Phase 1/2 Study of CG200745 PPA for Myelodysplastic Syndrome

CrystalGenomics

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Myelodysplastic Syndrome

Treatments: Drug: CG200745 PPA

Study type: Interventional

Funder types: Industry

Identifiers

NCT02737462

CG200745-2-02

Details and patient eligibility

About

<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.

Full 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.

Enrollment: 36 estimated patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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36 participants in 1 patient group

CG200745 PPA

Experimental group

Description:

CG200745 PPA intravenously daily for first 5 consecutive days per cycle (4 weeks)

Treatment:

Drug: CG200745 PPA