A Pharmacokinetic Study of Bortezomib in Taiwanese Participants With Multiple Myeloma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the pharmacokinetic (PK-the study of the way a drug enters and leaves the blood and tissues over time) characteristics of bortezomib when administered intravenously in Taiwanese participants with multiple myeloma (cancer of the types of cells normally found in bone marrow).

Detailed Description
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This is a Phase 4, single-arm, open-label (all knew the intervention of study), and multicenter (when more than 1 hospital or medical school team work on a medical research study) study to explore the pharmacokinetics with relapsed (the return of a medical problem) or refractory (not responding to treatment) multiple myeloma. The study consists of a Screening phase and a bortezomib treatment phase with defined PK sample collection time points. Participants will receive bortezomib intravenous injection two times a week up to 2 weeks (on Days 1, 4, 8, and 11) and followed by a 10-day resting phase (Days 12 to 21) for 1 treatment cycle. Pharmacokinetics will primarily be evaluated. Participants' safety will be monitored throughout the study.

Official Title
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Pharmacokinetic Study of Bortezomib (VELCADE) Administered Intravenously in Taiwanese Patients With Multiple Myeloma - A Post Approval Commitment Study

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Bortezomib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of multiple myeloma based on the standard criteria Measurable, secretory multiple myeloma is defined as serum monoclonal immunoglobulin (Ig) G of >= 10 gram per liters (g/L), serum monoclonal IgA or IgE greater than or equal to (>=) 5 g/L, serum monoclonal IgD >= 0.5 g/L, or serum monoclonal IgM present (regardless of level), or urine M protein of >= 200 mg/24 hour at any time point of prior treatment Relapse or progression of myeloma following prior systemic antineoplastic therapy and meet the indication which had been approved in the drug leaflet. Relapse is defined as: a) reappearance of measurable disease (as defined above) following complete response (CR); b) >= 25 percent (%) increase in serum or urine M-protein according to IMWG (International Myeloma Working group) criteria; c) development of new or worsening lytic bone disease; d) new plasmacytomas or >=50% increase in the longest dimension of an existing plasmacytoma; e) worsening hypercalcemia (corrected serum calcium >11.5 milligram per deciliters [mg/dL-2.8 millimoles per liters [mmol/L] due to multiple myeloma Karnofsky performance status >=70% Platelet count >=50 × 10^9 /L without transfusion support within 7 days before the laboratory test Exclusion Criteria: More than 3 previous lines of therapy (separate lines of therapy are defined as single or combination therapies that are either separated by disease progression or by a >6 month treatment-free interval) Peripheral neuropathy or neuropathic pain of National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade >=2 Any of the following within 3 weeks prior to enrollment in the study: antineoplastic or experimental therapy, corticosteroid use above 10 mg/day (prednisone or equivalent), or plasmapheresis Any of the following within 2 weeks prior to enrollment in the study: radiation therapy, major surgery (kyphoplasty is not considered major surgery) Prior malignancy other than multiple myeloma diagnosed or treated within the last 2 years, with the exception of completely resected carcinoma in situ or basal/squamous carcinoma of the skin

Ages Eligible for Study
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Minimum Age: 20 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: Bortezomib<br>Participants will receive a 1.3 milligram per square meter per dose (mg/m^2/dose) of bortezomib intravenously on Days 1, 4, 8, and 11. | Drug: Bortezomib<br>* Participants will receive a 1.3 milligram per square meter per dose (mg/m^2/dose) of bortezomib intravenously on Days 1, 4, 8, and 11.<br>* Other names: Velcade;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Initial Observed Plasma Drug Concentration (Co) | Initial concentration extrapolated to time zero (Co) will be evaluated. | 72 hours pre-dose on Day 1 (Baseline); post-dose on Day 11, 12, 13 and 14 | 
| Maximum Observed Plasma Concentration (Cmax) | Maximum observed plasma concentration (Cmax) will be observed. | 72 hours pre-dose on Day 1 (Baseline); post-dose on Day 11, 12, 13 and 14 | 
| Area Under Plasma Concentration-Time Curve From Time 0 to Last Quantifiable Time Point | Area under the plasma concentration-time curve from time 0 to the time of last quantifiable time point, calculated by linear trapezoidal summation. | 72 hours pre-dose on Day 1 (Baseline); post-dose on Day 11, 12, 13 and 14 | 
| Area Under Plasma Concentration-Time Curve From Time 0 to Infinity (AUC-Infinity) | Area under the plasma concentration-time curve from time 0 to infinity, calculated as AUClast + Clast/lamda(z), where Clast is the last measurable plasma concentration and lamda(z) is the terminal rate constant. | 72 hours pre-dose on Day 1 (Baseline); post-dose on Day 11, 12, 13 and 14 | 
| Terminal Half-life (t1/2) | Terminal half-life, calculated by 0.693/lamda(z). | 72 hours pre-dose on Day 1 (Baseline); post-dose on Day 11, 12, 13 and 14 | 
| Terminal rate constant (lamda[z]) | Terminal rate constant estimated by log-linear regression analysis of the terminal phase of the plasma concentration versus time curve for at least 3 points. | 72 hours pre-dose on Day 1 (Baseline); post-dose on Day 11, 12, 13 and 14 | 
| Systemic clearance (CL) | Systemic clearance after IV dose, estimated by dividing the total administered dose by the plasma (AUC-Infinity). | 72 hours pre-dose on Day 1 (Baseline); post-dose on Day 11, 12, 13 and 14 | 
| Apparent Volume of Distribution (Vd) | Apparent volume of distribution (Vd) based on the terminal phase after intravenous administration, calculated as Dose/(Lamda[z] * AUC-Infinity). | 72 hours pre-dose on Day 1 (Baseline); post-dose on Day 11, 12, 13 and 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Velcade, Multiple Myeloma, Bortezomib