Back to resultsStudy of Subcutaneous and Intravenous Velcade in Combination With Dexamethasone in Chinese Subjects With Relapsed and Refractory Multiple Myeloma
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Bortezomib
Dexamethasone
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma
Eligibility Criteria
Inclusion Criteria:
- Have received at least 1 and no more than 3 prior lines of therapy for multiple myeloma
- Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
- The toxicities resulting from previous therapy must be resolved or stabilized to less than or equal (<=)Grade 1 prior to drug administration
- A woman of childbearing potential must have a negative highly sensitive serum (human chorionic gonadotropin [hCG]) or urine pregnancy tests at screening within 14 days prior to Cycle 1 Day 1
- Have documented evidence of progressive disease/disease progression based on investigator's determination of response by the International Myeloma Working Group (IMWG) criteria on or after their last regimen
Exclusion Criteria:
- Received antimyeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the date of randomization. The only exception is emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 milligram per day (mg/day) for a maximum of 4 days) before treatment.
- Received autologous stem cell transplant (ASCT) within 12 weeks before the date of randomization, or the participant has previously received an allogenic stem cell transplant (regardless of timing)
- Plans to undergo a stem cell transplant prior to progression of disease on this study, that is, these participants should not be enrolled in order to reduce disease burden prior to transplant
- Is known to be infected with human immunodeficiency virus (HIV) or active infection with hepatitis B or hepatitis C
- Had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or clinically significant conduction system abnormalities
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Group 1 : Intravenous Bortezomib plus Dexamethasone
Group 2 : Subcutaneous Bortezomib plus Dexamethasone
Arm Description
Participants will receive a 1.3 milligram per square meter per dose (mg/m^2) bortezomib intravenously on Days 1, 4, 8, and 11 of a 3 week cycle. Participants will receive Dexamethasone at a dose of 20 mg oral (PO) on the day of and the day after bortezomib dosing (Days 1, 2, 4, 5, 8, 9, 11, and 12 of each cycle).
Participants will receive a 1.3 milligram per square meter per dose (mg/m^2) bortezomib subcutaneously on Days 1, 4, 8, and 11 of a 3 week cycle. Participants will receive Dexamethasone at a dose of 20 mg oral (PO) on the day of and the day after bortezomib dosing (Days 1, 2, 4, 5, 8, 9, 11, and 12 of each cycle).
Outcomes
Primary Outcome Measures
Overall Response Rate After 4 Cycles of Velcade Treatment
ORR defined as the proportion of participants who achieve either complete response [CR], very good partial response [VGPR], or partial response [PR], according to the International Myeloma Working Group (IMWG) criteria. Participants with CR, VGPR, or PR that is unconfirmed in Cycle 4 but confirmed in the next response assessment will be included as CR, VGPR or PR, respectively.
Secondary Outcome Measures
Complete Response (CR) and Very Good Partial Response (VGPR) after 4 cycles
CR and VGPR defined as the proportion of participants who achieve either complete response [CR] or very good partial response [VGPR], according to the IMWG criteria, after 4 cycles of Velcade treatment. Participants with CR or VGPR that is unconfirmed in Cycle 4 but further confirmed in the next response assessment will be included.
Overall Response Rate (ORR) after 8 cycles
ORR is defined as the proportion of participants who achieve either CR, VGPR, or PR according to the IMWG criteria, after 8 cycles of Vd treatment. Participants with CR, VGPR or PR that is unconfirmed in Cycle 8 but further confirmed in the next response assessment will be included.
Progression-Free Survival (PFS)
PFS is defined as the time from the date of randomization to the date of first documented progressive disease/disease progression (PD), or death due to any cause, whichever occurs earlier. Participants who have not progressed and are alive on the cut-off date for analysis will be censored at the date of the last clinical assessment of response.
One-year survival rate
One-year survival rate is defined as survival rate at 1 year after randomization. If a participant is alive or the vital status is unknown, then data will be censored at the date that the participant is last known to be alive.
Time to response
Time to response is defined as the time from the date of randomization to the date of the first documentation of a confirmed CR, VGPR, or PR. Participants without response (CR/VGPR/PR) will be censored either at PD or at the last clinical assessment of response.
Time to progression (TTP)
Time to progression is defined as the time from the date of randomization to the date of first documentation of PD. Participants who have not progressed will be censored at the date of the last clinical assessment of response.
Duration of response (DOR)
Duration of response is defined as the time from the date of first documentation of a confirmed CR, VGPR, or PR (overall cycles) to the date of first documented PD. Responders without PD will be censored at the date of the last clinical assessment of response.
Time to best response
Time to best response is defined as the time from the date of randomization to the date of the first evaluation of the overall best response (CR/VGPR/PR) to treatment. Participants without response (CR/VGPR/PR) will be censored either at PD or at the last clinical assessment of response.
Maximum Observed Plasma Concentration (Cmax)
Drug concentration vs. time profile following the 4th dose in Cycle 1 and derived Pharmacokinetic (PK) parameter Cmax will be assessed. Cmax is the observed maximum plasma concentration, taken directly from the plasma concentration-time profile.
Area Under the Plasma ConcentrationTime Curve From Time 0 to Last Observed Quantifiable Concentration AUC [0-last]
Drug concentration vs. time profile following the 4th dose in Cycle 1 and derived Pharmacokinetic (PK) parameter AUC [0-last] will be assessed. AUC [0-last] is the area under the plasma-concentration versus time curve from time 0 to the time of last quantifiable time point, calculated by linear trapezoidal summation.
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Drug concentration vs. time profile following the 4th dose in Cycle 1 and derived Pharmacokinetic (PK) parameter Tmax will be assessed. Tmax is the time when Cmax is observed, taken directly from the plasma concentration-time profile.
Number of Participants with Treatment-Related Adverse Events and Serious Treatment-Related Adverse Events
Number of Participants with adverse events will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0.3 and also vital signs, clinical laboratory tests, local injection site tolerability, and electrocardiograms (ECGs) will be assessed.
Full Information
NCT ID
NCT02811978
First Posted
May 26, 2016
Last Updated
November 7, 2019
Sponsor
Janssen Research & Development, LLC
1. Study Identification
Unique Protocol Identification Number
NCT02811978
Brief Title
Study of Subcutaneous and Intravenous Velcade in Combination With Dexamethasone in Chinese Subjects With Relapsed and Refractory Multiple Myeloma
Official Title
A Phase 3, Randomized, Open-label Study of Subcutaneous and Intravenous VELCADE in Combination With Dexamethasone in Chinese Subjects With Relapsed or Refractory Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
September 27, 2016 (Actual)
Primary Completion Date
May 7, 2018 (Actual)
Study Completion Date
November 10, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
4. Oversight
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this phase 3 study is to determine if subcutaneous velcade is non-inferior to intravenous velcade when administered in combination with low-dose dexamethasone in chinese refractory or relapsed multiple myeloma (r/rMM) patients. The study will assess the overall response rate after 4 cycles of velcade and dexamethasone administration.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
81 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1 : Intravenous Bortezomib plus Dexamethasone
Arm Type
Experimental
Arm Description
Participants will receive a 1.3 milligram per square meter per dose (mg/m^2) bortezomib intravenously on Days 1, 4, 8, and 11 of a 3 week cycle. Participants will receive Dexamethasone at a dose of 20 mg oral (PO) on the day of and the day after bortezomib dosing (Days 1, 2, 4, 5, 8, 9, 11, and 12 of each cycle).
Arm Title
Group 2 : Subcutaneous Bortezomib plus Dexamethasone
Arm Type
Experimental
Arm Description
Participants will receive a 1.3 milligram per square meter per dose (mg/m^2) bortezomib subcutaneously on Days 1, 4, 8, and 11 of a 3 week cycle. Participants will receive Dexamethasone at a dose of 20 mg oral (PO) on the day of and the day after bortezomib dosing (Days 1, 2, 4, 5, 8, 9, 11, and 12 of each cycle).
Intervention Type
Drug
Intervention Name(s)
Bortezomib
Other Intervention Name(s)
Velcade, JNJ-26866138-AAA
Intervention Description
Participants will receive 1.3 mg/m^2 bortezomib on Days 1, 4, 8, and 11 of a 3 week cycle.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Participants will receive Dexamethasone at a dose of 20 mg PO on the day of and the day after bortezomib dosing (Days 1, 2, 4, 5, 8, 9, 11, and 12 of each cycle).
Primary Outcome Measure Information:
Title
Overall Response Rate After 4 Cycles of Velcade Treatment
Description
ORR defined as the proportion of participants who achieve either complete response [CR], very good partial response [VGPR], or partial response [PR], according to the International Myeloma Working Group (IMWG) criteria. Participants with CR, VGPR, or PR that is unconfirmed in Cycle 4 but confirmed in the next response assessment will be included as CR, VGPR or PR, respectively.
Time Frame
12 weeks (after 4 cycles; each cycle is of 3 weeks)
Secondary Outcome Measure Information:
Title
Complete Response (CR) and Very Good Partial Response (VGPR) after 4 cycles
Description
CR and VGPR defined as the proportion of participants who achieve either complete response [CR] or very good partial response [VGPR], according to the IMWG criteria, after 4 cycles of Velcade treatment. Participants with CR or VGPR that is unconfirmed in Cycle 4 but further confirmed in the next response assessment will be included.
Time Frame
12 weeks (after 4 cycles; each cycle is of 3 weeks)
Title
Overall Response Rate (ORR) after 8 cycles
Description
ORR is defined as the proportion of participants who achieve either CR, VGPR, or PR according to the IMWG criteria, after 8 cycles of Vd treatment. Participants with CR, VGPR or PR that is unconfirmed in Cycle 8 but further confirmed in the next response assessment will be included.
Time Frame
24 weeks (after 8 cycle; each cycle is of 3 weeks)
Title
Progression-Free Survival (PFS)
Description
PFS is defined as the time from the date of randomization to the date of first documented progressive disease/disease progression (PD), or death due to any cause, whichever occurs earlier. Participants who have not progressed and are alive on the cut-off date for analysis will be censored at the date of the last clinical assessment of response.
Time Frame
Maximum up to 4 years 7 months
Title
One-year survival rate
Description
One-year survival rate is defined as survival rate at 1 year after randomization. If a participant is alive or the vital status is unknown, then data will be censored at the date that the participant is last known to be alive.
Time Frame
1 year after last patient randomization
Title
Time to response
Description
Time to response is defined as the time from the date of randomization to the date of the first documentation of a confirmed CR, VGPR, or PR. Participants without response (CR/VGPR/PR) will be censored either at PD or at the last clinical assessment of response.
Time Frame
Maximum up to 4 years 7 months
Title
Time to progression (TTP)
Description
Time to progression is defined as the time from the date of randomization to the date of first documentation of PD. Participants who have not progressed will be censored at the date of the last clinical assessment of response.
Time Frame
Maximum up to 4 years 7 months
Title
Duration of response (DOR)
Description
Duration of response is defined as the time from the date of first documentation of a confirmed CR, VGPR, or PR (overall cycles) to the date of first documented PD. Responders without PD will be censored at the date of the last clinical assessment of response.
Time Frame
Maximum up to 4 years 7 months
Title
Time to best response
Description
Time to best response is defined as the time from the date of randomization to the date of the first evaluation of the overall best response (CR/VGPR/PR) to treatment. Participants without response (CR/VGPR/PR) will be censored either at PD or at the last clinical assessment of response.
Time Frame
Maximum up to 4 years 7 months
Title
Maximum Observed Plasma Concentration (Cmax)
Description
Drug concentration vs. time profile following the 4th dose in Cycle 1 and derived Pharmacokinetic (PK) parameter Cmax will be assessed. Cmax is the observed maximum plasma concentration, taken directly from the plasma concentration-time profile.
Time Frame
Cycle 1 of Day 1, Day 11 to Day 14
Title
Area Under the Plasma ConcentrationTime Curve From Time 0 to Last Observed Quantifiable Concentration AUC [0-last]
Description
Drug concentration vs. time profile following the 4th dose in Cycle 1 and derived Pharmacokinetic (PK) parameter AUC [0-last] will be assessed. AUC [0-last] is the area under the plasma-concentration versus time curve from time 0 to the time of last quantifiable time point, calculated by linear trapezoidal summation.
Time Frame
Cycle 1 of Day 1, Day 11 to Day 14
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Description
Drug concentration vs. time profile following the 4th dose in Cycle 1 and derived Pharmacokinetic (PK) parameter Tmax will be assessed. Tmax is the time when Cmax is observed, taken directly from the plasma concentration-time profile.
Time Frame
Cycle 1 of Day 1, Day 11 to Day 14
Title
Number of Participants with Treatment-Related Adverse Events and Serious Treatment-Related Adverse Events
Description
Number of Participants with adverse events will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0.3 and also vital signs, clinical laboratory tests, local injection site tolerability, and electrocardiograms (ECGs) will be assessed.
Time Frame
Maximum up to 4 years 7 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Have received at least 1 and no more than 3 prior lines of therapy for multiple myeloma
Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
The toxicities resulting from previous therapy must be resolved or stabilized to less than or equal (<=)Grade 1 prior to drug administration
A woman of childbearing potential must have a negative highly sensitive serum (human chorionic gonadotropin [hCG]) or urine pregnancy tests at screening within 14 days prior to Cycle 1 Day 1
Have documented evidence of progressive disease/disease progression based on investigator's determination of response by the International Myeloma Working Group (IMWG) criteria on or after their last regimen
Exclusion Criteria:
Received antimyeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the date of randomization. The only exception is emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 milligram per day (mg/day) for a maximum of 4 days) before treatment.
Received autologous stem cell transplant (ASCT) within 12 weeks before the date of randomization, or the participant has previously received an allogenic stem cell transplant (regardless of timing)
Plans to undergo a stem cell transplant prior to progression of disease on this study, that is, these participants should not be enrolled in order to reduce disease burden prior to transplant
Is known to be infected with human immunodeficiency virus (HIV) or active infection with hepatitis B or hepatitis C
Had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or clinically significant conduction system abnormalities
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
City
Beijing
Country
China
City
Chengdu
Country
China
City
Chongqing
Country
China
City
Fuzhou
Country
China
City
Guangzhou
Country
China
City
Nanjing
Country
China
City
Shanghai
Country
China
City
Suzhou
Country
China
City
Tianjin
Country
China
City
Wuhan
Country
China
12. IPD Sharing Statement
Links:
URL
https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217051&parentIdentifier=CR108175&attachmentIdentifier=77e89ae3-7f6b-4eb6-8499-925c2be8f4d6&fileName=CR108175_CSR_Synopsis.pdf&versionIdentifier=
Description
A Phase 3, Randomized, Open-label Study of Subcutaneous and Intravenous VELCADE® in Combination with Dexamethasone in Chinese Subjects with Relapsed or Refractory Multiple Myeloma
Learn more about this trial
Study of Subcutaneous and Intravenous Velcade in Combination With Dexamethasone in Chinese Subjects With Relapsed and Refractory Multiple Myeloma
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