Phase 1/2 Study of CG200745 PPA for Myelodysplastic Syndrome

Myelodysplastic Syndrome Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02737462
• Other study ID #: CG200745-2-02
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: June 2016
• Est. completion date: December 2023

Study information

• Verified date: September 2023
• Source: CrystalGenomics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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% 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 36
• Est. completion date: December 2023
• Est. primary completion date: December 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

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

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center, Samsung Medical Center, Seoul National University Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
CrystalGenomics, Inc.

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Area Under the Curve [AUC]	Pharmacokinetics (PK) parameter	Part I, Cycle 1, Day 1, up to 6 days
Secondary	Maximum Plasma Concentration [Cmax]	Pharmacokinetics (PK) parameter	Part I, Cycle 1, Day 1, up to 6 days
Secondary	Adverse Event	Safety parameter	up to 6 cycles
Secondary	Clinical laboratory tests	Safety parameter	up to 6 cycles