Safety and Pharmacokinetic Profile of CKD-581

Study Overview
=================
Brief Summary
-----------------
This study is to determine the maximum tolerated dose (MTD), dose limiting toxicity (DLT), safety and pharmacokinetics (PK) profile of a single agent CKD-581 injection in patients with Lymphoma failed to standard therapy. The usefulness of the this regimen is evaluated by response rate, progression free survival.

Detailed Description
-----------------
Recently, the role of transcriptional repression through epigenetic modulation in carcinogenesis has been clinically validated with several inhibitors of histone deacetylases and DNA methyltransferases. It has long been recognized that epigenetic alterations of tumor suppressor genes was one of the contributing factors in carcinogenesis. Inhibitors of histone deacetylase (HDAC) de-repress genes that subsequently result in growth inhibition, differentiation and apoptosis of cancer cells. CKD-581 is developed for HDAC inhibitors. Such as to determine the maximum tolerated dose (MTD), dose limiting toxicity (DLT), safety and pharmacokinetics (PK) profile of a single agent CKD-581 injection in patients with Lymphoma failed to standard therapy.

Official Title
-----------------
Phase I Clinical Trial to Assess the Safety and Pharmacokinetic Profile of CKD-581 in Patients With Lymphoma or Multiple Myeloma Failed to Standard Therapy

Conditions
-----------------
Lymphoma, Multiple Myeloma

Intervention / Treatment
-----------------
* Drug: CKD-581


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 20 years and older Histologically or cytologically confirmed Lymphoma or Multiple myeloma that have failed to standard therapy or for which no life prolonging treatment exists ECOG(Eastern cooperative oncology) performance status ≤ 2 Life expectancy 12 weeks Hematopoietic: ANC(Absolute Neutrophil Count) ≥ 1,500/mm3, Platelet count(PLT) ≥ 100,000/mm3, Hemoglobin ≥ 9.0g/dL Hepatic: Total bilirubin > 1.5×upper limit of normal(except Gilbert's syndrome patients), aspartate aminotransferase(AST) > 3×upper limit of normal, alanine aminotransferase(ALT) > 3×upper limit of normal(AST, ALT ≤ 5.0×ULN in case of liver metastases) Renal: serum creatinine ≤ 1.5×upper limit of normal Serum calcium ≤ upper limit of normal (If the Multiple myeloma only) Signed a written informed consent Exclusion Criteria: Have symptoms with Brain metastases History of Ischemic heart disease(e.g., myocardial infarction, unstable angina pectoris) or Clinically significant heart disease such as NYHA Class III and IV Congestive atrial arrhythmias, within 6 months prior to first dose of study drug Acute infection or blooding tendencies that would preclude study compliance Other psychiatric disorders or other conditions that would preclude study compliance Receiving antitumor therapy(surgery, immunotherapy or chemotherapy) within 4 weeks prior to first dose of study drug(6 weeks for nitrosoureas and mitomycin C, 2 weeks for radiation therapy) Other concurrent antitumor therapy Have Cardiac disease by nature Administration history of Histone Deacetylase Inhibitor History of Serious hypersensitivity or allergy Pregnant or nursing, active serum pregnancy test. Fertile patients must use effective contraception Participation in a clinical trial within 4 weeks of first dose of study drug

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>CKD-581 | Drug: CKD-581<br>* CKD-581 qd for Day 1, 8 and 15 every 28days/Cycle<br>* Other names: Histone Deacetylase Inhibitor;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose |  | Up to 28 days (For 1st cycle) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicity |  | Up to 28 days (For 1st cycle) | 
| Pharmacokinetics | PK parameters(AUC, Cmax) of CKD-581 & metabolites | 0, 0.25, 1, 1.5, 2, 2.25, 2.5, 3, 3.5, 4, 6, 8, 12, 24 hrs post dose(1st cycle Day1, 15) | 
| Objective response rate |  | every 56 days (every 2 cycle) | 
| Progression Free survival |  | up to progression |