Myelodysplastic Syndrome
Conditions
Brief summary
\<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
\<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.
Interventions
DRUGCG200745 PPA
CG200745 PPA intravenously daily for first 5 consecutive days per cycle (4 weeks)
Sponsors
CrystalGenomics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | up to 6 cycles (each cycle is 28 days) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration [Cmax] | Part I, Cycle 1, Day 1, up to 6 days | Pharmacokinetics (PK) parameter |
| Area Under the Curve [AUC] | Part I, Cycle 1, Day 1, up to 6 days | Pharmacokinetics (PK) parameter |
| Adverse Event | up to 6 cycles | Safety parameter |
| Clinical laboratory tests | up to 6 cycles | Safety parameter |
Countries
South Korea
Outcome results
None listed