Phase 1/2 Study of CG200745 PPA for Myelodysplastic Syndrome
Study Details
Study Description
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/m2, and it will be extended to 225 mg/m2, 300 mg/m2 or it will be reduced to 75 mg/m2 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
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/m2, and it will be extended to 225 mg/m2, 300 mg/m2 or it will be reduced to 75 mg/m2 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.
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Dose Level -1: CG200745 PPA 75 mg/m2 x 5 (375 mg/m2/cycle) / -50%
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Dose Level 1: CG200745 PPA 150 mg/m2 x 5 (750 mg/m2/cycle) / initial base dose
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Dose Level 2: CG200745 PPA 225 mg/m2 x 5 (1,125 mg/m2/cycle) / 50%
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Dose Level 3: CG200745 PPA 300 mg/m2 x 5 (1,500 mg/m2/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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CG200745 PPA CG200745 PPA intravenously daily for first 5 consecutive days per cycle (4 weeks) |
Drug: CG200745 PPA
CG200745 PPA intravenously daily for first 5 consecutive days per cycle (4 weeks)
Other Names:
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Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- Area Under the Curve [AUC] [Part I, Cycle 1, Day 1, up to 6 days]
Pharmacokinetics (PK) parameter
- Maximum Plasma Concentration [Cmax] [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
Eligibility Criteria
Criteria
Inclusion Criteria:
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Ages: 20 years and above
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Patient with MDS according to French-American-British (FAB) classification
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Patients who failed to respond to prior hypomethylating agents (5-azacytidine, decitabine)
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Eastern Cooperative Oncology Group (ECOG) performance status: 0-2
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Adequate renal and hepatic function
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Total serum bilirubin ≤ 3 x Upper Limit Normal (ULN) (except for the case of increased unconjugated bilirubin)
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Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and Alkaline phosphatase (ALP) < 3 x ULN
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Calculated Glomerular Filtration Rate (GFR) ≥ 50
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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.
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Negative pregnancy test
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Patients who understand the overall procedures and requirements of the study
Exclusion Criteria:
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Peripheral or bone marrow blasts: > 30%
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Less than 4 weeks since major surgery or radiotherapy
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Patient with clinically meaningful and relevant, active Central Nerve System (CNS) disorder
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Patient with active liver disease
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Patient with HIV positive
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Hyper-sensitivity to study drug or similar substances of the drugs
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Prior Histone Deacetylase (HDAC) inhibitor therapy
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Less than 4 weeks since hypomethylating agent or cytotoxic drug therapy
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Less than 4 weeks since immunosuppressive drug therapy
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Patient who participated in another clinical trial within past 4 weeks
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Patient who have severe diseases:
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Severe cardiovascular diseases (severe or unstable angina, congestive heart failure, myocardial infarction within past 1 year, uncontrolled hypertension and uncontrolled arrhythmia)
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Neurological or psychiatric disorder
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Active uncontrolled infection
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Any other diseases that may interfere with the interpretation of study result (according to the judgment of investigator)
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Pregnancy or lactating
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Patient who is not considered to be appropriate for the study according to the judgment of investigator
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Asan Medical Center, Samsung Medical Center, Seoul National University Hospital | Seoul | Korea, Republic of |
Sponsors and Collaborators
- CrystalGenomics, Inc.
Investigators
- Principal Investigator: Je-Hwan Lee, M.D., PhD., Asan Medical Center
- Principal Investigator: Jun Ho Jang, M,D., Ph.D., Samsung Medical Center
- Principal Investigator: Sung-soo Yoon, M,D., Ph.D., Seoul National University Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CG200745-2-02