Safety and Pharmacokinetic Profile of CKD-581 (CKD-581)

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

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.

Study Overview

• Status: Completed
• Conditions: Lymphoma; Multiple Myeloma
• Intervention / Treatment: Drug: CKD-581

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.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Asan Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Chong Kun Dang Pharmaceutical
• Investigators: Study Chair: Dok Hyun Yoon, Ph.D, 88,Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: April 16, 2012
• First Submitted That Met QC Criteria: April 17, 2012
• First Posted (Estimate): April 19, 2012

Study Record Updates

• Last Update Posted (Estimate): October 6, 2016
• Last Update Submitted That Met QC Criteria: October 4, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Lymphoma; Multiple Myeloma; Neoplasms, Plasma Cell; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Histone Deacetylase Inhibitors; CKD-581
• Other Study ID Numbers: 133HL/NHL11L

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No