Safety and Pharmacokinetic Profile of CKD-581

Phase 1

Completed

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Treatment	CKD-581	CKD-581

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose	Up to 28 days (For 1st cycle)

Secondary Outcome Measures

Name	Time	Method
Progression Free survival	up to progression
Pharmacokinetics	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)	PK parameters(AUC, Cmax) of CKD-581 \& metabolites
Objective response rate	every 56 days (every 2 cycle)
Dose Limiting Toxicity	Up to 28 days (For 1st cycle)

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