A Post-Approval Pharmacokinetic Study of Bortezomib in Participants With Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title:

A Post Approval Commitment Study for Pharmacokinetic Analysis and Providing Expanded Access to Bortezomib (Velcade) for Patients With Multiple Myeloma Who Have Received at Least Two Previous Lines of Therapy and Are Refractory to or Have Relapsed After Their Last Therapy for Multiple Myeloma in Taiwan

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01801436
• Other study ID #: CR013843
• Secondary ID: 26866138MMY3014
• Status: Completed
• Phase: Phase 3
• First received: February 27, 2013
• Last updated: March 28, 2013
• Start date: December 2006
• Est. completion date: April 2008

Study information

• Verified date: March 2013
• Source: Johnson & Johnson Taiwan Ltd
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this post marketing study is to determine the plasma concentration of bortezomib (unchanged drug) to assess the pharmacokinetic (PK - the study of the way a drug enters and leaves the blood and tissues over time) properties in the Taiwanese population. It will also provide expanded access (expanded access, sometimes called "compassionate use," is the use of an investigational drug outside of a clinical trial to treat a participant with a serious or immediately life-threatening disease or condition who has no comparable or satisfactory alternative treatment options) to bortezomib for the same group of participants with multiple myeloma (cancer of the types of cells normally found in bone marrow).

Description:

This is an open-label (all people know the identity of the intervention), single-arm, multi-center (conducted in more than 1 center) study to assess the PK of bortezomib and to provide expanded access to bortezomib for 14 Taiwanese participants with multiple myeloma who have received at least 2 previous lines of therapy (medicine or medical care given to a participant for a disease or condition) and are refractory (not responding to treatment) to or have relapsed (the return of a medical problem) after their last therapy. Eligible participants will receive bortezomib 1.3 milligram (mg) per meter square (m^2) on Days 1, 4, 8, and 11 of each 3-week cycle for up to 8 cycles. Blood samples for PK assessment will be collected on specified time points of Day 1, Day 8, and Day 11 of Cycle 1. Efficacy of the participants will primarily be evaluated by recording 'response to treatment' and 'Karnofsky Performance Status'. Participants' safety will be monitored throughout the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: April 2008
• Est. primary completion date: April 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Participants previously diagnosed with multiple myeloma based on standard criteria

• Participant has received at least 2 previous lines of therapy for multiple myeloma and, in the Investigator's opinion, currently requires therapy because of relapsed (the return of a medical problem) or progressive disease

• Female participants either postmenopausal or surgically sterilized or willing to use an acceptable method of birth control from Screening through the Final Visit

• If male, the participant agrees to use an acceptable barrier method for contraception from Screening through the Final Visit

• Participant has a Karnofsky performance status classifies participants as to their functional impairment and is used to compare effectiveness of different therapies and to assess the prognosis [outlook, probable outcomes] in individual participants) greater than 60

Exclusion Criteria:

• If the participant received bortezomib in a previous trial, the Participants' best response to bortezomib must be progressive disease

• If the participant received bortezomib in a previous trial, the participant must have experienced 1 or more serious adverse events

• Participants who have received nitrosoureas within 6 weeks or any other chemotherapy (treatment of disease, usually cancer, by chemical agents) within 3 weeks before enrollment

• Participants who have received corticosteroids (greater than 10 milligram per day prednisone or equivalent) within 3 weeks before enrollment

• Human Immunodeficiency Virus (HIV - a life-threatening infection which you can get from an infected person's blood or from having sex with an infected person)-positive or hepatitis-B surface antigen-positive participants or participants with known active hepatitis-C infection

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Bortezomib
Bortezomib 1.3 mg per (m^2) on Days 1, 4, 8, and 11 of each 3-week cycle for up to 8 cycles.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Johnson & Johnson Taiwan Ltd

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Response to Treatment at Day 1 of Cycle 5	Response to treatment was based on the changes in monoclonal protein (M-protein) in serum and urine. Response categories were complete response: complete clearance of M-protein for at least 6 weeks, response: at least 75 percent reduction in M-protein for at least 2 determinations 6 weeks apart, partial response: 50 to 74 percent reduction in M-protein, minimal response: 25 to 49 percent reduction in M-protein, stable disease: not qualifying minimal response or progression and progression: increased M-protein level in serum or urine or clinical signs of disease progression.	Day 1 of Cycle 5	No
Primary	Number of Participants With Response to Treatment at Day 1 of Cycle 7	Response to treatment was based on the changes in monoclonal protein (M-protein) in serum and urine. Response categories were complete response: complete clearance of M-protein for at least 6 weeks, response: at least 75 percent reduction in M-protein for at least 2 determinations 6 weeks apart, partial response: 50 to 74 percent reduction in M-protein, minimal response: 25 to 49 percent reduction in M-protein, stable disease: not qualifying minimal response or progression and progression: increased M-protein level in serum or urine or clinical signs of disease progression.	Day 1 of Cycle 7	No
Primary	Number of Participants With Response to Treatment at Day 11 of Cycle 8	Response to treatment was based on the changes in monoclonal protein (M-protein) in serum and urine. Response categories were complete response: complete clearance of M-protein for at least 6 weeks, response: at least 75 percent reduction in M-protein for at least 2 determinations 6 weeks apart, partial response: 50 to 74 percent reduction in M-protein, minimal response: 25 to 49 percent reduction in M-protein, stable disease: not qualifying minimal response or progression and progression: increased M-protein level in serum or urine or clinical signs of disease progression.	Day 11 of Cycle 8	No
Primary	Number of Participants With Karnofsky Performance Status (KPS) Score at Baseline	The KPS Index allows participants to be classified as per their functional impairment (abnormal function). This can be used to compare effectiveness of different therapies (medicine or medical care given to a participant for a disease or condition) and to assess the prognosis (outlook, probable outcomes) in individual participants. KPS was recorded on an 11-point scale (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100.) where '0=Dead' and '100=Normal, no complaints, no evidence of disease'. The lower the Karnofsky score, the worse the survival for most serious illnesses.	Baseline	No
Primary	Number of Participants With KPS Score at Day 1 of Cycle 1	The KPS Index allows participants to be classified as per their functional impairment (abnormal function). This can be used to compare effectiveness of different therapies (medicine or medical care given to a participant for a disease or condition) and to assess the prognosis (outlook, probable outcomes) in individual participants. KPS was recorded on an 11-point scale (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100.) where '0=Dead' and '100=Normal, no complaints, no evidence of disease'. The lower the Karnofsky score, the worse the survival for most serious illnesses.	Day 1 of Cycle 1	No
Primary	Number of Participants With KPS Score at Day 1 of Cycle 3	The KPS Index allows participants to be classified as per their functional impairment (abnormal function). This can be used to compare effectiveness of different therapies (medicine or medical care given to a participant for a disease or condition) and to assess the prognosis (outlook, probable outcomes) in individual participants. KPS was recorded on an 11-point scale (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100.) where '0=Dead' and '100=Normal, no complaints, no evidence of disease'. The lower the Karnofsky score, the worse the survival for most serious illnesses.	Day 1 of Cycle 3	No
Primary	Number of Participants With KPS Score at Day 1 of Cycle 5	The KPS Index allows participants to be classified as per their functional impairment (abnormal function). This can be used to compare effectiveness of different therapies (medicine or medical care given to a participant for a disease or condition) and to assess the prognosis (outlook, probable outcomes) in individual participants. KPS was recorded on an 11-point scale (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100.) where '0=Dead' and '100=Normal, no complaints, no evidence of disease'. The lower the Karnofsky score, the worse the survival for most serious illnesses.	Day 1 of Cycle 5	No
Primary	Number of Participants With KPS Score at Day 1 of Cycle 7	The KPS Index allows participants to be classified as per their functional impairment (abnormal function). This can be used to compare effectiveness of different therapies (medicine or medical care given to a participant for a disease or condition) and to assess the prognosis (outlook, probable outcomes) in individual participants. KPS was recorded on an 11-point scale (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100.) where '0=Dead' and '100=Normal, no complaints, no evidence of disease'. The lower the Karnofsky score, the worse the survival for most serious illnesses.	Day 1 of Cycle 7	No
Primary	Number of Participants With KPS Score at Day 11 of Cycle 8	The KPS Index allows participants to be classified as per their functional impairment (abnormal function). This can be used to compare effectiveness of different therapies (medicine or medical care given to a participant for a disease or condition) and to assess the prognosis (outlook, probable outcomes) in individual participants. KPS was recorded on an 11-point scale (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100.) where '0=Dead' and '100=Normal, no complaints, no evidence of disease'. The lower the Karnofsky score, the worse the survival for most serious illnesses.	Day 11 of Cycle 8	No
Primary	Maximum Observed Plasma Concentration (Cmax) of Bortezomib on Day 1 of Cycle 1	The Cmax is observed maximum plasma concentration, taken directly from the plasma concentration-time profile.	0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 1 of Cycle 1	No
Primary	Maximum Observed Plasma Concentration (Cmax) of Bortezomib on Day 11 of Cycle 1	The Cmax is observed maximum plasma concentration, taken directly from the plasma concentration-time profile.	0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1	No
Primary	Time to Reach Maximum Observed Plasma Concentration (Tmax) of Bortezomib on Day 1 of Cycle 1	Tmax is the time when Cmax is observed, taken directly from the plasma concentration-time profile.	0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 1 of Cycle 1	No
Primary	Time to Reach Maximum Observed Plasma Concentration (Tmax) of Bortezomib on Day 11 of Cycle 1	Tmax is the time when Cmax is observed, taken directly from the plasma concentration-time profile.	0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1	No
Primary	Elimination Half-Life Period (T1/2) of Bortezomib on Day 1 of Cycle 1	The T1/2 is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal rate-constant (lambda[z]) of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).	0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 1 of Cycle 1	No
Primary	Elimination Half-Life Period (T1/2) of Bortezomib on Day 11 of Cycle 1	The T1/2 is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal rate-constant (lambda[z]) of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).	0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1	No
Primary	Terminal Rate Constant (Lambda[z]) of Bortezomib on Day 1 of Cycle 1	Lambda(z) is defined as terminal rate-constant which reflect the speed of drug elimination in vivo (within the living), and is estimated by log-linear regression analysis of the terminal phase of the plasma concentration versus time curve for at least 3 points.	0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 1 of Cycle 1	No
Primary	Terminal Rate Constant (Lambda[z]) of Bortezomib on Day 11 of Cycle 1	Lambda(z) is defined as terminal rate-constant which reflect the speed of drug elimination in vivo (within the living), and is estimated by log-linear regression analysis of the terminal phase of the plasma concentration versus time curve for at least 3 points.	0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1	No
Primary	Area Under the Plasma Concentration-Time Curve From Time Zero to Time at Last Observed Quantifiable Concentration (AUC[0-t]) of Bortezomib on Day 1 of Cycle 1	The AUC(0-t) is area under the plasma concentration-time curve from time zero to the last quantifiable concentration determined by the trapezoidal rule.	0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 1 of Cycle 1	No
Primary	Area Under the Plasma Concentration-Time Curve From Time Zero to Time at Last Observed Quantifiable Concentration (AUC[0-t]) of Bortezomib on Day 11 of Cycle 1	The AUC(0-t) is area under the plasma concentration-time curve from zero to the last quantifiable concentration determined by the trapezoidal rule.	0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1	No
Primary	Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Bortezomib on Day 1 of Cycle 1	The AUC(0-infinity) is area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z), in which C(last) is the last observed quantifiable concentration.	Day 1 of Cycle 1	No
Primary	Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Bortezomib on Day 11 of Cycle 1	The AUC(0-infinity) is area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z), in which C(last) is the last observed quantifiable concentration.	0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1	No
Primary	Area Under First Moment Plasma Concentration-Time Curve (AUMC) of Bortezomib on Day 1 of Cycle 1	AUMC is defined as the area under first moment plasma concentration-time curve from time of dosing up to definite time t, to infinity, or to the time of last measurable concentration determined by the following equation: AUMC(0 to infinity)=Cntn/k elimination(el) + Cn/k(el^2) summation[(tn - tn^-1) (Cn^-1) (tn^-1)] + Cntn/2 where Cn=last quantifiable concentration, tn=time at which Cn is measured, k=rate constant.	0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 1 of Cycle 1	No
Primary	Area Under First Moment Plasma Concentration-Time Curve (AUMC) of Bortezomib on Day 11 of Cycle 1	AUMC is defined as the area under first moment plasma concentration-time curve from time of dosing up to definite time t, to infinity, or to the time of last measurable concentration determined by the following equation: AUMC(0 to infinity)=Cntn/k elimination(el) + Cn/k(el^2) summation[(tn - tn^-1) (Cn^-1) (tn^-1)] + Cntn/2 where Cn=last quantifiable concentration, tn=time at which Cn is measured, k=rate constant.	0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1	No
Primary	Mean Residence Time (MRT) of Bortezomib in the Body on Day 1 of Cycle 1	The MRT is the average time at which the number of absorbed molecules reside in the body, after single-dose administration, and calculated as AUMC(infinity)/AUC(infinity) where AUMC(infinity) is area under the plasma concentration-time first moment curve from time zero to infinite time and AUC(infinity) is the area under the plasma concentration-time curve from time zero to infinite time.	0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 1 of Cycle 1	No
Primary	Mean Residence Time (MRT) of Bortezomib in the Body on Day 11 of Cycle 1	The MRT is the average time at which the number of absorbed molecules reside in the body, after single-dose administration, and calculated as AUMC(infinity)/AUC(infinity) where AUMC(infinity) is area under the plasma concentration-time first moment curve from time zero to infinite time and AUC(infinity) is the area under the plasma concentration-time curve from time zero to infinite time.	0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1	No
Primary	Systemic Clearance (CL) of Bortezomib on Day 1 of Cycle 1	Systemic CL is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma AUC(0-infinity).	0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 1 of Cycle 1	No
Primary	Systemic Clearance (CL) of Bortezomib on Day 11 of Cycle 1	Systemic CL is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma AUC(0-infinity).	0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1	No
Primary	Volume of Distribution at Steady-State (Vss) of Bortezomib on Day 1 of Cycle 1	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state which is estimated by (D/AUC[0-infinity])*(AUMC[0-infinity])/AUC[0-infinity]) where D is the dose of study drug, AUMC(0-infinity) is the area under the first moment curve extrapolated to infinity and AUC(0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time.	0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 1 of Cycle 1	No
Primary	Volume of Distribution at Steady-State (Vss) of Bortezomib on Day 11 of Cycle 1	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state which is estimated by (D/AUC[0-infinity])*(AUMC[0-infinity])/AUC[0-infinity]) where D is the dose of study drug, AUMC(0-infinity) is the area under the first moment curve extrapolated to infinity and AUC(0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time.	0 hour (Pre-dose) and 0.08, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 hours (post-dose) on Day 11 of Cycle 1	No