Phase 1/2 Study of CG200745 PPA for Myelodysplastic Syndrome

\<Part I - Phase I trial\> The phase I clinical trial is to identify the MTD (Maximum Tolerated Dose) and DLT (Dose Limiting Toxicity) of CG200745 PPA. Initial dose of CG200745 PPA is 150 mg/m\^2, and it will be extended to 225 mg/m\^2, 300 mg/m\^2 or it will be reduced to 75 mg/m\^2 based on the results of the cohort of 3 to 6 subjects per dose level.

Based on the 3+3 dose escalation study design, CG200745 PPA is to be administered according to the dose level. Each cohort consists of 3 or 6 subjects.

\<Part II - Phase II trial\> In the phase II clinical trial, the subjects will be administered with the dose which is to be identified as a recommended dose based on the results of Phase I study. Each cycle consisted of 28 days, same as the phase I. The entire treatment period is 6 cycles and tumor assessment is to be evaluated at the end of every 2 cycles.

\<Part I - Phase I trial\> The phase I clinical trial is to identify the MTD and DLT of CG200745 PPA. Initial dose of CG200745 PPA is 150 mg/m\^2, and it will be extended to 225 mg/m\^2, 300 mg/m\^2 or it will be reduced to 75 mg/m\^2 based on the results of the cohort of 3 - 6 subjects per dose level.

Based on the 3+3 dose escalation study design, CG200745 PPA is to be administered as in four different cohorts according to the dose level. Each cohort consists of 3 or 6 subjects.

* Dose Level -1: CG200745 PPA 75 mg/m\^2 x 5 (375 mg/m\^2/cycle) / -50%
* Dose Level 1: CG200745 PPA 150 mg/m\^2 x 5 (750 mg/m\^2/cycle) / initial base dose
* Dose Level 2: CG200745 PPA 225 mg/m\^2 x 5 (1,125 mg/m\^2/cycle) / 50%
* Dose Level 3: CG200745 PPA 300 mg/m\^2 x 5 (1,500 mg/m\^2/cycle) / 33%

\<Part II - Phase II trial\> In the phase II clinical trial, the subjects will be administered with the dose which is to be identified as a recommended dose based on the results of Phase I study. Each cycle consisted of 28 days, same as the phase I. The entire treatment period is 6 cycles and tumor assessment is to be evaluated at the end of every 2 cycles.

Eligibility Criteria:
Inclusion Criteria:

* Ages: 20 years and above
* Patient with MDS according to French-American-British (FAB) classification
* Patients who failed to respond to prior hypomethylating agents (5-azacytidine, decitabine)
* Eastern Cooperative Oncology Group (ECOG) performance status: 0-2
* Adequate renal and hepatic function

  * Total serum bilirubin ≤ 3 x Upper Limit Normal (ULN) (except for the case of increased unconjugated bilirubin)
  * Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and Alkaline phosphatase (ALP) \< 3 x ULN
  * Calculated Glomerular Filtration Rate (GFR) ≥ 50
* Fertile patients, except post-menopausal patients (no menstruation for at least 2 years) or proof of surgical sterility, must use effective contraception up to 3 months after the completion or withdrawal of the study.
* Negative pregnancy test
* Patients who understand the overall procedures and requirements of the study

Exclusion Criteria:

* Peripheral or bone marrow blasts: \> 30%
* Less than 4 weeks since major surgery or radiotherapy
* Patient with clinically meaningful and relevant, active Central Nerve System (CNS) disorder
* Patient with active liver disease
* Patient with HIV positive
* Hyper-sensitivity to study drug or similar substances of the drugs
* Prior Histone Deacetylase (HDAC) inhibitor therapy
* Less than 4 weeks since hypomethylating agent or cytotoxic drug therapy
* Less than 4 weeks since immunosuppressive drug therapy
* Patient who participated in another clinical trial within past 4 weeks
* Patient who have severe diseases:

  * Severe cardiovascular diseases (severe or unstable angina, congestive heart failure, myocardial infarction within past 1 year, uncontrolled hypertension and uncontrolled arrhythmia)
  * Neurological or psychiatric disorder
  * Active uncontrolled infection
  * Any other diseases that may interfere with the interpretation of study result (according to the judgment of investigator)
* Pregnancy or lactating
* Patient who is not considered to be appropriate for the study according to the judgment of investigator