Clinical trial NCT03150316: CKD-581 + Lenalidomide + Dexamethasone in Patients With Previously Treated Multiple Myeloma
Official title: A Phase I, Open-Label, Multi-Center Study of CKD-581 in Combination With Lenalidomide and Dexamethasone in Patients With Previously Treated Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Myeloma, Multiple
Lead sponsor: Chong Kun Dang Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2017-05-12
Enrollment: 18
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: MTD
timeFrame: Up to 28 days(for 1st cycle)
Secondary outcomes:
measure: Pharmacokinetics(Cmax)
timeFrame: 1st Cycle day1: up to 24hr
Other outcomes:
measure: Objective Response Rate(ORR)
timeFrame: 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
measure: Progression Free Survival(PFS)
timeFrame: 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
measure: Overall Survival(OS)
timeFrame: Average time period between the start day of induction therapy and the day of death, due to any cause, up to 1year
measure: Duration of Response(DOR)
timeFrame: Average time period between the day of first achievement of response and the day of first relapse or progression, up to 1year
measure: Pharmacokinetics(T1/2)
timeFrame: 1st Cycle day1: up to 24hr
measure: Pharmacokinetics(CL)
timeFrame: 1st Cycle day1: up to 24hr
measure: Pharmacokinetics(AUClast)
timeFrame: 1st Cycle day1: up to 24hr
measure: Pharmacokinetics(AUCinf)
timeFrame: 1st Cycle day1: up to 24hr
measure: Pharmacokinetics(Vd)
timeFrame: 1st Cycle day1: up to 24hr
measure: Pharmacokinetics( MRT)
timeFrame: 1st Cycle day1: up to 24hr
measure: Adverse events
timeFrame: through study completion, an average of 1 year
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Hospital
state: Gangnam-gu
city: Seoul
country: Korea, Republic of
facility: the catholic university of korea, Seoul ST. Mary's Hospital
state: Seocho
Study officials:
affiliation: The Catholic University of Korea
name: Chanki Min
role: PRINCIPAL_INVESTIGATOR
References: