Trial Outcomes & Findings for A Study of Carfilzomib vs Best Supportive Care in Subjects With Relapsed and Refractory Multiple Myeloma (NCT NCT01302392)

Last Updated: 2017-05-02

Results Overview

Time elapsed between the randomization date and the date of death. Participants who were still alive were censored at date when the subject is last known alive or the data cutoff date, whichever occurs earlier.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

315 participants

Primary outcome timeframe

From randomization through the final analysis data cutoff with longest follow-up time of approximately 45 months. Median follow up times were 27.8 months and 29.8 months for Carfilzomib and Best Supportive Care groups, respectively.

Results posted on

2017-05-02

Participant Flow

Subjects were enrolled from 06 Sep 2010 to 21OCT2012. Results are reported as of the data cut-off date of 10 Jul 2014.

Participant milestones

Participant milestones
Measure	Best Supportive Care Best Supportive Care: Corticosteroid (either prednisolone 30 mg orally (PO) every other day, dexamethasone 6 mg PO every other day, or other equivalent corticosteroid). Optional cyclophosphamide 50 mg PO once daily may be given at the Investigator's discretion (maximum of 1400 mg per 28-day cycle).	Carfilzomib Carfilzomib: 20mg/m² IV on Days 1 and 2 of Cycle 1, escalating to 27 mg/m² IV on Days 8,9,15,and 16 of Cycle 1 and continuing on Days 1,2,8,9,15,and 16 of Cycles 2 through Cycle 9. Cycles 10 and beyond will receive 27 mg/m² IV on Days 1,2,15, and 16 (alternatively, the investigator could choose to continue the dosing frequency on the original dosing days \[Days 1, 2, 8, 9, 15, 16\] for individual subjects).
Overall Study STARTED	158	157
Overall Study Treated	153	157
Overall Study COMPLETED	151	156
Overall Study NOT COMPLETED	7	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Best Supportive Care Best Supportive Care: Corticosteroid (either prednisolone 30 mg orally (PO) every other day, dexamethasone 6 mg PO every other day, or other equivalent corticosteroid). Optional cyclophosphamide 50 mg PO once daily may be given at the Investigator's discretion (maximum of 1400 mg per 28-day cycle).	Carfilzomib Carfilzomib: 20mg/m² IV on Days 1 and 2 of Cycle 1, escalating to 27 mg/m² IV on Days 8,9,15,and 16 of Cycle 1 and continuing on Days 1,2,8,9,15,and 16 of Cycles 2 through Cycle 9. Cycles 10 and beyond will receive 27 mg/m² IV on Days 1,2,15, and 16 (alternatively, the investigator could choose to continue the dosing frequency on the original dosing days \[Days 1, 2, 8, 9, 15, 16\] for individual subjects).
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawal by Subject	6	1

Baseline Characteristics

A Study of Carfilzomib vs Best Supportive Care in Subjects With Relapsed and Refractory Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Best Supportive Care n=158 Participants Best Supportive Care: Corticosteroid (either prednisolone 30 mg orally (PO) every other day, dexamethasone 6 mg PO every other day, or other equivalent corticosteroid). Optional cyclophosphamide 50 mg PO once daily may be given at the Investigator's discretion (maximum of 1400 mg per 28-day cycle).	Carfilzomib n=157 Participants Carfilzomib: 20mg/m² IV on Days 1 and 2 of Cycle 1, escalating to 27 mg/m² IV on Days 8,9,15,and 16 of Cycle 1 and continuing on Days 1,2,8,9,15,and 16 of Cycles 2 through Cycle 9. Cycles 10 and beyond will receive 27 mg/m² IV on Days 1,2,15, and 16 (alternatively, the investigator could choose to continue the dosing frequency on the original dosing days \[Days 1, 2, 8, 9, 15, 16\] for individual subjects).	Total n=315 Participants Total of all reporting groups
Age, Continuous	65.5 years STANDARD_DEVIATION 8.02 • n=5 Participants	63.3 years STANDARD_DEVIATION 10.71 • n=7 Participants	64.4 years STANDARD_DEVIATION 9.50 • n=5 Participants
Sex: Female, Male Female	62 Participants n=5 Participants	75 Participants n=7 Participants	137 Participants n=5 Participants
Sex: Female, Male Male	96 Participants n=5 Participants	82 Participants n=7 Participants	178 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized Asian	4 participants n=5 Participants	1 participants n=7 Participants	5 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized White	148 participants n=5 Participants	151 participants n=7 Participants	299 participants n=5 Participants
Race/Ethnicity, Customized Other	5 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants
Region Europe	138 participants n=5 Participants	140 participants n=7 Participants	278 participants n=5 Participants
Region Non-Europe	20 participants n=5 Participants	17 participants n=7 Participants	37 participants n=5 Participants
Number of Prior Regimens to Treat Multiple Myeloma 3	19 participants n=5 Participants	17 participants n=7 Participants	36 participants n=5 Participants
Number of Prior Regimens to Treat Multiple Myeloma 4	35 participants n=5 Participants	34 participants n=7 Participants	69 participants n=5 Participants
Number of Prior Regimens to Treat Multiple Myeloma ≥5	104 participants n=5 Participants	106 participants n=7 Participants	210 participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization through the final analysis data cutoff with longest follow-up time of approximately 45 months. Median follow up times were 27.8 months and 29.8 months for Carfilzomib and Best Supportive Care groups, respectively.

Population: The intent to treat (ITT) analysis set comprised all randomized participants.

Outcome measures

Outcome measures
Measure	Best Supportive Care n=158 Participants Best Supportive Care: Corticosteroid (either prednisolone 30 mg orally (PO) every other day, dexamethasone 6 mg PO every other day, or other equivalent corticosteroid). Optional cyclophosphamide 50 mg PO once daily may be given at the Investigator's discretion (maximum of 1400 mg per 28-day cycle).	Carfilzomib n=157 Participants Carfilzomib: 20mg/m² IV on Days 1 and 2 of Cycle 1, escalating to 27 mg/m² IV on Days 8,9,15,and 16 of Cycle 1 and continuing on Days 1,2,8,9,15,and 16 of Cycles 2 through Cycle 9. Cycles 10 and beyond will receive 27 mg/m² IV on Days 1,2,15, and 16 (alternatively, the investigator could choose to continue the dosing frequency on the original dosing days \[Days 1, 2, 8, 9, 15, 16\] for individual subjects).
Overall Survival	10.0 months Interval 7.7 to 12.0	10.2 months Interval 8.4 to 14.4

SECONDARY outcome

Timeframe: From randomization through the final analysis data cutoff with longest follow-up time of approximately 31 months. Median follow up times were 26.6 months and 23.1 months for Carfilzomib and Best Supportive Care groups, respectively.

Population: The intent to treat (ITT) analysis set comprised all randomized participants.

Kaplan-Meier estimate of median time from randomization to progressive disease (PD) or all-cause death. PD was assessed using International Myeloma Working Group-Uniform Response Criteria (IMWG-URC). 1 or more conditions were required to meet PD: 2 consecutive rising serum or urine M-protein from central lab; documented new bone lesion(s) or soft tissue plasmacytoma(s) or increased size of existing bone lesion(s) or plasmacytoma(s); or confirmed hypercalcemia due solely to plasma cell proliferative disorder (local lab greater than 11.5 mg/dL on 2 separate occasions). Censoring conditions (censoring dates) were: no post-baseline disease assessment (DA) (randomization date); started non-protocol systemic anticancer treatment before PD or death (last DA date before such treatment); died or had PD after more than 1 missed DA (last DA date without PD before the first missed visit); or were alive and without documentation of PD, including lost to follow-up without PD (last DA date).

Outcome measures

Outcome measures
Measure	Best Supportive Care n=158 Participants Best Supportive Care: Corticosteroid (either prednisolone 30 mg orally (PO) every other day, dexamethasone 6 mg PO every other day, or other equivalent corticosteroid). Optional cyclophosphamide 50 mg PO once daily may be given at the Investigator's discretion (maximum of 1400 mg per 28-day cycle).	Carfilzomib n=157 Participants Carfilzomib: 20mg/m² IV on Days 1 and 2 of Cycle 1, escalating to 27 mg/m² IV on Days 8,9,15,and 16 of Cycle 1 and continuing on Days 1,2,8,9,15,and 16 of Cycles 2 through Cycle 9. Cycles 10 and beyond will receive 27 mg/m² IV on Days 1,2,15, and 16 (alternatively, the investigator could choose to continue the dosing frequency on the original dosing days \[Days 1, 2, 8, 9, 15, 16\] for individual subjects).
Progression-free Survival	3.3 months Interval 2.2 to 5.2	3.7 months Interval 2.8 to 4.2

SECONDARY outcome

Population: The intent to treat (ITT) analysis set comprised all randomized participants.

Number of participants who achieved confirmed stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) as their best response. Response was determined using the International Myeloma Working Group - Uniform Response Criteria (IMWG-URC).

Outcome measures

Outcome measures
Measure	Best Supportive Care n=158 Participants Best Supportive Care: Corticosteroid (either prednisolone 30 mg orally (PO) every other day, dexamethasone 6 mg PO every other day, or other equivalent corticosteroid). Optional cyclophosphamide 50 mg PO once daily may be given at the Investigator's discretion (maximum of 1400 mg per 28-day cycle).	Carfilzomib n=157 Participants Carfilzomib: 20mg/m² IV on Days 1 and 2 of Cycle 1, escalating to 27 mg/m² IV on Days 8,9,15,and 16 of Cycle 1 and continuing on Days 1,2,8,9,15,and 16 of Cycles 2 through Cycle 9. Cycles 10 and beyond will receive 27 mg/m² IV on Days 1,2,15, and 16 (alternatively, the investigator could choose to continue the dosing frequency on the original dosing days \[Days 1, 2, 8, 9, 15, 16\] for individual subjects).
Overall Response	18 participants	30 participants

SECONDARY outcome

Timeframe: From the time achieving response through the final analysis data cutoff with longest follow-up time of approximately 29 months.

Population: The intent to treat (ITT) population comprised randomized participants who achieved a best overall response of PR or better only.

Duration of response (DOR) was calculated for subjects who achieved a best response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR). Duration of response was defined as the time in months from the initial start of response (PR or better) to the earlier of documented progressive disease (PD) or death due to any cause. Participants who had not progressed or died were censored according to the censoring rules defined previously for progression-free survival.

Outcome measures

Outcome measures
Measure	Best Supportive Care n=18 Participants Best Supportive Care: Corticosteroid (either prednisolone 30 mg orally (PO) every other day, dexamethasone 6 mg PO every other day, or other equivalent corticosteroid). Optional cyclophosphamide 50 mg PO once daily may be given at the Investigator's discretion (maximum of 1400 mg per 28-day cycle).	Carfilzomib n=30 Participants Carfilzomib: 20mg/m² IV on Days 1 and 2 of Cycle 1, escalating to 27 mg/m² IV on Days 8,9,15,and 16 of Cycle 1 and continuing on Days 1,2,8,9,15,and 16 of Cycles 2 through Cycle 9. Cycles 10 and beyond will receive 27 mg/m² IV on Days 1,2,15, and 16 (alternatively, the investigator could choose to continue the dosing frequency on the original dosing days \[Days 1, 2, 8, 9, 15, 16\] for individual subjects).
Duration of Response	9.5 months Interval 3.7 to Upper limit of the confidence interval not calculable due to a low number of participants reaching PD or all-cause death.	7.2 months Interval 4.6 to 12.0

SECONDARY outcome

Population: The intent to treat (ITT) analysis set comprised all randomized participants.

Number of participants who achieved confirmed stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), or minimal response (MR) as their best response. Response was determined using the International Myeloma Working Group - Uniform Response Criteria (IMWG-URC). (MR was determined using European Group for Blood and Marrow Transplantation criteria)

Outcome measures

Outcome measures
Measure	Best Supportive Care n=158 Participants Best Supportive Care: Corticosteroid (either prednisolone 30 mg orally (PO) every other day, dexamethasone 6 mg PO every other day, or other equivalent corticosteroid). Optional cyclophosphamide 50 mg PO once daily may be given at the Investigator's discretion (maximum of 1400 mg per 28-day cycle).	Carfilzomib n=157 Participants Carfilzomib: 20mg/m² IV on Days 1 and 2 of Cycle 1, escalating to 27 mg/m² IV on Days 8,9,15,and 16 of Cycle 1 and continuing on Days 1,2,8,9,15,and 16 of Cycles 2 through Cycle 9. Cycles 10 and beyond will receive 27 mg/m² IV on Days 1,2,15, and 16 (alternatively, the investigator could choose to continue the dosing frequency on the original dosing days \[Days 1, 2, 8, 9, 15, 16\] for individual subjects).
Clinical Benefit Response	33 participants	49 participants

SECONDARY outcome

Timeframe: From time of achieving clinical benefit through the final analysis data cutoff with longest follow-up time of approximately 30 months.

Population: The intent to treat (ITT) population comprised randomized participants who achieved a best overall response of MR or better only.

Duration of Clinical Benefit was calculated for subjects who achieved a best response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR) or minimal response (MR). Duration of Clinical Benefit was defined as the time in months from the initial start of response (MR or better) to the earlier of documented progressive disease (PD) or death due to any cause. Participants who had not progressed or died were censored according to the censoring rules defined previously for progression-free survival.

Outcome measures

Outcome measures
Measure	Best Supportive Care n=33 Participants Best Supportive Care: Corticosteroid (either prednisolone 30 mg orally (PO) every other day, dexamethasone 6 mg PO every other day, or other equivalent corticosteroid). Optional cyclophosphamide 50 mg PO once daily may be given at the Investigator's discretion (maximum of 1400 mg per 28-day cycle).	Carfilzomib n=49 Participants Carfilzomib: 20mg/m² IV on Days 1 and 2 of Cycle 1, escalating to 27 mg/m² IV on Days 8,9,15,and 16 of Cycle 1 and continuing on Days 1,2,8,9,15,and 16 of Cycles 2 through Cycle 9. Cycles 10 and beyond will receive 27 mg/m² IV on Days 1,2,15, and 16 (alternatively, the investigator could choose to continue the dosing frequency on the original dosing days \[Days 1, 2, 8, 9, 15, 16\] for individual subjects).
Duration of Clinical Benefit	8.3 months Interval 6.5 to 12.9	6.4 months Interval 4.9 to 8.3

SECONDARY outcome

Population: The intent to treat (ITT) analysis set comprised all randomized participants.

Number of participants who achieved confirmed stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), minimal response (MR), or stable disease (SD) lasting ≥ 8 weeks as their best response. Response was determined using the International Myeloma Working Group - Uniform Response Criteria (IMWG-URC). (MR was determined using European Group for Blood and Marrow Transplantation criteria)

Outcome measures

Outcome measures
Measure	Best Supportive Care n=158 Participants Best Supportive Care: Corticosteroid (either prednisolone 30 mg orally (PO) every other day, dexamethasone 6 mg PO every other day, or other equivalent corticosteroid). Optional cyclophosphamide 50 mg PO once daily may be given at the Investigator's discretion (maximum of 1400 mg per 28-day cycle).	Carfilzomib n=157 Participants Carfilzomib: 20mg/m² IV on Days 1 and 2 of Cycle 1, escalating to 27 mg/m² IV on Days 8,9,15,and 16 of Cycle 1 and continuing on Days 1,2,8,9,15,and 16 of Cycles 2 through Cycle 9. Cycles 10 and beyond will receive 27 mg/m² IV on Days 1,2,15, and 16 (alternatively, the investigator could choose to continue the dosing frequency on the original dosing days \[Days 1, 2, 8, 9, 15, 16\] for individual subjects).
Disease Control	107 participants	119 participants

SECONDARY outcome

Timeframe: From time of achieving disease control through the final analysis data cutoff with longest follow-up time of approximately 31 months.

Population: The intent to treat (ITT) population comprised randomized participants who achieved disease control.

Duration of Disease Control was calculated for subjects who achieved disease control. Duration of Disease Control was defined as the time in months from randomization to the earlier of documented progressive disease (PD) or death due to any cause. Participants who had not progressed or died were censored according to the censoring rules defined previously for progression-free survival.

Outcome measures

Outcome measures
Measure	Best Supportive Care n=107 Participants Best Supportive Care: Corticosteroid (either prednisolone 30 mg orally (PO) every other day, dexamethasone 6 mg PO every other day, or other equivalent corticosteroid). Optional cyclophosphamide 50 mg PO once daily may be given at the Investigator's discretion (maximum of 1400 mg per 28-day cycle).	Carfilzomib n=119 Participants Carfilzomib: 20mg/m² IV on Days 1 and 2 of Cycle 1, escalating to 27 mg/m² IV on Days 8,9,15,and 16 of Cycle 1 and continuing on Days 1,2,8,9,15,and 16 of Cycles 2 through Cycle 9. Cycles 10 and beyond will receive 27 mg/m² IV on Days 1,2,15, and 16 (alternatively, the investigator could choose to continue the dosing frequency on the original dosing days \[Days 1, 2, 8, 9, 15, 16\] for individual subjects).
Duration of Disease Control	6.6 months Interval 5.4 to 8.8	5.5 months Interval 3.9 to 6.5

Adverse Events

Best Supportive Care

Serious events: 78 serious events

Other events: 135 other events

Deaths: 0 deaths

Carfilzomib

Serious events: 92 serious events

Other events: 141 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Amgen, Inc.

Phone: 866-572-6436

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER