Clinical trial NCT02737462: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Myelodysplastic Syndrome
Lead sponsor: CrystalGenomics, Inc.
Sponsor class: INDUSTRY
First posted: 2016-04-14
Enrollment: 36
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: up to 6 cycles (each cycle is 28 days)
Secondary outcomes:
measure: Area Under the Curve [AUC]
timeFrame: Part I, Cycle 1, Day 1, up to 6 days
measure: Maximum Plasma Concentration [Cmax]
timeFrame: Part I, Cycle 1, Day 1, up to 6 days
measure: Adverse Event
timeFrame: up to 6 cycles
measure: Clinical laboratory tests
timeFrame: up to 6 cycles
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center, Samsung Medical Center, Seoul National University Hospital
Study officials:
affiliation: Asan Medical Center
name: Je-Hwan Lee, M.D., PhD.
role: PRINCIPAL_INVESTIGATOR
affiliation: Samsung Medical Center
name: Jun Ho Jang, M,D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Seoul National University Hospital
name: Sung-soo Yoon, M,D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: