therapy.
9. Patient is < 5 years free of another primary malignancy except if the other primary malignancy is not currently clinically significant or requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
10. Concomitant use of any anti-cancer therapy or radiation therapy.
11. Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not willing to use a double barrier method of contraception during the study and 3 months after the end of treatment. One of these methods of contraception must be a barrier method. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 7 days of the first administration of oral LBH589.
12. Male patients whose sexual partners are WOCBP not using a double method of contraception during the study and 3 months after the end of treatment. One of these methods must be a condom.
13. Patients with gastrointestinal (GI) tract disease, causing the inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis).
14. Other concurrent severe, uncontrolled systemic fungal, bacterial, viral or other infection or intercurrent illness, including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
15. Patients with uncontrolled coagulopathy.
16. Abnormal thyroid function (TSH or free T4) detected at screening. Patients with known hypothyroidism who are stable on thyroid replacement are eligible.