Once-weekly Versus Twice-weekly Carfilzomib in Combination With Dexamethasone in Adults With Relapsed and Refractory Multiple Myeloma (ARROW)

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ClinicalTrials.gov Identifier: NCT02412878

Recruitment Status : Completed

First Posted : April 9, 2015

Results First Posted : December 13, 2018

Last Update Posted : September 23, 2022

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Sponsor:

Information provided by (Responsible Party):

Amgen

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Multiple Myeloma
Interventions	Drug: Carfilzomib Drug: Dexamethasone
Enrollment	478

Participant Flow

Recruitment Details

Participants were enrolled from September 2015 to August 2016 at 118 sites in Australia, New Zealand, Japan, North America, and Europe.

Pre-assignment Details

Participants were randomized in a 1:1 ratio to receive a regimen consisting of either once-weekly or twice weekly carfilzomib in combination with dexamethasone.

Randomization was stratified by International Staging System (ISS) stage (stage 1 vs stages 2 or 3), refractory to bortezomib treatment (yes vs no), and age (< 65 vs ≥ 65 years).


Arm/Group Title	Twice-weekly Carfilzomib 20/27 mg/m² + Dexamethasone	Once-weekly Carfilzomib 20/70 mg/m² + Dexamethasone
Arm/Group Description	Participants received carfilzomib a...	Participants received carfilzomib a...
Arm/Group Description	Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.	Participants received carfilzomib administered by IV infusion on days 1, 8, and 15 of each 28-day cycle (20 mg/m² on day 1 of cycle 1 and 70 mg/m² thereafter). Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Period Title: Overall Study
Started	238	240
Received Carfilzomib	235	238
Completed ^[1]	217	227
Not Completed	21	13
Reason Not Completed
Withdrawal by Subject	19	10
Lost to Follow-up	2	3
[1] Defined as participants who discontinued due to death or study closure

Baseline Characteristics

Arm/Group Title		Twice-weekly Carfilzomib 20/27 mg/m² + Dexamethasone	Once-weekly Carfilzomib 20/70 mg/m² + Dexamethasone	Total
Arm/Group Description		Participants received carfilzomib a...	Participants received carfilzomib a...	Total of all reporting groups
Arm/Group Description		Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.	Participants received carfilzomib administered by IV infusion on days 1, 8, and 15 of each 28-day cycle (20 mg/m² on day 1 of cycle 1 and 70 mg/m² thereafter). Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.	Total of all reporting groups
Overall Number of Baseline Participants		238	240	478
Baseline Analysis Population Description		...
Baseline Analysis Population Description		The intention-to-treat population consisted of all randomly assigned participants.
Age, Continuous Median (Full Range) Unit of measure: Years
	Number Analyzed	238 participants	240 participants	478 participants
		66.0 (35 to 83)	66.0 (39 to 85)	66.0 (35 to 85)
Age, Customized Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	238 participants	240 participants	478 participants
	18 - 64 years	104 43.7%	104 43.3%	208 43.5%
	65 - 74 years	102 42.9%	90 37.5%	192 40.2%
	75 - 84 years	32 13.4%	45 18.8%	77 16.1%
	≥ 85 years	0 0.0%	1 0.4%	1 0.2%
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	238 participants	240 participants	478 participants
	Female	110 46.2%	108 45.0%	218 45.6%
	Male	128 53.8%	132 55.0%	260 54.4%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	238 participants	240 participants	478 participants
	Hispanic or Latino	5 2.1%	2 0.8%	7 1.5%
	Not Hispanic or Latino	226 95.0%	235 97.9%	461 96.4%
	Unknown or Not Reported	7 2.9%	3 1.3%	10 2.1%
Race/Ethnicity, Customized Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	238 participants	240 participants	478 participants
	Asian	15 6.3%	30 12.5%	45 9.4%
	Black or African American	2 0.8%	3 1.3%	5 1.0%
	White	202 84.9%	200 83.3%	402 84.1%
	Other	9 3.8%	4 1.7%	13 2.7%
	Missing	10 4.2%	3 1.3%	13 2.7%
Eastern Cooperative Oncology Group (ECOG) Performance Status ^[1] Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	238 participants	240 participants	478 participants
	0 (Fully active)	118 49.6%	118 49.2%	236 49.4%
	1 (Restrictive but ambulatory)	120 50.4%	121 50.4%	241 50.4%
	2 (Ambulatory but unable to work)	0 0.0%	1 0.4%	1 0.2%
		[1] Measure Description: A scale to assess a patient's disease status. 0 = Fully active, able to carry out all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity, ambulatory and able to carry out work of a light nature; 2 = Ambulatory and capable of all self-care, unable to carry out any work activities. Up and about > 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair > 50% of waking hours; 4 = Completely disabled, confined to bed or chair; 5 = Dead.
Stratification Factor: International Staging System (ISS) stage ^[1] Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	238 participants	240 participants	478 participants
	Stage 1	100 42.0%	100 41.7%	200 41.8%
	Stage 2 or 3	138 58.0%	140 58.3%	278 58.2%
		[1] Measure Description: The International Staging System (ISS) for myeloma was published by the International Myeloma Working Group: Stage I: β2-microglobulin (β2M) < 3.5 mg/L, albumin >= 3.5 g/dL Stage II: β2M < 3.5 mg/L and albumin < 3.5 g/dL; or β2M 3.5 mg/L - 5.5 mg/L irrespective of the serum albumin Stage III: β2M ≥ 5.5 mg/L
Stratification Factor: Refractory to Bortezomib Treatment ^[1] Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	238 participants	240 participants	478 participants
	Yes	88 37.0%	88 36.7%	176 36.8%
	No	150 63.0%	152 63.3%	302 63.2%
		[1] Measure Description: Participants were classified as refractory to bortezomib in prior regimens if the data collected on prior multiple myeloma therapy indicated that any of the following criteria were met: Best Response to any regimen containing bortezomib was stable disease or progressive disease. Reason bortezomib was stopped was progression in any regimen. Date of relapse/progression was after start date and within 60 days after stop date of bortezomib in any regimen.

Outcome Measures

1.Primary Outcome


Title	Progression Free Survival
Description	Progression-free survival (PFS) was defined as the time from randomiza...
Description	Progression-free survival (PFS) was defined as the time from randomization to the earlier of disease progression or death due to any cause. Disease status was assessed at a central laboratory with serum and urine protein electrophoresis, immunofixation, serum-free light chain (SFLC) assay, bone marrow sample evaluation, serum calcium, plasmacytoma evaluation, and skeletal survey. Response and disease progression were determined using a validated computer algorithm based on the International Myeloma Working Group-Uniform Response Criteria (IMWG-URC). Median PFS was derived using the Kaplan-Meier method; participants still alive with no disease progression were censored at the time of their last disease assessment.
Time Frame	From randomization until the data cut-off date of 15 June 2017; median (minimum, maximum) follow-up time for PFS was 12.0 (0, 20) and 12.6 (0, 19) months in each treatment group respectively.

Outcome Measure Data

Analysis Population Description

Intent-to-treat population


Arm/Group Title	Twice-weekly Carfilzomib 20/27 mg/m² + Dexamethasone	Once-weekly Carfilzomib 20/70 mg/m² + Dexamethasone
Arm/Group Description:	Participants received carfilzomib a...	Participants received carfilzomib a...
Arm/Group Description:	Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.	Participants received carfilzomib administered by IV infusion on days 1, 8, and 15 of each 28-day cycle (20 mg/m² on day 1 of cycle 1 and 70 mg/m² thereafter). Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Overall Number of Participants Analyzed	238	240
Median (95% Confidence Interval) Unit of Measure: months
	7.6 (5.8 to 9.2)	11.2 (8.6 to 13.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Twice-weekly Carfilzomib 20/27 mg/m² + Dexamethasone, Once-weekly Carfilzomib 20/70 mg/m² + Dexamethasone
	Comments	To ensure proper control of type I error, analysis of PFS was performed under a group sequential design framework with the stopping boundaries constructed using the Lan-DeMets spending function with an O'Brien-Fleming approach. The inferential comparison between the 2 treatment groups for PFS used the 1-sided log-rank test stratified by the randomization stratification factors. A 1-sided p-value was compared against the prespecified adjusted alpha value of 0.011 to determine significance.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0014
	Comments	Progression-free survival, overall response rate, and overall survival were tested using a fixed sequence hierarchical testing procedure to control the family-wise type I error rate below one-sided 0.025 level.
	Method	Log Rank
	Comments	One-sided stratified log-rank test, stratified by the randomization factors (ISS stage at study entry, refractory to bortezomib treatment, and age).

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.693
	Confidence Interval	(2-Sided) 95% 0.544 to 0.883
	Estimation Comments	Hazard ratio (once weekly carfilzomib 20/70 mg/m²/ twice weekly carfilzomib 20/27 mg/m²) was estimated using a Cox proportional hazards model stratified by the randomization stratification factors.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Twice-weekly Carfilzomib 20/27 mg/m² + Dexamethasone, Once-weekly Carfilzomib 20/70 mg/m² + Dexamethasone
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0033
	Comments	[Not Specified]
	Method	Log Rank
	Comments	One-sided unstratified log-rank test

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.720
	Confidence Interval	(2-Sided) 95% 0.567 to 0.913
	Estimation Comments	Hazard ratio (once weekly carfilzomib 20/70 mg/m²/ twice weekly carfilzomib 20/27 mg/m²) was estimated using an unstratified Cox proportional hazards model.

2.Secondary Outcome


Title	Overall Response Rate
Description	Disease response was evaluated according to the IMWG-URC using a valid...
Description	Disease response was evaluated according to the IMWG-URC using a validated computer algorithm. Overall response rate was defined as the percentage of participants with a best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR). sCR: As for CR, normal serum free light chain (SFLC) ratio and no clonal cells in bone marrow (BM). CR: No immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and < 5% plasma cells in BM biopsy; VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% reduction in serum M-protein with urine M-protein <100 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline. PR: ≥ 50% reduction of serum M-protein and reduction in urine M-protein by ≥ 90% or to < 200 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline.
Time Frame	Disease response was assessed every 28 days until progressive disease, up to the data cut-off date of 15 June 2017; median time on follow-up was 12.0 and 12.6 months in each treatment group respectively.

Outcome Measure Data

Analysis Population Description

Intent-to-treat population


Arm/Group Title	Twice-weekly Carfilzomib 20/27 mg/m² + Dexamethasone	Once-weekly Carfilzomib 20/70 mg/m² + Dexamethasone
Arm/Group Description:	Participants received carfilzomib a...	Participants received carfilzomib a...
Arm/Group Description:	Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.	Participants received carfilzomib administered by IV infusion on days 1, 8, and 15 of each 28-day cycle (20 mg/m² on day 1 of cycle 1 and 70 mg/m² thereafter). Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Overall Number of Participants Analyzed	238	240
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	40.8 (34.5 to 47.3)	62.9 (56.5 to 69.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Twice-weekly Carfilzomib 20/27 mg/m² + Dexamethasone, Once-weekly Carfilzomib 20/70 mg/m² + Dexamethasone
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	< 0.0001
	Comments	Progression-free survival, overall response, and overall survival were tested using a fixed sequence hierarchical testing procedure to control the family-wise type I error rate below one-sided 0.025 level.
	Method	Cochran-Mantel-Haenszel
	Comments	One-sided p-value from CMH test stratified by the randomization factors (ISS stage at study entry, refractory to bortezomib treatment, and age).

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.485
	Confidence Interval	(2-Sided) 95% 1.716 to 3.598
	Estimation Comments	Odds ratio (once weekly carfilzomib 20/70 mg/m²/ twice weekly carfilzomib 20/27 mg/m²) was calculated using the Mantel-Haenszel method stratified by the randomization stratification factors.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Twice-weekly Carfilzomib 20/27 mg/m² + Dexamethasone, Once-weekly Carfilzomib 20/70 mg/m² + Dexamethasone
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.466
	Confidence Interval	(2-Sided) 95% 1.707 to 3.563
	Estimation Comments	Odds ratio (once weekly carfilzomib 20/70 mg/m²/ twice weekly carfilzomib 20/27 mg/m²) was calculated using the Mantel-Haenszel method.

3.Secondary Outcome


Title	Overall Survival
Description	Overall Survival (OS) was defined as the time from randomization to de...
Description	Overall Survival (OS) was defined as the time from randomization to death due to any cause. Median overall survival was derived using the Kaplan-Meier method; participants still alive were censored at the date last known to be alive.
Time Frame	From randomization until the data cut-off date of 15 June 2017; median (minimum, maximum) follow-up time for OS was 12.6 (0, 20) and 13.2 (0, 19) months in each treatment group respectively.

Outcome Measure Data

Analysis Population Description

Intent-to-treat population


Arm/Group Title	Twice-weekly Carfilzomib 20/27 mg/m² + Dexamethasone	Once-weekly Carfilzomib 20/70 mg/m² + Dexamethasone
Arm/Group Description:	Participants received carfilzomib a...	Participants received carfilzomib a...
Arm/Group Description:	Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.	Participants received carfilzomib administered by IV infusion on days 1, 8, and 15 of each 28-day cycle (20 mg/m² on day 1 of cycle 1 and 70 mg/m² thereafter). Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Overall Number of Participants Analyzed	238	240
Median (95% Confidence Interval) Unit of Measure: months
	NA ^[1] (18.1 to NA)	NA ^[1] (NA to NA)

[1]

Could not be estimated due to the low number of events

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Twice-weekly Carfilzomib 20/27 mg/m² + Dexamethasone, Once-weekly Carfilzomib 20/70 mg/m² + Dexamethasone
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.1070
	Comments	Progression-free survival, overall response, and overall survival were tested using a fixed sequence hierarchical testing procedure to control the family-wise type I error rate below one-sided 0.025 level.
	Method	Log Rank
	Comments	One-sided stratified log-rank test, stratified by the randomization factors (ISS stage at study entry, refractory to bortezomib treatment, and age).

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.800
	Confidence Interval	(2-Sided) 95% 0.563 to 1.138
	Estimation Comments	Hazard ratio (once weekly carfilzomib 20/70 mg/m²/ twice weekly carfilzomib 20/27 mg/m²) was estimated using a Cox proportional hazards model stratified by the randomization stratification factors.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Twice-weekly Carfilzomib 20/27 mg/m² + Dexamethasone, Once-weekly Carfilzomib 20/70 mg/m² + Dexamethasone
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.1326
	Comments	[Not Specified]
	Method	Log Rank
	Comments	One-sided unstratified log-rank test

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.820
	Confidence Interval	(2-Sided) 95% 0.578 to 1.164
	Estimation Comments	Hazard ratio (once weekly carfilzomib 20/70 mg/m²/ twice weekly carfilzomib 20/27 mg/m²) was estimated using an unstratified Cox proportional hazards model.

4.Secondary Outcome


Title	Number of Participants With Adverse Events (AEs)
Description	The severity of adverse events was graded according to the National Ca...
Description	The severity of adverse events was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03, where where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening; Grade 5 = Fatal. Treatment-related adverse events are adverse events considered related to at least 1 investigational product by the investigator, including those with unknown relationship.
Time Frame	From first dose of study drug up to 30 days after last dose, up to the end of study; median (minimum, maximum) duration of treatment was 29.1 (0.1, 156.3) weeks and 38.0 (0.1, 158.3) weeks in each treatment group respectively.

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug


Arm/Group Title	Twice-weekly Carfilzomib 20/27 mg/m² + Dexamethasone	Once-weekly Carfilzomib 20/70 mg/m² + Dexamethasone
Arm/Group Description:	Participants received carfilzomib a...	Participants received carfilzomib a...
Arm/Group Description:	Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.	Participants received carfilzomib administered by IV infusion on days 1, 8, and 15 of each 28-day cycle (20 mg/m² on day 1 of cycle 1 and 70 mg/m² thereafter). Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Overall Number of Participants Analyzed	235	238
Measure Type: Count of Participants Unit of Measure: Participants
Adverse events (AEs)	230 97.9%	233 97.9%
Adverse events Grade ≥ 3	152 64.7%	181 76.1%
Serious adverse events	102 43.4%	118 49.6%
AEs leading to discontinuation of carfilzomib	29 12.3%	35 14.7%
AEs leading to discontinuation of dexamethasone	31 13.2%	40 16.8%
Fatal adverse events	20 8.5%	21 8.8%
Treatment-related adverse events (TRAEs)	176 74.9%	180 75.6%
Treatment-related adverse events Grade ≥ 3	82 34.9%	108 45.4%
Serious treatment-related adverse events	31 13.2%	57 23.9%
TRAE leading to discontinuation of carfilzomib	11 4.7%	23 9.7%
TRAEs leading to discontinuation of dexamethasone	13 5.5%	29 12.2%
Fatal treatment-related adverse events	3 1.3%	5 2.1%

5.Secondary Outcome


Title	Plasma Carfilzomib Concentration During Cycle 2
Description	Concentrations of carfilzomib in plasma were measured using a validate...
Description	Concentrations of carfilzomib in plasma were measured using a validated assay method. The lower limit of quantification was 0.100 ng/mL.
Time Frame	Cycle 2 day 1 predose, 15 minutes after the start of infusion (once-weekly carfilzomib only), end of infusion, and 30 minutes after the end of infusion

Outcome Measure Data

Analysis Population Description

Participants at a subset of sites who participated in the sparse pharmacokinetic sampling, with available data at each time point.


Arm/Group Title		Twice-weekly Carfilzomib 20/27 mg/m² + Dexamethasone	Once-weekly Carfilzomib 20/70 mg/m² + Dexamethasone
Arm/Group Description:		Participants received carfilzomib a...	Participants received carfilzomib a...
Arm/Group Description:		Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.	Participants received carfilzomib administered by IV infusion on days 1, 8, and 15 of each 28-day cycle (20 mg/m² on day 1 of cycle 1 and 70 mg/m² thereafter). Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Overall Number of Participants Analyzed		36	55
Mean (Standard Deviation) Unit of Measure: ng/mL
Predose	Number Analyzed	36 participants	55 participants
Predose		36.2 (162)	203 (1380)
15 minutes after start of infusion	Number Analyzed	0 participants	46 participants
15 minutes after start of infusion			1370 (1410)
End of infusion	Number Analyzed	10 participants	51 participants
End of infusion		1640 (1900)	1130 (928)
30 minutes after end of infusion	Number Analyzed	27 participants	46 participants
30 minutes after end of infusion		104 (293)	480 (2300)

Adverse Events

Time Frame	All-cause mortality includes deaths that occurred from randomization until the end of study; median (minimum, maximum) follow-up time was 30.7 (0, 39) and 31.2 (0, 38) months in each treatment group respectively. Adverse events are reported from the first dose of study drug up to 30 days after last dose, as of the end of study; median (minimum, maximum) duration of treatment was 29.1 (0.1, 156.3) weeks and 38.0 (0.1, 158.3) weeks in each treatment group respectively.
Adverse Event Reporting Description	All-cause mortality is reported for all participants randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.

Arm/Group Title	Twice-weekly Carfilzomib 20/27 mg/m² + Dexamethasone	Once-weekly Carfilzomib 20/70 mg/m² + Dexamethasone
Arm/Group Description	Participants received carfilzomib a...	Participants received carfilzomib a...
Arm/Group Description	Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.	Participants received carfilzomib administered by IV infusion on days 1, 8, and 15 of each 28-day cycle (20 mg/m² on day 1 of cycle 1 and 70 mg/m² thereafter). Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
All-Cause Mortality
	Twice-weekly Carfilzomib 20/27 mg/m² + Dexamethasone	Once-weekly Carfilzomib 20/70 mg/m² + Dexamethasone
	Affected / at Risk (%)	Affected / at Risk (%)
Total	127/238 (53.36%)	119/240 (49.58%)
Serious Adverse Events Serious Adverse Events
	Twice-weekly Carfilzomib 20/27 mg/m² + Dexamethasone	Once-weekly Carfilzomib 20/70 mg/m² + Dexamethasone
	Affected / at Risk (%)	Affected / at Risk (%)
Total	102/235 (43.40%)	118/238 (49.58%)
Blood and lymphatic system disorders
Anaemia ^† 1	8/235 (3.40%)	4/238 (1.68%)
Anaemia folate deficiency ^† 1	1/235 (0.43%)	0/238 (0.00%)
Anaemia vitamin B12 deficiency ^† 1	1/235 (0.43%)	0/238 (0.00%)
Febrile neutropenia ^† 1	0/235 (0.00%)	1/238 (0.42%)
Haemolytic uraemic syndrome ^† 1	0/235 (0.00%)	1/238 (0.42%)
Hyperviscosity syndrome ^† 1	0/235 (0.00%)	1/238 (0.42%)
Thrombocytopenia ^† 1	3/235 (1.28%)	3/238 (1.26%)
Thrombotic microangiopathy ^† 1	0/235 (0.00%)	2/238 (0.84%)
Cardiac disorders
Acute myocardial infarction ^† 1	1/235 (0.43%)	2/238 (0.84%)
Atrial fibrillation ^† 1	3/235 (1.28%)	2/238 (0.84%)
Atrial flutter ^† 1	0/235 (0.00%)	1/238 (0.42%)
Cardiac arrest ^† 1	1/235 (0.43%)	1/238 (0.42%)
Cardiac failure ^† 1	3/235 (1.28%)	3/238 (1.26%)
Cardiac failure acute ^† 1	2/235 (0.85%)	3/238 (1.26%)
Cardiac failure congestive ^† 1	3/235 (1.28%)	1/238 (0.42%)
Cardiopulmonary failure ^† 1	0/235 (0.00%)	1/238 (0.42%)
Left ventricular dysfunction ^† 1	1/235 (0.43%)	0/238 (0.00%)
Myocardial ischaemia ^† 1	0/235 (0.00%)	1/238 (0.42%)
Stress cardiomyopathy ^† 1	1/235 (0.43%)	0/238 (0.00%)
Supraventricular tachycardia ^† 1	1/235 (0.43%)	0/238 (0.00%)
Endocrine disorders
Adrenal insufficiency ^† 1	1/235 (0.43%)	0/238 (0.00%)
Eye disorders
Cataract ^† 1	2/235 (0.85%)	1/238 (0.42%)
Retinal detachment ^† 1	1/235 (0.43%)	1/238 (0.42%)
Retinal vein occlusion ^† 1	1/235 (0.43%)	0/238 (0.00%)
Gastrointestinal disorders
Diarrhoea ^† 1	1/235 (0.43%)	1/238 (0.42%)
Gastric haemorrhage ^† 1	0/235 (0.00%)	1/238 (0.42%)
Gastritis ^† 1	0/235 (0.00%)	1/238 (0.42%)
Nausea ^† 1	0/235 (0.00%)	1/238 (0.42%)
Pancreatitis ^† 1	1/235 (0.43%)	0/238 (0.00%)
Peritoneal haematoma ^† 1	0/235 (0.00%)	1/238 (0.42%)
Rectal haemorrhage ^† 1	1/235 (0.43%)	0/238 (0.00%)
Retroperitoneal haematoma ^† 1	0/235 (0.00%)	1/238 (0.42%)
Mallory-Weiss syndrome ^† 1	0/235 (0.00%)	1/238 (0.42%)
General disorders
Asthenia ^† 1	0/235 (0.00%)	2/238 (0.84%)
Catheter site vesicles ^† 1	1/235 (0.43%)	0/238 (0.00%)
Chest pain ^† 1	0/235 (0.00%)	1/238 (0.42%)
Critical illness ^† 1	1/235 (0.43%)	0/238 (0.00%)
Death ^† 1	1/235 (0.43%)	1/238 (0.42%)
Disease progression ^† 1	3/235 (1.28%)	2/238 (0.84%)
Fatigue ^† 1	0/235 (0.00%)	3/238 (1.26%)
Papillitis ^† 1	1/235 (0.43%)	0/238 (0.00%)
Pyrexia ^† 1	5/235 (2.13%)	4/238 (1.68%)
Drug intolerance ^† 1	0/235 (0.00%)	1/238 (0.42%)
Non-cardiac chest pain ^† 1	0/235 (0.00%)	2/238 (0.84%)
Hepatobiliary disorders
Cholecystitis acute ^† 1	1/235 (0.43%)	0/238 (0.00%)
Hepatic failure ^† 1	1/235 (0.43%)	0/238 (0.00%)
Cholecystitis ^† 1	1/235 (0.43%)	0/238 (0.00%)
Infections and infestations
Bronchitis ^† 1	4/235 (1.70%)	1/238 (0.42%)
Bronchitis bacterial ^† 1	0/235 (0.00%)	1/238 (0.42%)
Bronchopulmonary aspergillosis ^† 1	1/235 (0.43%)	0/238 (0.00%)
Diverticulitis ^† 1	1/235 (0.43%)	0/238 (0.00%)
Erysipelas ^† 1	1/235 (0.43%)	0/238 (0.00%)
Gastroenteritis ^† 1	1/235 (0.43%)	1/238 (0.42%)
Infected skin ulcer ^† 1	1/235 (0.43%)	0/238 (0.00%)
Infection ^† 1	2/235 (0.85%)	4/238 (1.68%)
Influenza ^† 1	2/235 (0.85%)	4/238 (1.68%)
Lower respiratory tract infection ^† 1	1/235 (0.43%)	2/238 (0.84%)
Lower respiratory tract infection viral ^† 1	1/235 (0.43%)	0/238 (0.00%)
Lung infection ^† 1	0/235 (0.00%)	3/238 (1.26%)
Lung infection pseudomonal ^† 1	0/235 (0.00%)	1/238 (0.42%)
Neutropenic infection ^† 1	1/235 (0.43%)	0/238 (0.00%)
Osteomyelitis ^† 1	1/235 (0.43%)	0/238 (0.00%)
Otitis media acute ^† 1	0/235 (0.00%)	1/238 (0.42%)
Periodontitis ^† 1	1/235 (0.43%)	0/238 (0.00%)
Pneumonia ^† 1	22/235 (9.36%)	23/238 (9.66%)
Pneumonia bacterial ^† 1	3/235 (1.28%)	3/238 (1.26%)
Pneumonia haemophilus ^† 1	0/235 (0.00%)	1/238 (0.42%)
Pneumonia streptococcal ^† 1	1/235 (0.43%)	0/238 (0.00%)
Pyelonephritis acute ^† 1	1/235 (0.43%)	0/238 (0.00%)
Respiratory syncytial virus infection ^† 1	2/235 (0.85%)	0/238 (0.00%)
Respiratory tract infection ^† 1	1/235 (0.43%)	3/238 (1.26%)
Sepsis ^† 1	3/235 (1.28%)	6/238 (2.52%)
Septic shock ^† 1	2/235 (0.85%)	5/238 (2.10%)
Spinal cord infection ^† 1	1/235 (0.43%)	0/238 (0.00%)
Upper respiratory tract infection ^† 1	4/235 (1.70%)	1/238 (0.42%)
Urinary tract infection ^† 1	1/235 (0.43%)	2/238 (0.84%)
Wound infection bacterial ^† 1	1/235 (0.43%)	0/238 (0.00%)
Gastroenteritis viral ^† 1	0/235 (0.00%)	1/238 (0.42%)
Perineal abscess ^† 1	1/235 (0.43%)	0/238 (0.00%)
Post procedural sepsis ^† 1	0/235 (0.00%)	1/238 (0.42%)
Respiratory tract infection viral ^† 1	0/235 (0.00%)	1/238 (0.42%)
Staphylococcal sepsis ^† 1	0/235 (0.00%)	1/238 (0.42%)
Injury, poisoning and procedural complications
Contusion ^† 1	1/235 (0.43%)	0/238 (0.00%)
Fall ^† 1	1/235 (0.43%)	0/238 (0.00%)
Femoral neck fracture ^† 1	1/235 (0.43%)	1/238 (0.42%)
Femur fracture ^† 1	1/235 (0.43%)	1/238 (0.42%)
Infusion related reaction ^† 1	1/235 (0.43%)	1/238 (0.42%)
Limb traumatic amputation ^† 1	1/235 (0.43%)	0/238 (0.00%)
Rib fracture ^† 1	2/235 (0.85%)	0/238 (0.00%)
Upper limb fracture ^† 1	0/235 (0.00%)	1/238 (0.42%)
Humerus fracture ^† 1	1/235 (0.43%)	0/238 (0.00%)
Tibia fracture ^† 1	0/235 (0.00%)	1/238 (0.42%)
Traumatic fracture ^† 1	0/235 (0.00%)	1/238 (0.42%)
Investigations
Alanine aminotransferase increased ^† 1	0/235 (0.00%)	1/238 (0.42%)
Aspartate aminotransferase increased ^† 1	0/235 (0.00%)	1/238 (0.42%)
Blood creatinine increased ^† 1	2/235 (0.85%)	1/238 (0.42%)
Blood lactate dehydrogenase increased ^† 1	0/235 (0.00%)	1/238 (0.42%)
C-reactive protein increased ^† 1	0/235 (0.00%)	1/238 (0.42%)
Ejection fraction decreased ^† 1	1/235 (0.43%)	1/238 (0.42%)
Liver function test abnormal ^† 1	1/235 (0.43%)	0/238 (0.00%)
Platelet count decreased ^† 1	2/235 (0.85%)	2/238 (0.84%)
General physical condition abnormal ^† 1	1/235 (0.43%)	0/238 (0.00%)
Monoclonal immunoglobulin present ^† 1	0/235 (0.00%)	1/238 (0.42%)
Metabolism and nutrition disorders
Dehydration ^† 1	0/235 (0.00%)	1/238 (0.42%)
Diabetes mellitus ^† 1	1/235 (0.43%)	0/238 (0.00%)
Hypercalcaemia ^† 1	4/235 (1.70%)	2/238 (0.84%)
Hyperglycaemia ^† 1	1/235 (0.43%)	0/238 (0.00%)
Hyperuricaemia ^† 1	0/235 (0.00%)	1/238 (0.42%)
Tumour lysis syndrome ^† 1	1/235 (0.43%)	4/238 (1.68%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	1/235 (0.43%)	0/238 (0.00%)
Back pain ^† 1	2/235 (0.85%)	0/238 (0.00%)
Bone pain ^† 1	1/235 (0.43%)	2/238 (0.84%)
Osteolysis ^† 1	1/235 (0.43%)	1/238 (0.42%)
Pain in extremity ^† 1	1/235 (0.43%)	0/238 (0.00%)
Pathological fracture ^† 1	1/235 (0.43%)	3/238 (1.26%)
Bone lesion ^† 1	0/235 (0.00%)	1/238 (0.42%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma ^† 1	0/235 (0.00%)	1/238 (0.42%)
Myelodysplastic syndrome ^† 1	0/235 (0.00%)	1/238 (0.42%)
Plasma cell leukaemia ^† 1	1/235 (0.43%)	0/238 (0.00%)
Plasma cell myeloma ^† 1	7/235 (2.98%)	4/238 (1.68%)
Plasmacytoma ^† 1	1/235 (0.43%)	1/238 (0.42%)
Urethral neoplasm ^† 1	1/235 (0.43%)	0/238 (0.00%)
Bladder transitional cell carcinoma ^† 1	0/235 (0.00%)	1/238 (0.42%)
Nervous system disorders
Altered state of consciousness ^† 1	0/235 (0.00%)	1/238 (0.42%)
Cerebral haemorrhage ^† 1	0/235 (0.00%)	1/238 (0.42%)
Cerebrovascular accident ^† 1	0/235 (0.00%)	1/238 (0.42%)
Intracranial mass ^† 1	0/235 (0.00%)	1/238 (0.42%)
Spinal cord compression ^† 1	0/235 (0.00%)	1/238 (0.42%)
Syncope ^† 1	0/235 (0.00%)	1/238 (0.42%)
Haemorrhage intracranial ^† 1	0/235 (0.00%)	1/238 (0.42%)
Psychiatric disorders
Bradyphrenia ^† 1	0/235 (0.00%)	1/238 (0.42%)
Delirium ^† 1	1/235 (0.43%)	0/238 (0.00%)
Renal and urinary disorders
Acute kidney injury ^† 1	8/235 (3.40%)	12/238 (5.04%)
Renal failure ^† 1	3/235 (1.28%)	1/238 (0.42%)
Renal impairment ^† 1	1/235 (0.43%)	0/238 (0.00%)
Chronic kidney disease ^† 1	0/235 (0.00%)	1/238 (0.42%)
Urinary bladder polyp ^† 1	0/235 (0.00%)	1/238 (0.42%)
Reproductive system and breast disorders
Pelvic pain ^† 1	1/235 (0.43%)	0/238 (0.00%)
Respiratory, thoracic and mediastinal disorders
Acute lung injury ^† 1	0/235 (0.00%)	2/238 (0.84%)
Acute respiratory distress syndrome ^† 1	0/235 (0.00%)	1/238 (0.42%)
Aspiration ^† 1	1/235 (0.43%)	0/238 (0.00%)
Dyspnoea ^† 1	1/235 (0.43%)	0/238 (0.00%)
Epistaxis ^† 1	1/235 (0.43%)	1/238 (0.42%)
Hypoxia ^† 1	1/235 (0.43%)	0/238 (0.00%)
Interstitial lung disease ^† 1	0/235 (0.00%)	1/238 (0.42%)
Lung consolidation ^† 1	1/235 (0.43%)	0/238 (0.00%)
Pleural effusion ^† 1	2/235 (0.85%)	1/238 (0.42%)
Pulmonary alveolar haemorrhage ^† 1	0/235 (0.00%)	1/238 (0.42%)
Pulmonary arterial hypertension ^† 1	0/235 (0.00%)	1/238 (0.42%)
Pulmonary congestion ^† 1	0/235 (0.00%)	1/238 (0.42%)
Pulmonary embolism ^† 1	0/235 (0.00%)	6/238 (2.52%)
Pulmonary hypertension ^† 1	0/235 (0.00%)	1/238 (0.42%)
Pulmonary oedema ^† 1	1/235 (0.43%)	0/238 (0.00%)
Respiratory failure ^† 1	2/235 (0.85%)	0/238 (0.00%)
Social circumstances
Homicide ^† 1	0/235 (0.00%)	1/238 (0.42%)
Vascular disorders
Deep vein thrombosis ^† 1	4/235 (1.70%)	0/238 (0.00%)
Hypertension ^† 1	1/235 (0.43%)	0/238 (0.00%)
Hypotension ^† 1	1/235 (0.43%)	0/238 (0.00%)
Pelvic venous thrombosis ^† 1	0/235 (0.00%)	1/238 (0.42%)
1 Term from vocabulary, MedDRA 21.1 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Twice-weekly Carfilzomib 20/27 mg/m² + Dexamethasone	Once-weekly Carfilzomib 20/70 mg/m² + Dexamethasone
	Affected / at Risk (%)	Affected / at Risk (%)
Total	204/235 (86.81%)	217/238 (91.18%)
Blood and lymphatic system disorders
Anaemia ^† 1	73/235 (31.06%)	69/238 (28.99%)
Neutropenia ^† 1	23/235 (9.79%)	20/238 (8.40%)
Thrombocytopenia ^† 1	19/235 (8.09%)	30/238 (12.61%)
Eye disorders
Cataract ^† 1	13/235 (5.53%)	14/238 (5.88%)
Gastrointestinal disorders
Constipation ^† 1	22/235 (9.36%)	21/238 (8.82%)
Diarrhoea ^† 1	51/235 (21.70%)	53/238 (22.27%)
Nausea ^† 1	30/235 (12.77%)	38/238 (15.97%)
Vomiting ^† 1	17/235 (7.23%)	25/238 (10.50%)
General disorders
Asthenia ^† 1	29/235 (12.34%)	29/238 (12.18%)
Fatigue ^† 1	47/235 (20.00%)	50/238 (21.01%)
Oedema peripheral ^† 1	26/235 (11.06%)	23/238 (9.66%)
Pyrexia ^† 1	38/235 (16.17%)	55/238 (23.11%)
Chest pain ^† 1	4/235 (1.70%)	12/238 (5.04%)
Infections and infestations
Bronchitis ^† 1	25/235 (10.64%)	31/238 (13.03%)
Respiratory tract infection ^† 1	23/235 (9.79%)	18/238 (7.56%)
Upper respiratory tract infection ^† 1	28/235 (11.91%)	39/238 (16.39%)
Influenza ^† 1	9/235 (3.83%)	13/238 (5.46%)
Nasopharyngitis ^† 1	30/235 (12.77%)	35/238 (14.71%)
Pneumonia ^† 1	5/235 (2.13%)	15/238 (6.30%)
Investigations
Blood creatinine increased ^† 1	8/235 (3.40%)	14/238 (5.88%)
Neutrophil count decreased ^† 1	5/235 (2.13%)	12/238 (5.04%)
Platelet count decreased ^† 1	21/235 (8.94%)	27/238 (11.34%)
Metabolism and nutrition disorders
Decreased appetite ^† 1	14/235 (5.96%)	14/238 (5.88%)
Hypokalaemia ^† 1	10/235 (4.26%)	20/238 (8.40%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	15/235 (6.38%)	19/238 (7.98%)
Back pain ^† 1	31/235 (13.19%)	35/238 (14.71%)
Bone pain ^† 1	17/235 (7.23%)	20/238 (8.40%)
Muscle spasms ^† 1	20/235 (8.51%)	22/238 (9.24%)
Musculoskeletal pain ^† 1	12/235 (5.11%)	14/238 (5.88%)
Pain in extremity ^† 1	19/235 (8.09%)	17/238 (7.14%)
Nervous system disorders
Headache ^† 1	25/235 (10.64%)	28/238 (11.76%)
Psychiatric disorders
Insomnia ^† 1	49/235 (20.85%)	39/238 (16.39%)
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	33/235 (14.04%)	44/238 (18.49%)
Dyspnoea ^† 1	21/235 (8.94%)	27/238 (11.34%)
Skin and subcutaneous tissue disorders
Rash ^† 1	13/235 (5.53%)	9/238 (3.78%)
Vascular disorders
Hypertension ^† 1	49/235 (20.85%)	58/238 (24.37%)
1 Term from vocabulary, MedDRA 21.1 † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Study Director
Organization:	Amgen Inc.
Phone:	866-572-6436
EMail:	medinfo@amgen.com

Publications:

Moreau P, Mateos MV, Berenson JR, Weisel K, Lazzaro A, Song K, Dimopoulos MA, Huang M, Zahlten-Kumeli A, Stewart AK. Once weekly versus twice weekly carfilzomib dosing in patients with relapsed and refractory multiple myeloma (A.R.R.O.W.): interim analysis results of a randomised, phase 3 study. Lancet Oncol. 2018 Jul;19(7):953-964. doi: 10.1016/S1470-2045(18)30354-1. Epub 2018 Jun 1. Erratum In: Lancet Oncol. 2018 Aug;19(8):e382.

Facon T, Niesvizky R, Mateos MV, Siegel D, Rosenbaum C, Bringhen S, Weisel K, Ho PJ, Ludwig H, Kumar S, Wang K, Obreja M, Yang Z, Klippel Z, Mezzi K, Goldrick A, Tekle C, Dimopoulos MA. Efficacy and safety of carfilzomib-based regimens in frail patients with relapsed and/or refractory multiple myeloma. Blood Adv. 2020 Nov 10;4(21):5449-5459. doi: 10.1182/bloodadvances.2020001965.

Dimopoulos MA, Niesvizky R, Weisel K, Siegel DS, Hajek R, Mateos MV, Cavo M, Huang M, Zahlten-Kumeli A, Moreau P. Once- versus twice-weekly carfilzomib in relapsed and refractory multiple myeloma by select patient characteristics: phase 3 A.R.R.O.W. study subgroup analysis. Blood Cancer J. 2020 Mar 9;10(3):35. doi: 10.1038/s41408-020-0300-y.

Moreau P, Stewart KA, Dimopoulos M, Siegel D, Facon T, Berenson J, Raje N, Berdeja JG, Orlowski RZ, Yang H, Ma H, Klippel Z, Zahlten-Kumeli A, Mezzi K, Iskander K, Mateos MV. Once-weekly (70 mg/m2 ) vs twice-weekly (56 mg/m2 ) dosing of carfilzomib in patients with relapsed or refractory multiple myeloma: A post hoc analysis of the ENDEAVOR, A.R.R.O.W., and CHAMPION-1 trials. Cancer Med. 2020 May;9(9):2989-2996. doi: 10.1002/cam4.2945. Epub 2020 Feb 28.

Moreau P, Kumar S, Boccia R, Iida S, Goldschmidt H, Cocks K, Trigg A, Zahlten-Kumeli A, Yucel E, Panjabi SS, Dimopoulos M. Convenience, satisfaction, health-related quality of life of once-weekly 70 mg/m2 vs. twice-weekly 27 mg/m2 carfilzomib (randomized A.R.R.O.W. study). Leukemia. 2019 Dec;33(12):2934-2946. doi: 10.1038/s41375-019-0480-2. Epub 2019 May 15.

Kumar SK, Majer I, Panjabi S, Medhekar R, Campioni M, Dimopoulos MA. Cost-effectiveness of once weekly carfilzomib 70 mg/m2 plus dexamethasone in patients with relapsed and refractory multiple myeloma in the United States. Expert Rev Hematol. 2020 Jun;13(6):687-696. doi: 10.1080/17474086.2020.1746639. Epub 2020 Apr 6.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Dimopoulos MA, Moreau P, Iida S, Huang SY, Takezako N, Chng WJ, Zahlten-Kumeli A, Sersch MA, Li J, Huang M, Lee JH. Outcomes for Asian patients with multiple myeloma receiving once- or twice-weekly carfilzomib-based therapy: a subgroup analysis of the randomized phase 3 ENDEAVOR and A.R.R.O.W. Trials. Int J Hematol. 2019 Oct;110(4):466-473. doi: 10.1007/s12185-019-02704-z. Epub 2019 Aug 6.

Layout table for additonal information

Responsible Party:	Amgen
ClinicalTrials.gov Identifier:	NCT02412878
Other Study ID Numbers:	CFZ014 2014-005325-12 ( EudraCT Number ) 20140355 ( Other Identifier: Amgen Study ID )
First Submitted:	April 6, 2015
First Posted:	April 9, 2015
Results First Submitted:	October 24, 2018
Results First Posted:	December 13, 2018
Last Update Posted:	September 23, 2022

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