CKD-581 + Lenalidomide + Dexamethasone in Patients With Previously Treated Multiple Myeloma

A Phase I, Open-Label, Multi-Center Study of CKD-581 in Combination With Lenalidomide and Dexamethasone in Patients With Previously Treated Multiple Myeloma

This study is to determine the maximum tolerated dose(MTD) and recommened phase 2 dose(RP2D) based on dose limiting toxicity(DLT), and to evaluate safety and pharmacokinetics(PK) profile of a single agent CKD-581 injection in Combination with Lenalidomide and Dexamethasone in patients with Previously Treated Multiple Myeloma.

Study Overview

• Status: Unknown
• Conditions: Myeloma, Multiple
• Intervention / Treatment: Drug: Treat Regimen

Detailed Description

This is an open label, dose escalation study. Cohort of 3~6 patients receive escalation doses of CKD-516 until the maximum tolerated dose(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicity.

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gangnam-gu
    • Seoul, Gangnam-gu, Korea, Republic of, 06351
      • Recruiting
      • Samsung Hospital
      • Contact: Ki Hyun Kim, PI
  • Seocho
    • Seoul, Seocho, Korea, Republic of, 06591
      • Recruiting
      • The Catholic University of Korea, Seoul St. Mary's Hospital
      • Contact: Chang-ki Min, PI

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• must have received at least two prior lines of therapy and Diagnosis of symptomatic multiple myeloma(IMWG 2015)
• Eastern Cooperative Oncology Group performance status ≤ 2
• Life expectancy 12 weeks

• must have the following laboratory values within 3 weeks prior to first dose of study drug

  • absolute neutrophil count(ANC) ≥ 1,500 mm3
  • platelet count(PLT)≥ 100,000 mm3
  • Hb ≥ 9.0g/dL
  • AST(SGOT) and ALT(SGPT) ≤ 3 x upper limit of normal(UNL)
  • Serum bilirubin ≤ 1.5 x ULN (but, Gilbert syndrome ≤ 3 x UNL)
  • Creatinin Clearance(CrCl) ≤ 50mL/min

• One more measureable disease following values

  • Serum M-protein ≥ 1g/dL
  • Urine M-Protein ≥ 200mg/24hr
  • in that case serum M-protein, urine M-Protein nonmeasurable and FLC ratio abnormal, Serum free light chain(FLC) level ≥ 100mg/L(≥10mg/dL)
• more than 24 weeks prior to last lenalidomide dose
• must have signed the consent form

Exclusion Criteria:

• Patients with CNS disease
• Patients with clinically significant heart disease within 24weeks prior to first dose of study drug
• patients with clinically significans abnormal EKG, echocardiography at screening
• patients with patients with embolism within 24 weeks
• patients with active hepatitis, HIV positive(exception, non active hepatitis)
• peripheral neuropathy ≥ CTCAE grade 2 within 2 weeks prior to first dose of study drug
• Patients with clinically significant disease
• Patients with a prior malignancy with in the last 3 years except adequately treated basal cell or squamous cell or skin cancer, in situ cervical cancer
• Patients who have received surgery, chemotherapy, radiation therapy or immunotherapy or any other investigational drugs ≤ 4 weeks prior to first dose of study drug and during treatment period
• Patients who can not anticoagulate
• Patients who have received dexamethasone >10mg/day within 2week prior to first dose of study drug and during treatment period
• Women who are pregnant or breast feeding or women of childbearing potential not using an effective method of birth control. Male patients whose sexual partners are not using effective birth control.
• patients with hypersensitive reaction of lenalidomide or dexamethasone

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: Treat Regimen; CKD-581(investigational Drug) Lenalidomide Dexamethasone	Drug: Treat Regimen; CKD-581(investigational Drug): on days 1, 8, 15 of repeated 28day cycles Lenalidomide: on days 1~21 of repeated 28 day cycles Dexamethasone: administrated once weekly every 28day cycles; Other Names: CKD-581 lenalidomide dexamethasone regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MTD	Maximum Tolerated Dose	Up to 28 days(for 1st cycle)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics(Cmax)	Pharmacokinetics	1st Cycle day1: up to 24hr

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate(ORR)	Objective Response Rate(ORR) of participants as assessed by IMWG uniform response criteria(2011) every 4weeks	Average time period between the start day of induction therapy and the day of relapse or progression or death, whichever occurs firstly, up to 1year
Progression Free Survival(PFS)	Progression Free Survival(PFS) of participants as assessed by IMWG uniform response criteria(2011) every 4weeks	Average time period between the start day of induction therapy and the day of relapse or progression or death, whichever occurs firstly, up to 1year
Overall Survival(OS)	Overall Survival(OS) of participants as assessed by IMWG uniform response criteria(2011) every 4weeks	Average time period between the start day of induction therapy and the day of death, due to any cause, up to 1year
Duration of Response(DOR)	Duration of Response(DOR) of participants as assessed by IMWG uniform response criteria(2011) every 4weeks	Average time period between the day of first achievement of response and the day of first relapse or progression, up to 1year
Pharmacokinetics(T1/2)	Pharmacokinetics	1st Cycle day1: up to 24hr
Pharmacokinetics(CL)	Pharmacokinetics	1st Cycle day1: up to 24hr
Pharmacokinetics(AUClast)	Pharmacokinetics	1st Cycle day1: up to 24hr
Pharmacokinetics(AUCinf)	Pharmacokinetics	1st Cycle day1: up to 24hr
Pharmacokinetics(Vd)	Pharmacokinetics	1st Cycle day1: up to 24hr
Pharmacokinetics( MRT)	Pharmacokinetics	1st Cycle day1: up to 24hr
Adverse events	Adverse events will be assessed using CTCAE criteria.	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Chong Kun Dang Pharmaceutical
• Investigators: Principal Investigator: Chanki Min, The Catholic University of Korea

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2017
• Primary Completion (Anticipated): June 30, 2020
• Study Completion (Anticipated): September 30, 2021

Study Registration Dates

• First Submitted: May 10, 2017
• First Submitted That Met QC Criteria: May 10, 2017
• First Posted (Actual): May 12, 2017

Study Record Updates

• Last Update Posted (Actual): February 24, 2020
• Last Update Submitted That Met QC Criteria: February 20, 2020
• Last Verified: February 1, 2020

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; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Histone Deacetylase Inhibitors; Dexamethasone; Lenalidomide; CKD-581
• Other Study ID Numbers: 133MM16016

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