Myeloma, Multiple
Conditions
Brief summary
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.
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.
Interventions
DRUGTreat 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
Sponsors
Chong Kun Dang Pharmaceutical
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MTD | Up to 28 days(for 1st cycle) | Maximum Tolerated Dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics(Cmax) | 1st Cycle day1: up to 24hr | Pharmacokinetics |
Other
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival(OS) | Average time period between the start day of induction therapy and the day of death, due to any cause, up to 1year | Overall Survival(OS) of participants as assessed by IMWG uniform response criteria(2011) every 4weeks |
| Duration of Response(DOR) | Average time period between the day of first achievement of response and the day of first relapse or progression, up to 1year | Duration of Response(DOR) of participants as assessed by IMWG uniform response criteria(2011) every 4weeks |
| Pharmacokinetics(T1/2) | 1st Cycle day1: up to 24hr | Pharmacokinetics |
| Pharmacokinetics(CL) | 1st Cycle day1: up to 24hr | Pharmacokinetics |
| Objective Response Rate(ORR) | 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 | Objective Response Rate(ORR) of participants as assessed by IMWG uniform response criteria(2011) every 4weeks |
| Pharmacokinetics(AUCinf) | 1st Cycle day1: up to 24hr | Pharmacokinetics |
| Pharmacokinetics(Vd) | 1st Cycle day1: up to 24hr | Pharmacokinetics |
| Pharmacokinetics( MRT) | 1st Cycle day1: up to 24hr | Pharmacokinetics |
| Adverse events | through study completion, an average of 1 year | Adverse events will be assessed using CTCAE criteria. |
| Pharmacokinetics(AUClast) | 1st Cycle day1: up to 24hr | Pharmacokinetics |
| Progression Free Survival(PFS) | 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) of participants as assessed by IMWG uniform response criteria(2011) every 4weeks |
Countries
South Korea
Contacts
Primary ContactMinji Song
Outcome results
None listed