Phase 1/2 Study of CG200745 PPA for Myelodysplastic Syndrome

Study Overview
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Brief Summary
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<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.

Detailed Description
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<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.

Official Title
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A Phase I/II Study of CG200745 PPA to Determine the Maximum Tolerated Dose and Evaluate the Safety and Efficacy in Patients With Myelodysplastic Syndrome (MDS) Who Failed to Respond to Prior Hypomethylating Therapy

Conditions
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Myelodysplastic Syndrome

Intervention / Treatment
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* Drug: CG200745 PPA


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CG200745 PPA<br>CG200745 PPA intravenously daily for first 5 consecutive days per cycle (4 weeks) | Drug: CG200745 PPA<br>* CG200745 PPA intravenously daily for first 5 consecutive days per cycle (4 weeks)<br>* Other names: CG200745 PPA (phosphoric acid);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | ORR is the proportion of the subjects with Complete Response (CR), Partial Response (PR), marrow CR (mCR), and hematological improvement (HI) in comparison to the total subjects | up to 6 cycles (each cycle is 28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve [AUC] | Pharmacokinetics (PK) parameter | Part I, Cycle 1, Day 1, up to 6 days | 
| Maximum Plasma Concentration [Cmax] | Pharmacokinetics (PK) parameter | Part I, Cycle 1, Day 1, up to 6 days | 
| Adverse Event | Safety parameter | up to 6 cycles | 
| Clinical laboratory tests | Safety parameter | up to 6 cycles |