Safety and Pharmacokinetic Profile of CKD-581

Multiple Myeloma Clinical Trial

— CKD-581  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01580371
• Other study ID #: 133HL/NHL11L
• Status: Completed
• Phase: Phase 1
• First received: April 16, 2012
• Last updated: October 4, 2016
• Start date: May 2012
• Est. completion date: June 2016

Study information

• Verified date: October 2016
• Source: Chong Kun Dang Pharmaceutical
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Ministry of Food and Drug Safety
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: June 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• CKD-581
CKD-581 qd for Day 1, 8 and 15 every 28days/Cycle

Locations

Country	Name	City	State
Korea, Republic of	ASAN Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Chong Kun Dang Pharmaceutical

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose		Up to 28 days (For 1st cycle)	No
Secondary	Dose Limiting Toxicity		Up to 28 days (For 1st cycle)	Yes
Secondary	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)	No
Secondary	Objective response rate		every 56 days (every 2 cycle)	No
Secondary	Progression Free survival		up to progression	No