Clinical trial NCT03051841: CKD-581 + Bortezomib + Dexamethasone in Patients With Previously Treated Multiple Myeloma
Official title: A Phase I, Open-Label, Multi-Center Study of CKD-581 in Combination With Bortezomib 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: 2017-02-14
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), 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum Tolerated Dose(MTD)
timeFrame: Up to 21 days(for 1st cycle)
Secondary outcomes:
measure: Pharmacokinetics(Cmax)
timeFrame: 1st Cycle day1, Day8: up to 24hr
measure: Number of participants with toxicity as assessed by CTCAE v4.03 through study completion, an average of 1 year
timeFrame: through study completion, an average of 1 year
measure: Objective Response Rate(ORR) of participants as assessed by IMWG uniform response criteria(2011) every 6weeks
timeFrame: every 6weeks, up to 1year
measure: Progression Free Survival(PFS) of participants as assessed by IMWG uniform response criteria(2011) every 6weeks
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) of participants as assessed by IMWG uniform response criteria(2011) every 6weeks
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) of participants as assessed by IMWG uniform response criteria(2011) every 6weeks
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, Day8: up to 24hr
measure: Pharmacokinetics(CL)
timeFrame: 1st Cycle day1, Day8: up to 24hr
measure: Pharmacokinetics(AUClast)
timeFrame: 1st Cycle day1, Day8: up to 24hr
measure: Pharmacokinetics(AUCinf)
timeFrame: 1st Cycle day1, Day8: up to 24hr
measure: Pharmacokinetics(Vd)
timeFrame: 1st Cycle day1, Day8: up to 24hr
measure: Pharmacokinetics( MRT)
timeFrame: 1st Cycle day1, Day8: up to 24hr
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Chong Kun Dang Pharmaceutical Corp.
name: Min Ji Song
role: STUDY_DIRECTOR
References: