Study of DOXIL/CAELYX (Pegylated Liposomal Doxorubicin) and VELCADE (Bortezomib) or VELCADE Monotherapy for the Treatment of Relapsed Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT00103506

Recruitment Status : Completed

First Posted : February 10, 2005

Results First Posted : May 25, 2015

Last Update Posted : October 19, 2015

Sponsor:

Information provided by (Responsible Party):

Janssen Research & Development, LLC

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Multiple Myeloma
Interventions	Drug: Bortezomib (VELCADE) Drug: Doxorubicin hydrochloride (DOXIL/CAELYX)
Enrollment	646

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Velcade (Bortezomib) Monotherapy	Doxil/Caelyx Plus Velcade (Bortezomib)
Arm/Group Description	Velcade (bortezomib) 1.3 milligram/...	Velcade (bortezomib) 1.3 mg/m^2 by ...
Arm/Group Description	Velcade (bortezomib) 1.3 milligram/meter per square (mg/m^2) by rapid (bolus) intravenous (IV) administration given on Day 1, 4, 8, and 11 of each 21-day cycle for up to 8 cycles.	Velcade (bortezomib) 1.3 mg/m^2 by rapid (bolus) IV administration given on Day 1, 4, 8, and 11 of each 21-day cycle for up to 8 cycles. Doxorubicin hydrochloride (DOXIL/CAELYX) 30 mg/m^2 by IV infusion will be given on Day 4 of every 21-day cycle after the administration of VELCADE (bortezomib) up to 8 cycles.
Period Title: Overall Study
Started	322	324
Completed	0	0
Not Completed	322	324
Reason Not Completed
Study closed by sponsor	34	37
Death	257	253
Lost to Follow-up	13	13
Withdrawal by Subject	18	21

Baseline Characteristics

Arm/Group Title		Velcade (Bortezomib) Monotherapy	Doxil/Caelyx Plus Velcade (Bortezomib)	Total
Arm/Group Description		Velcade (bortezomib) 1.3 milligram/...	Velcade (bortezomib) 1.3 mg/m^2 by ...	Total of all reporting groups
Arm/Group Description		Velcade (bortezomib) 1.3 milligram/meter per square (mg/m^2) by rapid (bolus) intravenous (IV) administration given on Day 1, 4, 8, and 11 of each 21-day cycle for up to 8 cycles.	Velcade (bortezomib) 1.3 mg/m^2 by rapid (bolus) IV administration given on Day 1, 4, 8, and 11 of each 21-day cycle for up to 8 cycles. Doxorubicin hydrochloride (DOXIL/CAELYX) 30 mg/m^2 by IV infusion will be given on Day 4 of every 21-day cycle after the administration of VELCADE (bortezomib) up to 8 cycles.	Total of all reporting groups
Overall Number of Baseline Participants		322	324	646
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	322 participants	324 participants	646 participants
		61.5 (9.56)	61.4 (9.61)	61.4 (9.58)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	322 participants	324 participants	646 participants
	Female	148 46.0%	135 41.7%	283 43.8%
	Male	174 54.0%	189 58.3%	363 56.2%
Region of Enrollment Measure Type: Number Unit of measure: Participants	Number Analyzed	322 participants	324 participants	646 participants
ARGENTINA		6	9	15
AUSTRALIA		31	31	62
AUSTRIA		12	6	18
BELGIUM-LUXEMBURG		6	14	20
CANADA		20	23	43
CZECH REPUBLIC		14	22	36
FRANCE		21	28	49
GREAT BRITAIN		8	7	15
ISRAEL		25	21	46
ITALY		17	11	28
NETHERLANDS		29	32	61
POLAND		35	17	52
PORTUGAL		6	14	20
RUSSIA		38	34	72
SINGAPORE		3	2	5
SOUTH AFRICA		13	15	28
SPAIN		20	15	35
UNITED STATES OF AMERICA		18	23	41

Outcome Measures

1.Primary Outcome


Title	Time to Progression (TTP)
Description	Median time to progression of disease is assessed according to Interna...
Description	Median time to progression of disease is assessed according to International Myeloma Working Group (IMWG) criteria or death from any cause. IMWG criteria: increase of >=25% from lowest level in Serum M-component or (the absolute increase must be >=0.5 gram per deciliter [g/dL]); Urine M component or (the absolute increase must be >=200 milligram per 24 hour. Only in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain levels. The absolute increase >10 mg/dL. Bone marrow plasma cell percentage >=10%. Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing. Development of hypercalcemia. Participants who died or dropped out due to any reason without progression will be censored with the day of death or drop-out, respectively and who are alive at the end of the study without any progression was censored with the last available date.
Time Frame	Up to 1 year and 4 months (From date of first participant randomization [20 December 2004] up to interim analysis cut-off date [28 April 2006])

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) included all the randomized participants.


Arm/Group Title	Velcade (Bortezomib) Monotherapy	Doxil/Caelyx Plus Velcade (Bortezomib)
Arm/Group Description:	Velcade (bortezomib) 1.3 milligram/...	Velcade (bortezomib) 1.3 mg/m^2 by ...
Arm/Group Description:	Velcade (bortezomib) 1.3 milligram/meter per square (mg/m^2) by rapid (bolus) intravenous (IV) administration given on Day 1, 4, 8, and 11 of each 21-day cycle for up to 8 cycles.	Velcade (bortezomib) 1.3 mg/m^2 by rapid (bolus) IV administration given on Day 1, 4, 8, and 11 of each 21-day cycle for up to 8 cycles. Doxorubicin hydrochloride (DOXIL/CAELYX) 30 mg/m^2 by IV infusion will be given on Day 4 of every 21-day cycle after the administration of VELCADE (bortezomib) up to 8 cycles.
Overall Number of Participants Analyzed	322	324
Median (95% Confidence Interval) Unit of Measure: Months
	6.5 (5.6 to 7.1)	9.3 (8.2 to 11.1)

2.Secondary Outcome


Title	Overall Survival
Description	The OS is defined as the time from the date of first dose of study dru...
Description	The OS is defined as the time from the date of first dose of study drug to date of death from any cause. If the participant is alive or the vital status is unknown, the participant will be censored at the date the participant will be last known to be alive.
Time Frame	Up to 9 years and 5 months (From date of first participant randomization [20 December 2004] to cut-off date for final survival analysis (16 May 2014)

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Velcade (Bortezomib) Monotherapy	Doxil/Caelyx Plus Velcade (Bortezomib)
Arm/Group Description:	Velcade (bortezomib) 1.3 milligram/...	Velcade (bortezomib) 1.3 mg/m^2 by ...
Arm/Group Description:	Velcade (bortezomib) 1.3 milligram/meter per square (mg/m^2) by rapid (bolus) intravenous (IV) administration given on Day 1, 4, 8, and 11 of each 21-day cycle for up to 8 cycles.	Velcade (bortezomib) 1.3 mg/m^2 by rapid (bolus) IV administration given on Day 1, 4, 8, and 11 of each 21-day cycle for up to 8 cycles. Doxorubicin hydrochloride (DOXIL/CAELYX) 30 mg/m^2 by IV infusion will be given on Day 4 of every 21-day cycle after the administration of VELCADE (bortezomib) up to 8 cycles.
Overall Number of Participants Analyzed	322	324
Median (95% Confidence Interval) Unit of Measure: months
	30.8 (25.2 to 36.5)	33.0 (28.9 to 37.1)

3.Secondary Outcome


Title	Number of Participants With Serious Adverse Events (SAEs)
Description	A serious adverse event (SAE) was an AE resulting in any of the follow...
Description	A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time Frame	Up to 1 year and 11 months (From date of first participant randomization [20 December 2004] to cut-off date for safety update (28 November 2006)

Outcome Measure Data

Analysis Population Description

Safety population included all the participants who received at least one dose of study drug. Here ‘N’ (number of participants analyzed) signifies those participants who were evaluable for this measure.


Arm/Group Title	Velcade (Bortezomib) Monotherapy	Doxil/Caelyx Plus Velcade (Bortezomib)
Arm/Group Description:	Velcade (bortezomib) 1.3 milligram/...	Velcade (bortezomib) 1.3 mg/m^2 by ...
Arm/Group Description:	Velcade (bortezomib) 1.3 milligram/meter per square (mg/m^2) by rapid (bolus) intravenous (IV) administration given on Day 1, 4, 8, and 11 of each 21-day cycle for up to 8 cycles.	Velcade (bortezomib) 1.3 mg/m^2 by rapid (bolus) IV administration given on Day 1, 4, 8, and 11 of each 21-day cycle for up to 8 cycles. Doxorubicin hydrochloride (DOXIL/CAELYX) 30 mg/m^2 by IV infusion will be given on Day 4 of every 21-day cycle after the administration of VELCADE (bortezomib) up to 8 cycles.
Overall Number of Participants Analyzed	318	318
Measure Type: Number Unit of Measure: Participants
	105	120

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	Safety population included all the participants who received at least one dose of study drug.

Arm/Group Title	Velcade (Bortezomib) Monotherapy	Doxil/Caelyx Plus Velcade (Bortezomib)
Arm/Group Description	Velcade (bortezomib) 1.3 milligram/...	Velcade (bortezomib) 1.3 mg/m^2 by ...
Arm/Group Description	Velcade (bortezomib) 1.3 milligram/meter per square (mg/m^2) by rapid (bolus) intravenous (IV) administration given on Day 1, 4, 8, and 11 of each 21-day cycle for up to 8 cycles.	Velcade (bortezomib) 1.3 mg/m^2 by rapid (bolus) IV administration given on Day 1, 4, 8, and 11 of each 21-day cycle for up to 8 cycles. Doxorubicin hydrochloride (DOXIL/CAELYX) 30 mg/m^2 by IV infusion will be given on Day 4 of every 21-day cycle after the administration of VELCADE (bortezomib) up to 8 cycles.
All-Cause Mortality
	Velcade (Bortezomib) Monotherapy	Doxil/Caelyx Plus Velcade (Bortezomib)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events Serious Adverse Events
	Velcade (Bortezomib) Monotherapy	Doxil/Caelyx Plus Velcade (Bortezomib)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	105/318 (33.02%)	120/318 (37.74%)
Blood and lymphatic system disorders
Anaemia ^* 1	4/318 (1.26%)	3/318 (0.94%)
Febrile Neutropenia ^* 1	2/318 (0.63%)	5/318 (1.57%)
Leukopenia ^* 1	0/318 (0.00%)	1/318 (0.31%)
Neutropenia ^* 1	0/318 (0.00%)	2/318 (0.63%)
Pancytopenia ^* 1	0/318 (0.00%)	2/318 (0.63%)
Thrombocytopenia ^* 1	0/318 (0.00%)	9/318 (2.83%)
Cardiac disorders
Acute Myocardial Infarction ^* 1	0/318 (0.00%)	1/318 (0.31%)
Angina Pectoris ^* 1	1/318 (0.31%)	0/318 (0.00%)
Angina Unstable ^* 1	1/318 (0.31%)	0/318 (0.00%)
Arrhythmia ^* 1	1/318 (0.31%)	0/318 (0.00%)
Atrial Fibrillation ^* 1	2/318 (0.63%)	0/318 (0.00%)
Atrial Flutter ^* 1	0/318 (0.00%)	1/318 (0.31%)
Cardiac Arrest ^* 1	0/318 (0.00%)	1/318 (0.31%)
Cardiac Failure ^* 1	2/318 (0.63%)	0/318 (0.00%)
Cardiac Failure Chronic ^* 1	0/318 (0.00%)	1/318 (0.31%)
Cardiac Failure Congestive ^* 1	2/318 (0.63%)	2/318 (0.63%)
Cardio-Respiratory Arrest ^* 1	1/318 (0.31%)	0/318 (0.00%)
Myocardial Infarction ^* 1	1/318 (0.31%)	2/318 (0.63%)
Nodal Arrhythmia ^* 1	0/318 (0.00%)	1/318 (0.31%)
Right Ventricular Failure ^* 1	1/318 (0.31%)	1/318 (0.31%)
Tachyarrhythmia ^* 1	0/318 (0.00%)	1/318 (0.31%)
Ear and labyrinth disorders
Deafness ^* 1	0/318 (0.00%)	1/318 (0.31%)
Vertigo ^* 1	3/318 (0.94%)	0/318 (0.00%)
Endocrine disorders
Adrenal Insufficiency ^* 1	0/318 (0.00%)	1/318 (0.31%)
Hypercorticoidism ^* 1	0/318 (0.00%)	1/318 (0.31%)
Inappropriate Antidiuretic Hormone Secretion ^* 1	1/318 (0.31%)	0/318 (0.00%)
Eye disorders
Cataract ^* 1	0/318 (0.00%)	1/318 (0.31%)
Corneal Erosion ^* 1	0/318 (0.00%)	1/318 (0.31%)
Diplopia ^* 1	1/318 (0.31%)	0/318 (0.00%)
Retinal Vein Thrombosis ^* 1	1/318 (0.31%)	0/318 (0.00%)
Gastrointestinal disorders
Abdominal Pain ^* 1	2/318 (0.63%)	2/318 (0.63%)
Diarrhoea ^* 1	6/318 (1.89%)	7/318 (2.20%)
Dyspepsia ^* 1	0/318 (0.00%)	1/318 (0.31%)
Dysphagia ^* 1	0/318 (0.00%)	2/318 (0.63%)
Faecaloma ^* 1	0/318 (0.00%)	1/318 (0.31%)
Flatulence ^* 1	1/318 (0.31%)	0/318 (0.00%)
Gastric Ulcer ^* 1	0/318 (0.00%)	2/318 (0.63%)
Gastroduodenal Haemorrhage ^* 1	0/318 (0.00%)	1/318 (0.31%)
Gastrointestinal Haemorrhage ^* 1	1/318 (0.31%)	3/318 (0.94%)
Gastrooesophageal Reflux Disease ^* 1	0/318 (0.00%)	1/318 (0.31%)
Haematemesis ^* 1	2/318 (0.63%)	2/318 (0.63%)
Ileus ^* 1	0/318 (0.00%)	1/318 (0.31%)
Ileus Paralytic ^* 1	1/318 (0.31%)	1/318 (0.31%)
Large Intestine Perforation ^* 1	0/318 (0.00%)	1/318 (0.31%)
Mallory-Weiss Syndrome ^* 1	0/318 (0.00%)	2/318 (0.63%)
Nausea ^* 1	3/318 (0.94%)	7/318 (2.20%)
Rectal Haemorrhage ^* 1	0/318 (0.00%)	1/318 (0.31%)
Rectal Prolapse ^* 1	1/318 (0.31%)	0/318 (0.00%)
Small Intestinal Obstruction ^* 1	1/318 (0.31%)	1/318 (0.31%)
Stomatitis ^* 1	0/318 (0.00%)	1/318 (0.31%)
Upper Gastrointestinal Haemorrhage ^* 1	0/318 (0.00%)	2/318 (0.63%)
Vomiting ^* 1	2/318 (0.63%)	13/318 (4.09%)
General disorders
Asthenia ^* 1	1/318 (0.31%)	2/318 (0.63%)
Catheter Related Complication ^* 1	1/318 (0.31%)	0/318 (0.00%)
Chest Pain ^* 1	3/318 (0.94%)	0/318 (0.00%)
Chills ^* 1	1/318 (0.31%)	0/318 (0.00%)
Death ^* 1	1/318 (0.31%)	0/318 (0.00%)
Fatigue ^* 1	0/318 (0.00%)	3/318 (0.94%)
General Physical Health Deterioration ^* 1	0/318 (0.00%)	1/318 (0.31%)
Hyperthermia ^* 1	1/318 (0.31%)	0/318 (0.00%)
Influenza Like Illness ^* 1	0/318 (0.00%)	1/318 (0.31%)
Multi-Organ Failure ^* 1	0/318 (0.00%)	1/318 (0.31%)
Oedema Peripheral ^* 1	1/318 (0.31%)	0/318 (0.00%)
Pain ^* 1	0/318 (0.00%)	1/318 (0.31%)
Pyrexia ^* 1	8/318 (2.52%)	15/318 (4.72%)
Sudden Cardiac Death ^* 1	1/318 (0.31%)	0/318 (0.00%)
Sudden Death ^* 1	0/318 (0.00%)	1/318 (0.31%)
Immune system disorders
Hypersensitivity ^* 1	0/318 (0.00%)	1/318 (0.31%)
Infections and infestations
Abdominal Infection ^* 1	0/318 (0.00%)	1/318 (0.31%)
Bacterial Sepsis ^* 1	1/318 (0.31%)	0/318 (0.00%)
Bronchitis ^* 1	1/318 (0.31%)	0/318 (0.00%)
Bronchitis Acute ^* 1	2/318 (0.63%)	0/318 (0.00%)
Bronchitis Chronic ^* 1	2/318 (0.63%)	0/318 (0.00%)
Bronchopneumonia ^* 1	1/318 (0.31%)	3/318 (0.94%)
Candidiasis ^* 1	0/318 (0.00%)	1/318 (0.31%)
Catheter Related Infection ^* 1	0/318 (0.00%)	2/318 (0.63%)
Cellulitis ^* 1	1/318 (0.31%)	1/318 (0.31%)
Diarrhoea Infectious ^* 1	1/318 (0.31%)	0/318 (0.00%)
Ear Infection ^* 1	0/318 (0.00%)	1/318 (0.31%)
Furuncle ^* 1	0/318 (0.00%)	1/318 (0.31%)
Gastroenteritis ^* 1	3/318 (0.94%)	1/318 (0.31%)
Genitourinary Tract Infection ^* 1	1/318 (0.31%)	0/318 (0.00%)
Herpes Zoster ^* 1	3/318 (0.94%)	5/318 (1.57%)
Herpes Zoster Disseminated ^* 1	1/318 (0.31%)	1/318 (0.31%)
Infection ^* 1	1/318 (0.31%)	1/318 (0.31%)
Klebsiella Sepsis ^* 1	1/318 (0.31%)	0/318 (0.00%)
Laryngitis ^* 1	1/318 (0.31%)	0/318 (0.00%)
Lobar Pneumonia ^* 1	1/318 (0.31%)	0/318 (0.00%)
Lower Respiratory Tract Infection ^* 1	3/318 (0.94%)	3/318 (0.94%)
Meningitis Bacterial ^* 1	1/318 (0.31%)	0/318 (0.00%)
Neutropenic Sepsis ^* 1	0/318 (0.00%)	1/318 (0.31%)
Opportunistic Infection ^* 1	0/318 (0.00%)	1/318 (0.31%)
Orchitis ^* 1	0/318 (0.00%)	1/318 (0.31%)
Osteomyelitis ^* 1	0/318 (0.00%)	1/318 (0.31%)
Pneumococcal Bacteraemia ^* 1	0/318 (0.00%)	1/318 (0.31%)
Pneumococcal Sepsis ^* 1	1/318 (0.31%)	2/318 (0.63%)
Pneumocystis JiroveCI Pneumonia ^* 1	0/318 (0.00%)	1/318 (0.31%)
Pneumonia ^* 1	20/318 (6.29%)	16/318 (5.03%)
Pneumonia Aspergillus ^* 1	1/318 (0.31%)	0/318 (0.00%)
Pneumonia Legionella ^* 1	0/318 (0.00%)	1/318 (0.31%)
Pneumonia Pneumococcal ^* 1	0/318 (0.00%)	1/318 (0.31%)
Pseudomonas Infection ^* 1	0/318 (0.00%)	2/318 (0.63%)
Respiratory Tract Infection ^* 1	2/318 (0.63%)	3/318 (0.94%)
Respiratory Tract Infection Bacterial ^* 1	0/318 (0.00%)	1/318 (0.31%)
Sepsis ^* 1	0/318 (0.00%)	1/318 (0.31%)
Septic Embolus ^* 1	0/318 (0.00%)	1/318 (0.31%)
Septic Shock ^* 1	1/318 (0.31%)	3/318 (0.94%)
Sinusitis ^* 1	1/318 (0.31%)	0/318 (0.00%)
Skin Infection ^* 1	1/318 (0.31%)	0/318 (0.00%)
Staphylococcal Sepsis ^* 1	0/318 (0.00%)	2/318 (0.63%)
Upper Respiratory Tract Infection ^* 1	2/318 (0.63%)	4/318 (1.26%)
Urinary Tract Infection ^* 1	2/318 (0.63%)	0/318 (0.00%)
Urosepsis ^* 1	1/318 (0.31%)	0/318 (0.00%)
Injury, poisoning and procedural complications
Drug Toxicity ^* 1	0/318 (0.00%)	1/318 (0.31%)
Fall ^* 1	1/318 (0.31%)	1/318 (0.31%)
Skeletal Injury ^* 1	0/318 (0.00%)	1/318 (0.31%)
Spinal Compression Fracture ^* 1	0/318 (0.00%)	1/318 (0.31%)
Thoracic Vertebral Fracture ^* 1	1/318 (0.31%)	0/318 (0.00%)
Investigations
Blood Creatinine Increased ^* 1	2/318 (0.63%)	3/318 (0.94%)
Blood Glucose Increased ^* 1	0/318 (0.00%)	1/318 (0.31%)
Ejection Fraction Decreased ^* 1	0/318 (0.00%)	2/318 (0.63%)
Troponin I Increased ^* 1	1/318 (0.31%)	0/318 (0.00%)
Metabolism and nutrition disorders
Anorexia ^* 1	0/318 (0.00%)	2/318 (0.63%)
Dehydration ^* 1	6/318 (1.89%)	6/318 (1.89%)
Gout ^* 1	0/318 (0.00%)	1/318 (0.31%)
Hypercalcaemia ^* 1	1/318 (0.31%)	1/318 (0.31%)
Hyperkalaemia ^* 1	1/318 (0.31%)	0/318 (0.00%)
Hypoalbuminaemia ^* 1	1/318 (0.31%)	1/318 (0.31%)
Hypoglycaemia ^* 1	1/318 (0.31%)	0/318 (0.00%)
Hypokalaemia ^* 1	1/318 (0.31%)	3/318 (0.94%)
Hyponatraemia ^* 1	1/318 (0.31%)	1/318 (0.31%)
Musculoskeletal and connective tissue disorders
Arthralgia ^* 1	2/318 (0.63%)	0/318 (0.00%)
Back Pain ^* 1	3/318 (0.94%)	0/318 (0.00%)
Bone Lesion ^* 1	1/318 (0.31%)	1/318 (0.31%)
Bone Pain ^* 1	1/318 (0.31%)	1/318 (0.31%)
Bursitis ^* 1	0/318 (0.00%)	1/318 (0.31%)
Joint Instability ^* 1	0/318 (0.00%)	1/318 (0.31%)
Musculoskeletal Chest Pain ^* 1	0/318 (0.00%)	1/318 (0.31%)
Myalgia ^* 1	1/318 (0.31%)	0/318 (0.00%)
Osteonecrosis ^* 1	0/318 (0.00%)	1/318 (0.31%)
Pain in Extremity ^* 1	2/318 (0.63%)	0/318 (0.00%)
Pathological Fracture ^* 1	0/318 (0.00%)	2/318 (0.63%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer Pain ^* 1	1/318 (0.31%)	0/318 (0.00%)
Colon Cancer ^* 1	0/318 (0.00%)	1/318 (0.31%)
Tumour Lysis Syndrome ^* 1	1/318 (0.31%)	2/318 (0.63%)
Nervous system disorders
Autonomic Neuropathy ^* 1	1/318 (0.31%)	0/318 (0.00%)
Balance Disorder ^* 1	1/318 (0.31%)	0/318 (0.00%)
Cauda Equina Syndrome ^* 1	2/318 (0.63%)	1/318 (0.31%)
Cerebral Haemorrhage ^* 1	0/318 (0.00%)	1/318 (0.31%)
Cerebral Infarction ^* 1	0/318 (0.00%)	1/318 (0.31%)
Cerebral Ischaemia ^* 1	0/318 (0.00%)	1/318 (0.31%)
Coordination Abnormal ^* 1	0/318 (0.00%)	1/318 (0.31%)
Dizziness ^* 1	1/318 (0.31%)	2/318 (0.63%)
Lumbar Radiculopathy ^* 1	1/318 (0.31%)	0/318 (0.00%)
Neuralgia ^* 1	1/318 (0.31%)	0/318 (0.00%)
Neuropathy ^* 1	1/318 (0.31%)	0/318 (0.00%)
Neuropathy Peripheral ^* 1	1/318 (0.31%)	2/318 (0.63%)
Paralysis ^* 1	1/318 (0.31%)	0/318 (0.00%)
Paraparesis ^* 1	1/318 (0.31%)	0/318 (0.00%)
Paraplegia ^* 1	1/318 (0.31%)	0/318 (0.00%)
Polyneuropathy ^* 1	1/318 (0.31%)	1/318 (0.31%)
Polyneuropathy in Malignant Disease ^* 1	1/318 (0.31%)	0/318 (0.00%)
Quadriparesis ^* 1	1/318 (0.31%)	0/318 (0.00%)
Spinal Cord Compression ^* 1	0/318 (0.00%)	3/318 (0.94%)
Syncope ^* 1	4/318 (1.26%)	4/318 (1.26%)
Tremor ^* 1	0/318 (0.00%)	1/318 (0.31%)
Psychiatric disorders
Agitation ^* 1	1/318 (0.31%)	0/318 (0.00%)
Anxiety ^* 1	1/318 (0.31%)	0/318 (0.00%)
Completed Suicide ^* 1	1/318 (0.31%)	0/318 (0.00%)
Nervousness ^* 1	1/318 (0.31%)	0/318 (0.00%)
Suicidal Ideation ^* 1	1/318 (0.31%)	0/318 (0.00%)
Renal and urinary disorders
Calculus Bladder ^* 1	0/318 (0.00%)	1/318 (0.31%)
Haematuria ^* 1	0/318 (0.00%)	1/318 (0.31%)
Nephritis Interstitial ^* 1	1/318 (0.31%)	0/318 (0.00%)
Renal Colic ^* 1	0/318 (0.00%)	1/318 (0.31%)
Renal Failure ^* 1	2/318 (0.63%)	3/318 (0.94%)
Renal Failure Acute ^* 1	5/318 (1.57%)	4/318 (1.26%)
Renal Failure Chronic ^* 1	1/318 (0.31%)	0/318 (0.00%)
Renal Impairment ^* 1	2/318 (0.63%)	0/318 (0.00%)
Urinary Bladder Haemorrhage ^* 1	0/318 (0.00%)	1/318 (0.31%)
Urinary Retention ^* 1	2/318 (0.63%)	1/318 (0.31%)
Reproductive system and breast disorders
Benign Prostatic Hyperplasia ^* 1	0/318 (0.00%)	1/318 (0.31%)
Epididymitis ^* 1	1/318 (0.31%)	0/318 (0.00%)
Respiratory, thoracic and mediastinal disorders
Acute Pulmonary Oedema ^* 1	1/318 (0.31%)	2/318 (0.63%)
Chronic Obstructive Pulmonary Disease ^* 1	1/318 (0.31%)	0/318 (0.00%)
Dyspnoea ^* 1	6/318 (1.89%)	2/318 (0.63%)
Dyspnoea Exertional ^* 1	0/318 (0.00%)	1/318 (0.31%)
Interstitial Lung Disease ^* 1	1/318 (0.31%)	0/318 (0.00%)
Pneumonitis ^* 1	0/318 (0.00%)	2/318 (0.63%)
Pulmonary Embolism ^* 1	2/318 (0.63%)	2/318 (0.63%)
Pulmonary Fibrosis ^* 1	1/318 (0.31%)	0/318 (0.00%)
Pulmonary Hypertension ^* 1	0/318 (0.00%)	2/318 (0.63%)
Pulmonary Oedema ^* 1	0/318 (0.00%)	1/318 (0.31%)
Respiratory Failure ^* 1	1/318 (0.31%)	1/318 (0.31%)
Skin and subcutaneous tissue disorders
Epidermal Necrosis ^* 1	0/318 (0.00%)	1/318 (0.31%)
Jessner's Lymphocytic Infiltration ^* 1	1/318 (0.31%)	0/318 (0.00%)
Palmar-Plantar Erythrodysaesthesia Syndrome ^* 1	0/318 (0.00%)	1/318 (0.31%)
Rash ^* 1	0/318 (0.00%)	1/318 (0.31%)
Swelling Face ^* 1	1/318 (0.31%)	0/318 (0.00%)
Vascular disorders
Deep Vein Thrombosis ^* 1	1/318 (0.31%)	0/318 (0.00%)
Hypotension ^* 1	2/318 (0.63%)	4/318 (1.26%)
Orthostatic Hypotension ^* 1	2/318 (0.63%)	2/318 (0.63%)
Phlebitis ^* 1	0/318 (0.00%)	1/318 (0.31%)
Thrombophlebitis ^* 1	0/318 (0.00%)	1/318 (0.31%)
* Indicates events were collected by non-systematic assessment 1 Term from vocabulary, MedDRA Version 9.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Velcade (Bortezomib) Monotherapy	Doxil/Caelyx Plus Velcade (Bortezomib)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	299/318 (94.03%)	313/318 (98.43%)
Blood and lymphatic system disorders
Anaemia ^* 1	67/318 (21.07%)	80/318 (25.16%)
Leukopenia ^* 1	23/318 (7.23%)	28/318 (8.81%)
Neutropenia ^* 1	71/318 (22.33%)	113/318 (35.53%)
Thrombocytopenia ^* 1	89/318 (27.99%)	104/318 (32.70%)
Eye disorders
Conjunctivitis ^* 1	17/318 (5.35%)	24/318 (7.55%)
Gastrointestinal disorders
Abdominal Pain ^* 1	23/318 (7.23%)	32/318 (10.06%)
Abdominal Pain Upper ^* 1	13/318 (4.09%)	24/318 (7.55%)
Constipation ^* 1	98/318 (30.82%)	99/318 (31.13%)
Diarrhoea ^* 1	122/318 (38.36%)	142/318 (44.65%)
Dyspepsia ^* 1	13/318 (4.09%)	27/318 (8.49%)
Nausea ^* 1	125/318 (39.31%)	152/318 (47.80%)
Stomatitis ^* 1	11/318 (3.46%)	55/318 (17.30%)
Vomiting ^* 1	67/318 (21.07%)	93/318 (29.25%)
General disorders
Asthenia ^* 1	56/318 (17.61%)	70/318 (22.01%)
Chills ^* 1	18/318 (5.66%)	25/318 (7.86%)
Fatigue ^* 1	88/318 (27.67%)	115/318 (36.16%)
Influenza Like Illness ^* 1	13/318 (4.09%)	18/318 (5.66%)
Oedema Peripheral ^* 1	27/318 (8.49%)	32/318 (10.06%)
Pyrexia ^* 1	67/318 (21.07%)	91/318 (28.62%)
Infections and infestations
Bronchitis ^* 1	14/318 (4.40%)	25/318 (7.86%)
Herpes Simplex ^* 1	18/318 (5.66%)	32/318 (10.06%)
Herpes Zoster ^* 1	26/318 (8.18%)	30/318 (9.43%)
Nasopharyngitis ^* 1	20/318 (6.29%)	25/318 (7.86%)
Pneumonia ^* 1	9/318 (2.83%)	18/318 (5.66%)
Upper Respiratory Tract Infection ^* 1	32/318 (10.06%)	30/318 (9.43%)
Investigations
Aspartate Aminotransferase Increased ^* 1	11/318 (3.46%)	16/318 (5.03%)
Blood Creatinine Increased ^* 1	7/318 (2.20%)	16/318 (5.03%)
Weight Decreased ^* 1	12/318 (3.77%)	37/318 (11.64%)
Metabolism and nutrition disorders
Anorexia ^* 1	43/318 (13.52%)	58/318 (18.24%)
Decreased Appetite ^* 1	9/318 (2.83%)	30/318 (9.43%)
Hypocalcaemia ^* 1	9/318 (2.83%)	19/318 (5.97%)
Hypokalaemia ^* 1	15/318 (4.72%)	23/318 (7.23%)
Hypomagnesaemia ^* 1	12/318 (3.77%)	17/318 (5.35%)
Musculoskeletal and connective tissue disorders
Arthralgia ^* 1	27/318 (8.49%)	34/318 (10.69%)
Back Pain ^* 1	37/318 (11.64%)	38/318 (11.95%)
Bone Pain ^* 1	25/318 (7.86%)	10/318 (3.14%)
Musculoskeletal Chest Pain ^* 1	12/318 (3.77%)	20/318 (6.29%)
Myalgia ^* 1	20/318 (6.29%)	10/318 (3.14%)
Pain in Extremity ^* 1	47/318 (14.78%)	34/318 (10.69%)
Nervous system disorders
Dizziness ^* 1	27/318 (8.49%)	32/318 (10.06%)
Dysgeusia ^* 1	9/318 (2.83%)	18/318 (5.66%)
Headache ^* 1	56/318 (17.61%)	59/318 (18.55%)
Neuralgia ^* 1	63/318 (19.81%)	54/318 (16.98%)
Neuropathy ^* 1	38/318 (11.95%)	35/318 (11.01%)
Neuropathy Peripheral ^* 1	46/318 (14.47%)	36/318 (11.32%)
Paraesthesia ^* 1	31/318 (9.75%)	41/318 (12.89%)
Peripheral Sensory Neuropathy ^* 1	42/318 (13.21%)	41/318 (12.89%)
Polyneuropathy ^* 1	27/318 (8.49%)	26/318 (8.18%)
Psychiatric disorders
Depression ^* 1	16/318 (5.03%)	9/318 (2.83%)
Insomnia ^* 1	43/318 (13.52%)	35/318 (11.01%)
Respiratory, thoracic and mediastinal disorders
Cough ^* 1	38/318 (11.95%)	58/318 (18.24%)
Dyspnoea ^* 1	22/318 (6.92%)	32/318 (10.06%)
Epistaxis ^* 1	12/318 (3.77%)	18/318 (5.66%)
Skin and subcutaneous tissue disorders
Dry Skin ^* 1	7/318 (2.20%)	28/318 (8.81%)
Palmar-Plantar Erythrodysaesthesia Syndrome ^* 1	1/318 (0.31%)	62/318 (19.50%)
Pruritus ^* 1	16/318 (5.03%)	20/318 (6.29%)
Rash ^* 1	29/318 (9.12%)	48/318 (15.09%)
Vascular disorders
Hypertension ^* 1	17/318 (5.35%)	15/318 (4.72%)
* Indicates events were collected by non-systematic assessment 1 Term from vocabulary, MedDRA Version 9.0

Limitations and Caveats

Study stopped in terms of primary endpoint based on its results at planned interim analysis (28 Apr 2006). However, Long-term follow-up for survival continued until 16 May 2014.

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.

A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.

Results Point of Contact

Name/Title: Project Physician

Organization: Janssen R&D UK

EMail: ClinicalTrialDisclosure@its.jnj.com

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

Dimopoulos MA, Orlowski RZ, Facon T, Sonneveld P, Anderson KC, Beksac M, Benboubker L, Roddie H, Potamianou A, Couturier C, Feng H, Ataman O, van de Velde H, Richardson PG. Retrospective matched-pairs analysis of bortezomib plus dexamethasone versus bortezomib monotherapy in relapsed multiple myeloma. Haematologica. 2015 Jan;100(1):100-6. doi: 10.3324/haematol.2014.112037. Epub 2014 Sep 26.

Sonneveld P, Hajek R, Nagler A, Spencer A, Bladé J, Robak T, Zhuang SH, Harousseau JL, Orlowski RZ; DOXIL-MMY-3001 Study Investigators. Combined pegylated liposomal doxorubicin and bortezomib is highly effective in patients with recurrent or refractory multiple myeloma who received prior thalidomide/lenalidomide therapy. Cancer. 2008 Apr 1;112(7):1529-37. doi: 10.1002/cncr.23326.

Orlowski RZ, Nagler A, Sonneveld P, Bladé J, Hajek R, Spencer A, San Miguel J, Robak T, Dmoszynska A, Horvath N, Spicka I, Sutherland HJ, Suvorov AN, Zhuang SH, Parekh T, Xiu L, Yuan Z, Rackoff W, Harousseau JL. Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: combination therapy improves time to progression. J Clin Oncol. 2007 Sep 1;25(25):3892-901. Epub 2007 Aug 6.

Responsible Party:	Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:	NCT00103506 History of Changes
Other Study ID Numbers:	CR004117 DOXILMMY3001 ( Other Identifier: Janssen Research & Development, LLC ) 2004-001842-34 ( EudraCT Number )
First Submitted:	February 9, 2005
First Posted:	February 10, 2005
Results First Submitted:	May 8, 2015
Results First Posted:	May 25, 2015
Last Update Posted:	October 19, 2015

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