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

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

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 Combination with Bortezomib and Dexamethasone in patients with Previously Treated Multiple Myeloma.

Study Overview

• Status: Unknown
• Conditions: Myeloma, Multiple
• Intervention / Treatment: Drug: CKD-581

Detailed Description

This is an open label, dose escalation study. Cohort of 3~6 patients receive escalation doses of CKD-581 until the maximum toleated dose(MTD) is determined. The MTD is defiend 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
  • Seoul, Korea, Republic of
    • Recruiting
    • Seoul National University Hospital
    • Contact: Sung-Soo Yoon; Phone Number: +82-2-2072-3079; Email: ssysmc@gmail.com

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 one prior lines of therapy and Diagnosis of symptomatic multiple myeloma(IMWG 2014)
• 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

  • ANC(absolute neutrophil count) ≥ 1,500 mm3
  • PLT(platelet count)≥ 100,000 mm3
  • Hb ≥ 8.0g/dL
  • AST(SGOT) and ALT (SGPT) ≤ 3 x UNL(upper limit of normal)
  • Serum bilirubin ≤ 1.5 x ULN (but, Gilbert syndrome ≤ 3 x UNL)
  • Serum Cr ≤ 1.5 x UNL

• 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 FLC level ≥ 100mg/L(≥10mg/dL)
• more than 24 weeks prior to last bortezomib dose
• must have signed the consent form

Exclusion Criteria:

• Patients with central neurological 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 active hepatitis, HIV positive(exception, non active hepatitis)
• peripheral neuropathy ≥ CTCAE grade 2 or peripheral neuropathy ≥ CTCAE grade 1 with pain within 2 weeks prior to first dose of study drug
• 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
• 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 bortezomib or dexamethasone
• patients without best overall response is above minimal response based on IMWG 2015 past all treatment for multiple myeloma
• patients with refractory to past bortezomib treatment(ex; under minimal response) or progress within 60days prior to last bortezomib treatment

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) Bortezomib Dexamethasone	Drug: CKD-581; Intravenously on Days 1, 8 of each 21-day treatment cycle.; Other Names: CKD-581 bortezomib dexamethasone regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Tolerated Dose(MTD)	Up to 21 days(for 1st cycle)

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics(Cmax)	1st Cycle day1, Day8: up to 24hr
Number of participants with toxicity as assessed by CTCAE v4.03 through study completion, an average of 1 year	through study completion, an average of 1 year
Objective Response Rate(ORR) of participants as assessed by IMWG uniform response criteria(2011) every 6weeks	every 6weeks, up to 1year
Progression Free Survival(PFS) of participants as assessed by IMWG uniform response criteria(2011) every 6weeks	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) of participants as assessed by IMWG uniform response criteria(2011) every 6weeks	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) of participants as assessed by IMWG uniform response criteria(2011) every 6weeks	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)	1st Cycle day1, Day8: up to 24hr
Pharmacokinetics(CL)	1st Cycle day1, Day8: up to 24hr
Pharmacokinetics(AUClast)	1st Cycle day1, Day8: up to 24hr
Pharmacokinetics(AUCinf)	1st Cycle day1, Day8: up to 24hr
Pharmacokinetics(Vd)	1st Cycle day1, Day8: up to 24hr
Pharmacokinetics( MRT)	1st Cycle day1, Day8: up to 24hr

Collaborators and Investigators

• Sponsor: Chong Kun Dang Pharmaceutical
• Investigators: Study Director: Min Ji Song, Chong Kun Dang Pharmaceutical Corp.

Study record dates

Study Major Dates

• Study Start: January 1, 2017
• Primary Completion (Anticipated): April 1, 2021
• Study Completion (Anticipated): November 1, 2022

Study Registration Dates

• First Submitted: January 9, 2017
• First Submitted That Met QC Criteria: February 9, 2017
• First Posted (Actual): February 14, 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; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Histone Deacetylase Inhibitors; Dexamethasone; Bortezomib; CKD-581
• Other Study ID Numbers: 133MM16010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED