Trial Outcomes & Findings for Study of DOXIL/CAELYX (Pegylated Liposomal Doxorubicin) and VELCADE (Bortezomib) or VELCADE Monotherapy for the Treatment of Relapsed Multiple Myeloma (NCT NCT00103506)

Last Updated: 2015-10-19

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

646 participants

Primary outcome timeframe

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])

Results posted on

2015-10-19

Participant Flow

Participant milestones

Participant milestones
Measure	Velcade (Bortezomib) Monotherapy 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.	Doxil/Caelyx Plus Velcade (Bortezomib) 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 Study STARTED	322	324
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	322	324

Reasons for withdrawal

Reasons for withdrawal
Measure	Velcade (Bortezomib) Monotherapy 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.	Doxil/Caelyx Plus Velcade (Bortezomib) 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 Study Study closed by sponsor	34	37
Overall Study Death	257	253
Overall Study Lost to Follow-up	13	13
Overall Study Withdrawal by Subject	18	21

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Velcade (Bortezomib) Monotherapy n=322 Participants 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.	Doxil/Caelyx Plus Velcade (Bortezomib) n=324 Participants 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 n=646 Participants Total of all reporting groups
Age, Continuous	61.5 years STANDARD_DEVIATION 9.56 • n=5 Participants	61.4 years STANDARD_DEVIATION 9.61 • n=7 Participants	61.4 years STANDARD_DEVIATION 9.58 • n=5 Participants
Sex: Female, Male Female	148 Participants n=5 Participants	135 Participants n=7 Participants	283 Participants n=5 Participants
Sex: Female, Male Male	174 Participants n=5 Participants	189 Participants n=7 Participants	363 Participants n=5 Participants
Region of Enrollment ARGENTINA	6 participants n=5 Participants	9 participants n=7 Participants	15 participants n=5 Participants
Region of Enrollment AUSTRALIA	31 participants n=5 Participants	31 participants n=7 Participants	62 participants n=5 Participants
Region of Enrollment AUSTRIA	12 participants n=5 Participants	6 participants n=7 Participants	18 participants n=5 Participants
Region of Enrollment BELGIUM-LUXEMBURG	6 participants n=5 Participants	14 participants n=7 Participants	20 participants n=5 Participants
Region of Enrollment CANADA	20 participants n=5 Participants	23 participants n=7 Participants	43 participants n=5 Participants
Region of Enrollment CZECH REPUBLIC	14 participants n=5 Participants	22 participants n=7 Participants	36 participants n=5 Participants
Region of Enrollment FRANCE	21 participants n=5 Participants	28 participants n=7 Participants	49 participants n=5 Participants
Region of Enrollment GREAT BRITAIN	8 participants n=5 Participants	7 participants n=7 Participants	15 participants n=5 Participants
Region of Enrollment ISRAEL	25 participants n=5 Participants	21 participants n=7 Participants	46 participants n=5 Participants
Region of Enrollment ITALY	17 participants n=5 Participants	11 participants n=7 Participants	28 participants n=5 Participants
Region of Enrollment NETHERLANDS	29 participants n=5 Participants	32 participants n=7 Participants	61 participants n=5 Participants
Region of Enrollment POLAND	35 participants n=5 Participants	17 participants n=7 Participants	52 participants n=5 Participants
Region of Enrollment PORTUGAL	6 participants n=5 Participants	14 participants n=7 Participants	20 participants n=5 Participants
Region of Enrollment RUSSIA	38 participants n=5 Participants	34 participants n=7 Participants	72 participants n=5 Participants
Region of Enrollment SINGAPORE	3 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment SOUTH AFRICA	13 participants n=5 Participants	15 participants n=7 Participants	28 participants n=5 Participants
Region of Enrollment SPAIN	20 participants n=5 Participants	15 participants n=7 Participants	35 participants n=5 Participants
Region of Enrollment UNITED STATES OF AMERICA	18 participants n=5 Participants	23 participants n=7 Participants	41 participants n=5 Participants

PRIMARY outcome

Timeframe: 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])

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

Outcome measures

Outcome measures
Measure	Velcade (Bortezomib) Monotherapy n=322 Participants 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.	Doxil/Caelyx Plus Velcade (Bortezomib) n=324 Participants 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.
Time to Progression (TTP)	6.5 Months Interval 5.6 to 7.1	9.3 Months Interval 8.2 to 11.1

SECONDARY outcome

Timeframe: 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)

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.

Outcome measures

Outcome measures
Measure	Velcade (Bortezomib) Monotherapy n=322 Participants 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.	Doxil/Caelyx Plus Velcade (Bortezomib) n=324 Participants 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 Survival	30.8 months Interval 25.2 to 36.5	33.0 months Interval 28.9 to 37.1

SECONDARY outcome

Timeframe: 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)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Velcade (Bortezomib) Monotherapy n=318 Participants 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.	Doxil/Caelyx Plus Velcade (Bortezomib) n=318 Participants 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.
Number of Participants With Serious Adverse Events (SAEs)	105 Participants	120 Participants

Adverse Events

Velcade (Bortezomib) Monotherapy

Serious events: 105 serious events

Other events: 299 other events

Deaths: 0 deaths

Doxil/Caelyx Plus Velcade (Bortezomib)

Serious events: 120 serious events

Other events: 313 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Project Physician

Janssen R&D UK

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Velcade (Bortezomib) Monotherapy n=318 participants at risk 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.	Doxil/Caelyx Plus Velcade (Bortezomib) n=318 participants at risk 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.
Blood and lymphatic system disorders Anaemia	21.1% 67/318 Safety population included all the participants who received at least one dose of study drug.	25.2% 80/318 Safety population included all the participants who received at least one dose of study drug.
Blood and lymphatic system disorders Leukopenia	7.2% 23/318 Safety population included all the participants who received at least one dose of study drug.	8.8% 28/318 Safety population included all the participants who received at least one dose of study drug.
Blood and lymphatic system disorders Neutropenia	22.3% 71/318 Safety population included all the participants who received at least one dose of study drug.	35.5% 113/318 Safety population included all the participants who received at least one dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	28.0% 89/318 Safety population included all the participants who received at least one dose of study drug.	32.7% 104/318 Safety population included all the participants who received at least one dose of study drug.
Eye disorders Conjunctivitis	5.3% 17/318 Safety population included all the participants who received at least one dose of study drug.	7.5% 24/318 Safety population included all the participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal Pain	7.2% 23/318 Safety population included all the participants who received at least one dose of study drug.	10.1% 32/318 Safety population included all the participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal Pain Upper	4.1% 13/318 Safety population included all the participants who received at least one dose of study drug.	7.5% 24/318 Safety population included all the participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	30.8% 98/318 Safety population included all the participants who received at least one dose of study drug.	31.1% 99/318 Safety population included all the participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	38.4% 122/318 Safety population included all the participants who received at least one dose of study drug.	44.7% 142/318 Safety population included all the participants who received at least one dose of study drug.
Gastrointestinal disorders Dyspepsia	4.1% 13/318 Safety population included all the participants who received at least one dose of study drug.	8.5% 27/318 Safety population included all the participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	39.3% 125/318 Safety population included all the participants who received at least one dose of study drug.	47.8% 152/318 Safety population included all the participants who received at least one dose of study drug.
Gastrointestinal disorders Stomatitis	3.5% 11/318 Safety population included all the participants who received at least one dose of study drug.	17.3% 55/318 Safety population included all the participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	21.1% 67/318 Safety population included all the participants who received at least one dose of study drug.	29.2% 93/318 Safety population included all the participants who received at least one dose of study drug.
General disorders Asthenia	17.6% 56/318 Safety population included all the participants who received at least one dose of study drug.	22.0% 70/318 Safety population included all the participants who received at least one dose of study drug.
General disorders Chills	5.7% 18/318 Safety population included all the participants who received at least one dose of study drug.	7.9% 25/318 Safety population included all the participants who received at least one dose of study drug.
General disorders Fatigue	27.7% 88/318 Safety population included all the participants who received at least one dose of study drug.	36.2% 115/318 Safety population included all the participants who received at least one dose of study drug.
General disorders Influenza Like Illness	4.1% 13/318 Safety population included all the participants who received at least one dose of study drug.	5.7% 18/318 Safety population included all the participants who received at least one dose of study drug.
General disorders Oedema Peripheral	8.5% 27/318 Safety population included all the participants who received at least one dose of study drug.	10.1% 32/318 Safety population included all the participants who received at least one dose of study drug.
General disorders Pyrexia	21.1% 67/318 Safety population included all the participants who received at least one dose of study drug.	28.6% 91/318 Safety population included all the participants who received at least one dose of study drug.
Infections and infestations Bronchitis	4.4% 14/318 Safety population included all the participants who received at least one dose of study drug.	7.9% 25/318 Safety population included all the participants who received at least one dose of study drug.
Infections and infestations Herpes Simplex	5.7% 18/318 Safety population included all the participants who received at least one dose of study drug.	10.1% 32/318 Safety population included all the participants who received at least one dose of study drug.
Infections and infestations Herpes Zoster	8.2% 26/318 Safety population included all the participants who received at least one dose of study drug.	9.4% 30/318 Safety population included all the participants who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	6.3% 20/318 Safety population included all the participants who received at least one dose of study drug.	7.9% 25/318 Safety population included all the participants who received at least one dose of study drug.
Infections and infestations Pneumonia	2.8% 9/318 Safety population included all the participants who received at least one dose of study drug.	5.7% 18/318 Safety population included all the participants who received at least one dose of study drug.
Infections and infestations Upper Respiratory Tract Infection	10.1% 32/318 Safety population included all the participants who received at least one dose of study drug.	9.4% 30/318 Safety population included all the participants who received at least one dose of study drug.
Investigations Aspartate Aminotransferase Increased	3.5% 11/318 Safety population included all the participants who received at least one dose of study drug.	5.0% 16/318 Safety population included all the participants who received at least one dose of study drug.
Investigations Blood Creatinine Increased	2.2% 7/318 Safety population included all the participants who received at least one dose of study drug.	5.0% 16/318 Safety population included all the participants who received at least one dose of study drug.
Investigations Weight Decreased	3.8% 12/318 Safety population included all the participants who received at least one dose of study drug.	11.6% 37/318 Safety population included all the participants who received at least one dose of study drug.
Metabolism and nutrition disorders Anorexia	13.5% 43/318 Safety population included all the participants who received at least one dose of study drug.	18.2% 58/318 Safety population included all the participants who received at least one dose of study drug.
Metabolism and nutrition disorders Decreased Appetite	2.8% 9/318 Safety population included all the participants who received at least one dose of study drug.	9.4% 30/318 Safety population included all the participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypocalcaemia	2.8% 9/318 Safety population included all the participants who received at least one dose of study drug.	6.0% 19/318 Safety population included all the participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	4.7% 15/318 Safety population included all the participants who received at least one dose of study drug.	7.2% 23/318 Safety population included all the participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypomagnesaemia	3.8% 12/318 Safety population included all the participants who received at least one dose of study drug.	5.3% 17/318 Safety population included all the participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	8.5% 27/318 Safety population included all the participants who received at least one dose of study drug.	10.7% 34/318 Safety population included all the participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back Pain	11.6% 37/318 Safety population included all the participants who received at least one dose of study drug.	11.9% 38/318 Safety population included all the participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Bone Pain	7.9% 25/318 Safety population included all the participants who received at least one dose of study drug.	3.1% 10/318 Safety population included all the participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal Chest Pain	3.8% 12/318 Safety population included all the participants who received at least one dose of study drug.	6.3% 20/318 Safety population included all the participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	6.3% 20/318 Safety population included all the participants who received at least one dose of study drug.	3.1% 10/318 Safety population included all the participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Pain in Extremity	14.8% 47/318 Safety population included all the participants who received at least one dose of study drug.	10.7% 34/318 Safety population included all the participants who received at least one dose of study drug.
Nervous system disorders Dizziness	8.5% 27/318 Safety population included all the participants who received at least one dose of study drug.	10.1% 32/318 Safety population included all the participants who received at least one dose of study drug.
Nervous system disorders Dysgeusia	2.8% 9/318 Safety population included all the participants who received at least one dose of study drug.	5.7% 18/318 Safety population included all the participants who received at least one dose of study drug.
Nervous system disorders Headache	17.6% 56/318 Safety population included all the participants who received at least one dose of study drug.	18.6% 59/318 Safety population included all the participants who received at least one dose of study drug.
Nervous system disorders Neuralgia	19.8% 63/318 Safety population included all the participants who received at least one dose of study drug.	17.0% 54/318 Safety population included all the participants who received at least one dose of study drug.
Nervous system disorders Neuropathy	11.9% 38/318 Safety population included all the participants who received at least one dose of study drug.	11.0% 35/318 Safety population included all the participants who received at least one dose of study drug.
Nervous system disorders Neuropathy Peripheral	14.5% 46/318 Safety population included all the participants who received at least one dose of study drug.	11.3% 36/318 Safety population included all the participants who received at least one dose of study drug.
Nervous system disorders Paraesthesia	9.7% 31/318 Safety population included all the participants who received at least one dose of study drug.	12.9% 41/318 Safety population included all the participants who received at least one dose of study drug.
Nervous system disorders Peripheral Sensory Neuropathy	13.2% 42/318 Safety population included all the participants who received at least one dose of study drug.	12.9% 41/318 Safety population included all the participants who received at least one dose of study drug.
Nervous system disorders Polyneuropathy	8.5% 27/318 Safety population included all the participants who received at least one dose of study drug.	8.2% 26/318 Safety population included all the participants who received at least one dose of study drug.
Psychiatric disorders Depression	5.0% 16/318 Safety population included all the participants who received at least one dose of study drug.	2.8% 9/318 Safety population included all the participants who received at least one dose of study drug.
Psychiatric disorders Insomnia	13.5% 43/318 Safety population included all the participants who received at least one dose of study drug.	11.0% 35/318 Safety population included all the participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	11.9% 38/318 Safety population included all the participants who received at least one dose of study drug.	18.2% 58/318 Safety population included all the participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.9% 22/318 Safety population included all the participants who received at least one dose of study drug.	10.1% 32/318 Safety population included all the participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	3.8% 12/318 Safety population included all the participants who received at least one dose of study drug.	5.7% 18/318 Safety population included all the participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Dry Skin	2.2% 7/318 Safety population included all the participants who received at least one dose of study drug.	8.8% 28/318 Safety population included all the participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Palmar-Plantar Erythrodysaesthesia Syndrome	0.31% 1/318 Safety population included all the participants who received at least one dose of study drug.	19.5% 62/318 Safety population included all the participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	5.0% 16/318 Safety population included all the participants who received at least one dose of study drug.	6.3% 20/318 Safety population included all the participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash	9.1% 29/318 Safety population included all the participants who received at least one dose of study drug.	15.1% 48/318 Safety population included all the participants who received at least one dose of study drug.
Vascular disorders Hypertension	5.3% 17/318 Safety population included all the participants who received at least one dose of study drug.	4.7% 15/318 Safety population included all the participants who received at least one dose of study drug.