Phase 1/2 Study of CG200745 PPA for Myelodysplastic Syndrome

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

<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.

Study Overview

• Status: Active, not recruiting
• Conditions: Myelodysplastic Syndrome
• Intervention / Treatment: Drug: CG200745 PPA

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.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Sangsook Cho, Ph.D.; Phone Number: +1 925 876 1975; Email: scho@cgxinc.com
• Study Contact Backup: Name: Chohee Park; Phone Number: +82 31 628 2872; Email: chpark@cgxinc.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Asan Medical Center, Samsung Medical Center, Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: CG200745 PPA (phosphoric acid)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: 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 record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Actual): December 1, 2022
• Study Completion (Estimated): December 1, 2023

Study Registration Dates

• First Submitted: March 22, 2016
• First Submitted That Met QC Criteria: April 8, 2016
• First Posted (Estimated): April 14, 2016

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 11, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia
• Other Study ID Numbers: CG200745-2-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED