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Phase 1/2 Study of CG200745 PPA for Myelodysplastic Syndrome

Primary Purpose

Myelodysplastic Syndrome

Status
Active
Phase
Phase 1
Locations
Korea, Republic of
Study Type
Interventional
Intervention
CG200745 PPA
Sponsored by
CrystalGenomics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelodysplastic Syndrome

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Asan Medical Center, Samsung Medical Center, Seoul National University Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CG200745 PPA

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Area Under the Curve [AUC]
Pharmacokinetics (PK) parameter
Maximum Plasma Concentration [Cmax]
Pharmacokinetics (PK) parameter
Adverse Event
Safety parameter
Clinical laboratory tests
Safety parameter

Full Information

First Posted
March 22, 2016
Last Updated
September 11, 2023
Sponsor
CrystalGenomics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02737462
Brief Title
Phase 1/2 Study of CG200745 PPA for Myelodysplastic Syndrome
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 2016 (Actual)
Primary Completion Date
December 2022 (Actual)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CrystalGenomics, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. 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/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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CG200745 PPA
Arm Type
Experimental
Arm Description
CG200745 PPA intravenously daily for first 5 consecutive days per cycle (4 weeks)
Intervention Type
Drug
Intervention Name(s)
CG200745 PPA
Other Intervention Name(s)
CG200745 PPA (phosphoric acid)
Intervention Description
CG200745 PPA intravenously daily for first 5 consecutive days per cycle (4 weeks)
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
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
Time Frame
up to 6 cycles (each cycle is 28 days)
Secondary Outcome Measure Information:
Title
Area Under the Curve [AUC]
Description
Pharmacokinetics (PK) parameter
Time Frame
Part I, Cycle 1, Day 1, up to 6 days
Title
Maximum Plasma Concentration [Cmax]
Description
Pharmacokinetics (PK) parameter
Time Frame
Part I, Cycle 1, Day 1, up to 6 days
Title
Adverse Event
Description
Safety parameter
Time Frame
up to 6 cycles
Title
Clinical laboratory tests
Description
Safety parameter
Time Frame
up to 6 cycles

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Je-Hwan Lee, M.D., PhD.
Organizational Affiliation
Asan Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jun Ho Jang, M,D., Ph.D.
Organizational Affiliation
Samsung Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Sung-soo Yoon, M,D., Ph.D.
Organizational Affiliation
Seoul National University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Asan Medical Center, Samsung Medical Center, Seoul National University Hospital
City
Seoul
Country
Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Phase 1/2 Study of CG200745 PPA for Myelodysplastic Syndrome

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