phase 1/2 study of cg200745 ppa for myelodysplastic syndrome

Conditions: Myelodysplastic Syndrome

Summary: \ 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. \ 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.

\ 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% \ 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