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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Myeloma, Multiple

Intervention / Treatment
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* Drug: CKD-581


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treat Regimen<br>CKD-581(investigational Drug) Bortezomib Dexamethasone | Drug: CKD-581<br>* Intravenously on Days 1, 8 of each 21-day treatment cycle.<br>* Other names: CKD-581 bortezomib dexamethasone regimen;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |