A Study of Extended Carfilzomib Therapy for Patients Previously Enrolled in Carfilzomib Treatment Protocols

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00884312
• Collaborator: (none)
• Enrollment: 101
• Locations: 23
• Arm: 1
• Actual Duration (Months): 97.2
• Patients Per Site: 4.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This is a multi-center, open-label, Phase 2 study of carfilzomib to monitor the safety and efficacy of long-term or continuing carfilzomib therapy for patients who previously completed a primary carfilzomib treatment study.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma; Solid Tumors	Drug: Carfilzomib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 101 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Single-Arm, Phase 2 Study of Extended Carfilzomib Therapy in Subjects Previously Enrolled in Carfilzomib Treatment Protocols
• Actual Study Start Date: Apr 9, 2009
• Actual Primary Completion Date: May 17, 2017
• Actual Study Completion Date: May 17, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Carfilzomib Participants received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.

Drug: Carfilzomib; Carfilzomib dose levels ranged from 11 to 27 mg/m² for 2- to 10-minute infusions and 36 to 56 mg/m² for 30-minute infusions. Carfilzomib doses were administered on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. Dose level reduction to a minimum dose of 11 mg/m² for toxicity was permitted.; Other Names: PR-171 PR171 Kyprolis®

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Peripheral Neuropathy [From first dose of study drug to 30 days after the last dose; median duration of treatment was 14 weeks for participants with solid tumors and 44 weeks for participants with multiple myeloma.]

   Participants with peripheral neuropathy or peripheral neuropathy-related adverse events, including hypoaesthesia, paraesthesia, dysaesthesia, and neuropathic pain.

2. Number of Participants With Adverse Events [From first dose of study drug to 30 days after the last dose; median duration of treatment was 14 weeks for participants with solid tumors and 44 weeks for participants with multiple myeloma.]

   Adverse events (AEs) were assigned a severity grade using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) grading scale version 3.0. Per protocol, adverse events were collected if they led to dose modification or dose discontinuation, were grade ≥ 3 or serious, or were events of peripheral neuropathy (any grade). A serious AE is one that met one or more of the following criteria: Death Life threatening Required inpatient hospitalization or prolongation of an existing hospitalization Resulted in persistent or significant disability/incapacity A congenital anomaly/birth defect in the offspring of an exposed subject Important medical events that, based upon appropriate medical judgment, jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes above.

Secondary Outcome Measures

1. Overall Survival [From first dose of study drug to 30 days after the last dose; median duration of treatment was 14 weeks for participants with solid tumors and 44 weeks for participants with multiple myeloma.]

   Since participants were only followed up to 30 days after administration of last dose of study drug per protocol, Kaplan-Meier estimates of overall survival were not calculated. The number of participants who died within 30 days after administration of last dose of study drug is reported.

2. Progression-free Survival [From first dose of study drug in study PX-171-010 to 30 days after the last dose; median duration of treatment was 14 weeks for participants with solid tumors and 44 weeks for participants with multiple myeloma.]

   Progression-free survival (PFS) was defined as the time between the start of treatment and first evidence of documented disease progression or death (due to any cause), whichever occurred first. Disease progression was determined by the local investigator for regimens with the same baseline using the International Uniform Response Criteria (IMWG-URC) for participants with multiple myeloma and Response Evaluation Criteria in Solid Tumors (RECIST) criteria for solid tumor participants. PFS was re-calculated whenever the baseline was reset due to addition of new anti-cancer therapy or increase of carfilzomib dose/frequency.

3. Time to Progression [From first dose of study drug in study PX-171-010 to 30 days after the last dose; median duration of treatment was 14 weeks for participants with solid tumors and 44 weeks for participants with multiple myeloma.]

   Time to progression (TTP) was defined as the time between start of treatment to the first documentation of disease progression. TTP was re-calculated whenever the baseline was reset due to addition of new anti-cancer therapy or increase of carfilzomib dose/frequency.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Previous completion of a carfilzomib study within 90 days prior to first dose of maintenance study drug.

2. Disease Assessments performed within 30 days prior to first dose of maintenance study drug.

3. Written informed consent in accordance with federal, local, and institutional guidelines

4. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test, with a sensitivity of at least 50 mIU/mL, within 3 days prior to first dose of maintenance study drug.

5. Subjects must agree to adhere to the study visit schedule and other study requirements and receive outpatient treatment and laboratory monitoring at the institution that administers the drug.

Exclusion Criteria:

1. Administration of an intervening chemotherapy between the time of previous carfilzomib study termination and first dose of maintenance study drug.

2. Pregnant or lactating females

3. Diagnosis of a new malignancy of a different tumor type.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pinnacle Oncology Hematology	Scottsdale	Arizona	United States	85258
2	Tower Cancer Research Foundation	Beverly Hills	California	United States	90211
3	City of Hope National Medial Center	Duarte	California	United States	91010
4	University of California Medical Center	San Francisco	California	United States	94143
5	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
6	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida	United States	33612
7	Winship Cancer Institute - Emory University	Atlanta	Georgia	United States	30322
8	Northwestern University	Chicago	Illinois	United States	60611
9	University of Maryland, Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
10	Washington University School of Medicine	Saint Louis	Missouri	United States	63110-1093
11	John Theurer Cancer Center at Hackensack UMC	Hackensack	New Jersey	United States	07601
12	Weill Cornell Medical College	New York	New York	United States	10021
13	Mount Sinai School of Medicine	New York	New York	United States	10029
14	Gabrail Cancer Center Research	Canton	Ohio	United States	44718
15	The Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
16	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
17	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203-1632
18	Texas Oncology Cancer Center	Austin	Texas	United States	78731
19	The University of Texas, MD Anderson Cancer Center	Houston	Texas	United States	77030
20	Northwest Cancer Center	Houston	Texas	United States	77090
21	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
22	University of Toronto, Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
23	Jewish General Hospital	Montreal	Quebec	Canada	H3t 1E2

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

• Study Protocol - Mar 25, 2011
• Statistical Analysis Plan - Jul 28, 2017

More Information

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT00884312
• Other Study ID Numbers: PX-171-010; 20130394
• First Posted: Apr 20, 2009
• Last Update Posted: May 14, 2018
• Last Verified: Apr 1, 2018

• Keywords provided by Amgen: Multiple myeloma; proteasome; Hematological; carfilzomib; PR-171
• Additional relevant MeSH terms: Multiple Myeloma

Study Results

Participant Flow

Recruitment Details	This study was conducted at 23 centers in the United States and Canada from April 2009 to May 2017.

Arm/Group Title	Solid Tumors	Multiple Myeloma
Arm/Group Description	Participants with solid tumors received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.	Participants with multiple myeloma received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.
Period Title: Overall Study
STARTED	9	92
Received Treatment	9	91
COMPLETED	7	67
NOT COMPLETED	2	25

Baseline Characteristics

Arm/Group Title	Solid Tumors	Multiple Myeloma	Total
Arm/Group Description	Participants with solid tumors received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.	Participants with multiple myeloma received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.	Total of all reporting groups
Overall Participants	9	91	100
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.2 (12.75)	63.2 (9.82)	63.0 (10.05)
Age, Customized (Count of Participants)
< 65 years	5 55.6%	47 51.6%	52 52%
≥ 65 years	4 44.4%	44 48.4%	48 48%
Sex: Female, Male (Count of Participants)
Female	6 66.7%	38 41.8%	44 44%
Male	3 33.3%	53 58.2%	56 56%
Race/Ethnicity, Customized (Count of Participants)
White	9 100%	71 78%	80 80%
Black	0 0%	11 12.1%	11 11%
Hispanic	0 0%	5 5.5%	5 5%
Asian/Pacific Islander	0 0%	4 4.4%	4 4%
Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants)
0 (Fully active)	6 66.7%	39 42.9%	45 45%
1 (Restricted but ambulatory)	3 33.3%	42 46.2%	45 45%
2 (Ambulatory but unable to work)	0 0%	10 11%	10 10%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Peripheral Neuropathy
Description	Participants with peripheral neuropathy or peripheral neuropathy-related adverse events, including hypoaesthesia, paraesthesia, dysaesthesia, and neuropathic pain.
Time Frame	From first dose of study drug to 30 days after the last dose; median duration of treatment was 14 weeks for participants with solid tumors and 44 weeks for participants with multiple myeloma.

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of carfilzomib after enrollment in PX-171-010.

Arm/Group Title	Solid Tumors	Multiple Myeloma
Arm/Group Description	Participants with solid tumors received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.	Participants with multiple myeloma received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.
Measure Participants	9	91
Number [participants]	1 11.1%	15 16.5%

2. Primary Outcome

Title	Number of Participants With Adverse Events
Description	Adverse events (AEs) were assigned a severity grade using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) grading scale version 3.0. Per protocol, adverse events were collected if they led to dose modification or dose discontinuation, were grade ≥ 3 or serious, or were events of peripheral neuropathy (any grade). A serious AE is one that met one or more of the following criteria: Death Life threatening Required inpatient hospitalization or prolongation of an existing hospitalization Resulted in persistent or significant disability/incapacity A congenital anomaly/birth defect in the offspring of an exposed subject Important medical events that, based upon appropriate medical judgment, jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes above.
Time Frame	From first dose of study drug to 30 days after the last dose; median duration of treatment was 14 weeks for participants with solid tumors and 44 weeks for participants with multiple myeloma.

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of carfilzomib after enrollment in PX-171-010.

Arm/Group Title	Solid Tumors	Multiple Myeloma
Arm/Group Description	Participants with solid tumors received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.	Participants with multiple myeloma received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.
Measure Participants	9	91
Any adverse event	7 77.8%	84 92.3%
Adverse event ≥ grade 3	5 55.6%	66 72.5%
Serious adverse events	5 55.6%	57 62.6%
Fatal adverse events	1 11.1%	7 7.7%
AE leading to discontinuation of carfilzomib	5 55.6%	20 22%

3. Secondary Outcome

Title	Overall Survival
Description	Since participants were only followed up to 30 days after administration of last dose of study drug per protocol, Kaplan-Meier estimates of overall survival were not calculated. The number of participants who died within 30 days after administration of last dose of study drug is reported.
Time Frame	From first dose of study drug to 30 days after the last dose; median duration of treatment was 14 weeks for participants with solid tumors and 44 weeks for participants with multiple myeloma.

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of carfilzomib after enrollment in PX-171-010.

Arm/Group Title	Solid Tumors	Multiple Myeloma
Arm/Group Description	Participants with solid tumors received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.	Participants with multiple myeloma received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.
Measure Participants	9	91
Number [participants]	1 11.1%	7 7.7%

4. Secondary Outcome

Title	Progression-free Survival
Description	Progression-free survival (PFS) was defined as the time between the start of treatment and first evidence of documented disease progression or death (due to any cause), whichever occurred first. Disease progression was determined by the local investigator for regimens with the same baseline using the International Uniform Response Criteria (IMWG-URC) for participants with multiple myeloma and Response Evaluation Criteria in Solid Tumors (RECIST) criteria for solid tumor participants. PFS was re-calculated whenever the baseline was reset due to addition of new anti-cancer therapy or increase of carfilzomib dose/frequency.
Time Frame	From first dose of study drug in study PX-171-010 to 30 days after the last dose; median duration of treatment was 14 weeks for participants with solid tumors and 44 weeks for participants with multiple myeloma.

Outcome Measure Data

Analysis Population Description

Enrolled participants excluding those with no postbaseline endpoint data subsequent to at least 1 dose of the study drug on the PX-171-010 protocol and participants who lacked baseline data for those analyses that required baseline data. Only participants with regimens that continued from the initial study without baseline being reset are included.

Arm/Group Title	Solid Tumors	Multiple Myeloma
Arm/Group Description	Participants with solid tumors received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.	Participants with multiple myeloma received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.
Measure Participants	6	58
Median (95% Confidence Interval) [months]	41.9	19.6

5. Secondary Outcome

Title	Time to Progression
Description	Time to progression (TTP) was defined as the time between start of treatment to the first documentation of disease progression. TTP was re-calculated whenever the baseline was reset due to addition of new anti-cancer therapy or increase of carfilzomib dose/frequency.
Time Frame	From first dose of study drug in study PX-171-010 to 30 days after the last dose; median duration of treatment was 14 weeks for participants with solid tumors and 44 weeks for participants with multiple myeloma.

Outcome Measure Data

Analysis Population Description

Enrolled participants excluding those with no postbaseline endpoint data subsequent to at least 1 dose of the study drug on the PX-171-010 protocol and participants who lacked baseline data for those analyses that required baseline data Only participants with regimens that continued from the initial study without baseline being reset are included.

Arm/Group Title	Solid Tumors	Multiple Myeloma
Arm/Group Description	Participants with solid tumors received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.	Participants with multiple myeloma received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.
Measure Participants	6	58
Median (95% Confidence Interval) [months]	NA	19.6

Adverse Events

Time Frame	From first dose of study drug to 30 days after the last dose; median duration of treatment was 14 weeks for participants with solid tumors and 44 weeks for participants with multiple myeloma.
Adverse Event Reporting Description	The protocol indicated that AEs leading to dose modification, dose discontinuation, CTCAE grade 3+, serious AEs and all-grade peripheral neuropathy AEs were collected in the study. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Arm/Group Title	Solid Tumors		Multiple Myeloma
Arm/Group Description	Participants with solid tumors received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.		Participants with multiple myeloma received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib.
All Cause Mortality
	Solid Tumors		Multiple Myeloma
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/9 (11.1%)		7/91 (7.7%)
Serious Adverse Events
	Solid Tumors		Multiple Myeloma
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/9 (55.6%)		57/91 (62.6%)
Blood and lymphatic system disorders
Anaemia	0/9 (0%)		1/91 (1.1%)
Febrile neutropenia	0/9 (0%)		5/91 (5.5%)
Haemolytic uraemic syndrome	0/9 (0%)		1/91 (1.1%)
Cardiac disorders
Acute myocardial infarction	0/9 (0%)		1/91 (1.1%)
Atrial fibrillation	0/9 (0%)		2/91 (2.2%)
Cardiac failure congestive	0/9 (0%)		3/91 (3.3%)
Cardiac tamponade	1/9 (11.1%)		0/91 (0%)
Cardiomyopathy	1/9 (11.1%)		0/91 (0%)
Coronary artery occlusion	0/9 (0%)		1/91 (1.1%)
Myocardial infarction	0/9 (0%)		3/91 (3.3%)
Tachycardia	0/9 (0%)		1/91 (1.1%)
Ear and labyrinth disorders
Vertigo	0/9 (0%)		1/91 (1.1%)
Gastrointestinal disorders
Colitis	0/9 (0%)		1/91 (1.1%)
Diarrhoea	0/9 (0%)		3/91 (3.3%)
Gastrointestinal haemorrhage	0/9 (0%)		1/91 (1.1%)
Nausea	0/9 (0%)		2/91 (2.2%)
General disorders
Asthenia	0/9 (0%)		1/91 (1.1%)
Chest pain	0/9 (0%)		1/91 (1.1%)
Disease progression	0/9 (0%)		2/91 (2.2%)
Infusion related reaction	0/9 (0%)		1/91 (1.1%)
Non-cardiac chest pain	0/9 (0%)		1/91 (1.1%)
Pain	0/9 (0%)		2/91 (2.2%)
Pyrexia	0/9 (0%)		2/91 (2.2%)
Infections and infestations
Bronchiolitis	0/9 (0%)		1/91 (1.1%)
Bronchitis	0/9 (0%)		3/91 (3.3%)
Catheter sepsis	0/9 (0%)		1/91 (1.1%)
Cellulitis	0/9 (0%)		3/91 (3.3%)
Chronic sinusitis	0/9 (0%)		1/91 (1.1%)
Clostridial infection	0/9 (0%)		1/91 (1.1%)
Endocarditis bacterial	0/9 (0%)		1/91 (1.1%)
Gastroenteritis viral	0/9 (0%)		1/91 (1.1%)
Haemophilus sepsis	0/9 (0%)		1/91 (1.1%)
Herpes zoster ophthalmic	1/9 (11.1%)		0/91 (0%)
Infection	1/9 (11.1%)		0/91 (0%)
Influenza	0/9 (0%)		6/91 (6.6%)
Intraspinal abscess	0/9 (0%)		1/91 (1.1%)
Klebsiella bacteraemia	0/9 (0%)		1/91 (1.1%)
Lobar pneumonia	0/9 (0%)		1/91 (1.1%)
Lung infection	0/9 (0%)		1/91 (1.1%)
Neutropenic sepsis	0/9 (0%)		1/91 (1.1%)
Otitis media	0/9 (0%)		1/91 (1.1%)
Pneumonia	1/9 (11.1%)		10/91 (11%)
Pneumonia pneumococcal	0/9 (0%)		1/91 (1.1%)
Pneumonia respiratory syncytial viral	0/9 (0%)		2/91 (2.2%)
Pneumonia viral	0/9 (0%)		1/91 (1.1%)
Respiratory syncytial virus infection	0/9 (0%)		1/91 (1.1%)
Sepsis	1/9 (11.1%)		3/91 (3.3%)
Sinusitis	0/9 (0%)		2/91 (2.2%)
Staphylococcal bacteraemia	0/9 (0%)		1/91 (1.1%)
Staphylococcal sepsis	0/9 (0%)		1/91 (1.1%)
Streptococcal infection	0/9 (0%)		1/91 (1.1%)
Tooth infection	0/9 (0%)		1/91 (1.1%)
Upper respiratory tract infection	0/9 (0%)		1/91 (1.1%)
Urinary tract infection pseudomonal	0/9 (0%)		1/91 (1.1%)
Injury, poisoning and procedural complications
Cervical vertebral fracture	0/9 (0%)		1/91 (1.1%)
Fall	0/9 (0%)		1/91 (1.1%)
Femoral neck fracture	0/9 (0%)		1/91 (1.1%)
Femur fracture	0/9 (0%)		2/91 (2.2%)
Fracture	0/9 (0%)		1/91 (1.1%)
Hip fracture	0/9 (0%)		1/91 (1.1%)
Lumbar vertebral fracture	0/9 (0%)		1/91 (1.1%)
Investigations
Transaminases increased	0/9 (0%)		1/91 (1.1%)
Metabolism and nutrition disorders
Dehydration	0/9 (0%)		2/91 (2.2%)
Hypercalcaemia	0/9 (0%)		1/91 (1.1%)
Hypoglycaemia	0/9 (0%)		1/91 (1.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/9 (11.1%)		1/91 (1.1%)
Back pain	0/9 (0%)		3/91 (3.3%)
Osteolysis	0/9 (0%)		1/91 (1.1%)
Pain in extremity	0/9 (0%)		1/91 (1.1%)
Pathological fracture	0/9 (0%)		2/91 (2.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma	0/9 (0%)		1/91 (1.1%)
Renal cell carcinoma stage unspecified	0/9 (0%)		1/91 (1.1%)
Nervous system disorders
Cerebrovascular accident	0/9 (0%)		2/91 (2.2%)
Dizziness	0/9 (0%)		1/91 (1.1%)
Spinal cord compression	0/9 (0%)		1/91 (1.1%)
Syncope	0/9 (0%)		1/91 (1.1%)
Psychiatric disorders
Delirium	0/9 (0%)		1/91 (1.1%)
Mental status changes	0/9 (0%)		1/91 (1.1%)
Renal and urinary disorders
Haematuria	0/9 (0%)		1/91 (1.1%)
Renal failure acute	1/9 (11.1%)		4/91 (4.4%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/9 (0%)		1/91 (1.1%)
Chronic obstructive pulmonary disease	0/9 (0%)		1/91 (1.1%)
Cough	0/9 (0%)		1/91 (1.1%)
Dyspnoea	0/9 (0%)		4/91 (4.4%)
Dyspnoea exertional	0/9 (0%)		1/91 (1.1%)
Pleural effusion	0/9 (0%)		1/91 (1.1%)
Pneumonitis	0/9 (0%)		1/91 (1.1%)
Pulmonary embolism	0/9 (0%)		1/91 (1.1%)
Pulmonary haemorrhage	1/9 (11.1%)		0/91 (0%)
Pulmonary hypertension	0/9 (0%)		2/91 (2.2%)
Respiratory failure	0/9 (0%)		2/91 (2.2%)
Other (Not Including Serious) Adverse Events
	Solid Tumors		Multiple Myeloma
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/9 (66.7%)		69/91 (75.8%)
Blood and lymphatic system disorders
Anaemia	0/9 (0%)		18/91 (19.8%)
Neutropenia	0/9 (0%)		19/91 (20.9%)
Thrombocytopenia	0/9 (0%)		16/91 (17.6%)
Gastrointestinal disorders
Abdominal discomfort	1/9 (11.1%)		0/91 (0%)
Abdominal distension	1/9 (11.1%)		0/91 (0%)
Abdominal pain	1/9 (11.1%)		0/91 (0%)
Ascites	1/9 (11.1%)		0/91 (0%)
Diarrhoea	0/9 (0%)		12/91 (13.2%)
Nausea	2/9 (22.2%)		11/91 (12.1%)
Vomiting	3/9 (33.3%)		5/91 (5.5%)
General disorders
Asthenia	1/9 (11.1%)		1/91 (1.1%)
Chills	1/9 (11.1%)		1/91 (1.1%)
Fatigue	3/9 (33.3%)		16/91 (17.6%)
Infusion site pain	1/9 (11.1%)		1/91 (1.1%)
Pyrexia	2/9 (22.2%)		4/91 (4.4%)
Sensation of pressure	1/9 (11.1%)		0/91 (0%)
Immune system disorders
Seasonal allergy	1/9 (11.1%)		0/91 (0%)
Infections and infestations
Bronchitis	1/9 (11.1%)		1/91 (1.1%)
Herpes simplex	1/9 (11.1%)		0/91 (0%)
Nasopharyngitis	2/9 (22.2%)		1/91 (1.1%)
Pneumonia	0/9 (0%)		6/91 (6.6%)
Sinusitis	1/9 (11.1%)		3/91 (3.3%)
Upper respiratory tract infection	1/9 (11.1%)		21/91 (23.1%)
Urinary tract infection	1/9 (11.1%)		1/91 (1.1%)
Investigations
Blood creatinine increased	0/9 (0%)		5/91 (5.5%)
Metabolism and nutrition disorders
Dehydration	1/9 (11.1%)		1/91 (1.1%)
Hyperglycaemia	0/9 (0%)		5/91 (5.5%)
Hypophosphataemia	0/9 (0%)		6/91 (6.6%)
Musculoskeletal and connective tissue disorders
Back pain	0/9 (0%)		5/91 (5.5%)
Pain in extremity	1/9 (11.1%)		7/91 (7.7%)
Nervous system disorders
Dysarthria	1/9 (11.1%)		0/91 (0%)
Facial palsy	1/9 (11.1%)		0/91 (0%)
Headache	1/9 (11.1%)		0/91 (0%)
Hypoaesthesia	1/9 (11.1%)		1/91 (1.1%)
Neuropathy peripheral	0/9 (0%)		10/91 (11%)
Transient ischaemic attack	1/9 (11.1%)		0/91 (0%)
Psychiatric disorders
Confusional state	1/9 (11.1%)		1/91 (1.1%)
Insomnia	1/9 (11.1%)		3/91 (3.3%)
Renal and urinary disorders
Dysuria	1/9 (11.1%)		0/91 (0%)
Urinary incontinence	1/9 (11.1%)		1/91 (1.1%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/9 (22.2%)		14/91 (15.4%)
Pharyngolaryngeal pain	1/9 (11.1%)		1/91 (1.1%)
Rhinorrhoea	1/9 (11.1%)		1/91 (1.1%)
Sinus congestion	1/9 (11.1%)		1/91 (1.1%)
Wheezing	1/9 (11.1%)		2/91 (2.2%)
Skin and subcutaneous tissue disorders
Night sweats	1/9 (11.1%)		2/91 (2.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.