VCAT: Velcade (Bortezomib) Consolidation After Transplant

• Sponsor: Janssen Scientific Affairs, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01539083
• Collaborator: (none)
• Enrollment: 256
• Locations: 23
• Arms: 3
• Actual Duration (Months): 71.9
• Patients Per Site: 11.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if bortezomib when added to consolidation treatment with thalidomide and prednisolone leads to an improved response in patients with multiple myeloma who have undergone autologous stem cell transplant and initial treatment with bortezomib, cyclophosphamide, and dexamethasone.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Thalidomide; Drug: Bortezomib; Drug: Cyclophosphamide; Drug: Dexamethasone; Drug: Prednisolone	Phase 3

Detailed Description

This is an open-label (patients will know the identity of study treatments), randomized (patients will be assigned by chance to different treatments) study of bortezomib administered as consolidation therapy (therapy given once a remission is achieved) with thalidomide and prednisolone versus thalidomide and prednisolone alone in previously untreated patients with multiple myeloma. Multiple myeloma is a cancer of your plasma cells, a type of white blood cell present in your bone marrow. Patients in this study will receive initial therapy with bortezomib, cyclophosphamide, and dexamethasone (referred to as VCD induction therapy) and will undergo autologous stem cell transplant (ASCT) (a procedure where patients receive an infusion of immature blood cells [stem cells] from their own body to replenish the body's supply of healthy blood-forming cells) before randomization to one of two treatments: Treatment A (thalidomide for up to 12 months or until disease progression and prednisolone on alternate days continued indefinitely or until disease progression) or Treatment B (bortezomib for 32 weeks in addition to thalidomide up to 12 months or until disease progression and prednisolone on alternate days, continued indefinitely or until disease progression.

Throughout the study, the patient's response to therapy will be assessed according to protocol-defined efficacy evaluations and by implementing defined disease response criteria (International Myeloma Working Group [IMWG] criteria). Safety will be evaluated throughout the study. Follow up for progression-free survival (PFS) and overall survival (OS) will be conducted from time of randomization to 3 years post-randomization.

Two interim analyses are planned. The final analysis will be conducted after all patients have completed 12-month consolidation treatment phase or discontinued. The primary endpoint of number and percent of patients with complete response and very good partial response defined by IMWG criteria for multiple myeloma will be examined in the interim and final analyses after approximately 12 months of consolidation therapy. At the completion of the study, updated analyses of PFS and OS will be performed.

Study Design

• Study Type: Interventional
• Actual Enrollment: 256 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Randomised Trial of Bortezomib Consolidation (With Thalidomide and Prednisolone) Vs Thalidomide and Prednisolone Alone in Previously Untreated Subjects With Multiple Myeloma After Receiving Bortezomib, Cyclophosphamide, Dexamethasone (VCD) Induction and Autologous Stem Cell Transplant
• Actual Study Start Date: Jan 13, 2012
• Actual Primary Completion Date: Dec 30, 2015
• Actual Study Completion Date: Jan 9, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bortezomib + Cyclophosphamide + Dexamethasone [VCD Induction] Bortezomib (Velcade) 1.3 milligram per square meter (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11; cyclophosphamide 300 mg/m^2 orally on Days 1, 8, and 15; and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11, and 12 in three 21-day treatment cycles. Participants who completed induction phase entered into the consolidation treatment phase.	Drug: Bortezomib; Bortezomib 1.3 milligram per square meter (mg/m^2) solution for injection subcutaneously (SC).; Drug: Cyclophosphamide; Cyclophosphamide 300 mg/m^2 orally.; Drug: Dexamethasone; Dexamethasone 20 mg orally.
Experimental: Thalidomide + Prednisolone [TP Consolidation] Thalidomide 100 mg orally, once daily until disease progression (up to maximum of 12 months) and prednisolone 50 mg orally, on every alternate day until disease progression.	Drug: Thalidomide; Thalidomide 100 mg tablet, orally.; Drug: Prednisolone; Prednisolone 50 mg orally.
Experimental: Bortezomib + Thalidomide + Prednisolone [VTP Consolidation] Bortezomib 1.3 mg/m^2 SC every 2 weeks for 32 weeks in addition to thalidomide 100 mg orally, once daily for a maximum of 12 months or until disease progression and prednisolone 50 mg orally, on every alternate day until disease progression.	Drug: Thalidomide; Thalidomide 100 mg tablet, orally.; Drug: Bortezomib; Bortezomib 1.3 milligram per square meter (mg/m^2) solution for injection subcutaneously (SC).; Drug: Prednisolone; Prednisolone 50 mg orally.

Outcome Measures

Primary Outcome Measures

1. Consolidation Phase: Percentage of Participants With Complete Response (CR) and Very Good Partial Response (VGPR) at Month 12 [Month 12]

   CR as per IMWG criteria is defined as negative immunofixation on the serum and urine and disappearance of soft tissue plasmacytomas and less than (<) 5 percent plasma cells in bone marrow. VGPR as per IMWG criteria is defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90 percent or greater reduction in serum M-protein plus urine M-protein level <100 milligram (mg) per 24 hours.

Secondary Outcome Measures

1. Consolidation Phase: Percentage of Participants With Complete Response (CR) at Months 3, 6, 9 and 12 [Months 3, 6, 9 and 12]

   CR as per IMWG criteria is negative immunofixation on serum and urine and disappearance of soft tissue plasmacytomas and <5 percent plasma cells in bone marrow.

2. Consolidation Phase: Percentage of Participants With Stringent Complete Response (sCR) at Months 3, 6, 9 and 12 [Months 3, 6, 9 and 12]

   sCR as per IMWG criteria is CR plus normal free light chain (FLC) ratio and absence of clonal cells in bone marrow. CR is negative immunofixation on serum and urine and disappearance of soft tissue plasmacytomas and <5 percent plasma cells in bone marrow.

3. Progression Free Survival (PFS) [Baseline until progressive disease (up to 5 years)]

   PFS, calculated as the time between randomization to disease progression or death (regardless of cause), whichever occurred first. Progressive disease as per IMWG criteria: increase of >= 25 percent from lowest response level in Serum M-component and/or (the absolute increase must be >=0.5 gram per deciliter [g/dL]) Urine M-component and/or (the absolute increase must be >=200 mg/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 must be >10 mg/dL. Bone marrow plasma cell percentage: the absolute percent must be >=10 percent. Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas. Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.65 millimole per liter (mmol/L) that can be attributed solely to the plasma cell proliferative disorder.

4. Disease-free Survival (DFS) [Up to 5 years]

   DFS, defined as the duration from the start of CR to the time of relapse from CR. DFS applied only to participants in CR. CR as per IMWG criteria is negative immunofixation on serum and urine and disappearance of soft tissue plasmacytomas and <5 percent plasma cells in bone marrow. Relapse from CR: reappearance of serum or urine M-protein by immunofixation or electrophoresis; development of >= 5 percent plasma cells in the bone marrow; appearance of any other sign of progression (ie, new plasmacytoma, lytic bone lesion, or hypercalcaemia).

5. Overall Survival (OS) [Up to 5 years]

   OS was defined as the time between randomization and death. Death of a participant regardless of the cause was considered as an event.

6. Consolidation Phase: Change From Baseline in AQOL-6D Scores at the End of the Consolidation Phase [Baseline, Month 12]

   The assessment of quality of life-6D (AQoL-6D) is a multi-attribute health-related quality of life instrument (QoL). It comprises dimension scores for independent living, relationships, mental health, coping, pain, senses, and utility score for AQol-6D. Each scale ranges between 1 (best QoL) and -0.04 (worst possible QoL).

7. Consolidation Phase: Change From Baseline in FACT/GOG-NTX Total Score at the End of the Consolidation Phase [Baseline, Month 12]

   Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX) consists of 10 items and evaluates symptoms and concerns associated specifically with chemotherapy-induced neuropathy. 1 FACT/GOG-NTX total score has a range of 0 to 108 with a higher score indicating better quality of life.

Eligibility Criteria

Criteria

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

Inclusion criteria:

• Previously diagnosed with multiple myeloma based on international myeloma working group (IMWG) criteria.and meet all of the following; Serum M-protein greater than or equal to (>=) 1 gram per deciliter (g/dL) (>=10 gram per liter); Urine M-protein >=200 milligram (mg) per 24 hour and Serum Free Light chain (FLC) assay: Involved FLC Level

=10 mg/dL (>=100 mg/L) provided serum FLC ratio is normal

• Meet the pretreatment laboratory criteria as specified in the study protocol at and within 21 days before baseline (Day 1 of Cycle 1, before bortezomib administration for induction).

• Have ECOG status 0-2.

• Men and women must practice an appropriate method of birth control as specified in the study protocol from signing of the informed consent form though to the 12-month visit/early termination visit.

Exclusion criteria:

• Has previously received treatment for multiple myeloma (including prior therapy with radiation or pulsed dexamethasone) as specified in the study protocol.

• Has a history of any other malignancy within 5 years before enrolment as specified in the study protocol.

• Has had major surgery as specified in the study protocol within 30 days before enrolment.

• Had a myocardial infarction within 6 months of enrolment or has New York Heart Association (NYHA) Class III or IV heart failure (or other clinically significant cardiac medical history as specified in the study protocol).

• Has any condition that, in the opinion of the investigator, would make participation not be in the best interest (eg, compromise the well-being) of the patient or that could prevent, limit, or confound the protocol-specified assessments.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Adelaide		Australia
2		Camperdown		Australia
3		Geelong		Australia
4		Greenslopes		Australia
5		Heidelberg		Australia
6		Herston		Australia
7		Malvern		Australia
8		Melbourne		Australia
9		Nedlands		Australia
10		Newcastle		Australia
11		Prahran		Australia
12		Sydney		Australia
13		Westmead		Australia
14		Woodville South		Australia
15		Woolloongabba		Australia
16		Beijing		China
17		Guangzhou		China
18		Shanghai		China
19		Tianjin		China
20		Busan		Korea, Republic of
21		Daegu		Korea, Republic of
22		Hwasun Gun		Korea, Republic of
23		Ulsan		Korea, Republic of

Sponsors and Collaborators

• Janssen Scientific Affairs, LLC

Investigators

• Study Director: Janssen Asia-Pacific Medical Affairs Clinical Trial, Janssen Asia-Pacific Medical Affairs

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen Scientific Affairs, LLC
• ClinicalTrials.gov Identifier: NCT01539083
• Other Study ID Numbers: CR018751; 26866138-MMY-2073
• First Posted: Feb 27, 2012
• Last Update Posted: Dec 27, 2018
• Last Verified: Nov 1, 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Janssen Scientific Affairs, LLC: Multiple Myeloma; Bortezomib; VELCADE; Consolidation therapy; Subcutaneous; Thalidomide; Prednisolone; Autologous stem cell transplant (ASCT); VELCADE, cyclophosphamide, dexamethasone (VCD) induction therapy
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Thalidomide; Dexamethasone; Prednisolone; Cyclophosphamide; Bortezomib

Study Results

Participant Flow

Pre-assignment Detail	The study consisted of 2 treatment phases: induction and consolidation. Participants who completed the induction phase were randomized to enter in the consolidation treatment phase.

Arm/Group Title	Bortezomib + Cyclophosphamide + Dexamethasone (VCD Induction)	Thalidomide + Prednisolone (TP Consolidation)	Bortezomib + Thalidomide + Prednisolone (VTP Consolidation)
Arm/Group Description	Participants received bortezomib (Velcade) 1.3 milligram per square meter (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11; cyclophosphamide 300 mg/m^2 orally on Days 1, 8, and 15; and dexamethasone 20 milligram (mg) orally on Days 1, 2, 4, 5, 8, 9, 11, and 12 in three 21-day treatment cycles. Participants who completed induction phase entered into the consolidation treatment phase.	Participants who completed induction phase entered in the consolidated treatment phase and received thalidomide 100 mg orally, once daily until disease progression (up to maximum of 12 months) and prednisolone 50 mg orally, on every alternate day until disease progression.	Participants who completed induction phase entered in the consolidated treatment phase and received bortezomib 1.3 mg/m^2 SC every 2 weeks for 32 weeks in addition to thalidomide 100 mg orally, once daily for a maximum of 12 months or until disease progression and prednisolone 50 mg orally, on every alternate day until disease progression.
Period Title: Before Randomization (VCD Induction)
STARTED	256	0	0
Treated	254	0	0
COMPLETED	203	0	0
NOT COMPLETED	53	0	0
Period Title: Before Randomization (VCD Induction)
STARTED	0	100	103
Safety Population	0	99	103
COMPLETED	0	79	80
NOT COMPLETED	0	21	23

Baseline Characteristics

Arm/Group Title	Bortezomib + Cyclophosphamide + Dexamethasone (VCD Induction)
Arm/Group Description	Participants received bortezomib (Velcade) 1.3 milligram per square meter (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11; cyclophosphamide 300 mg/m^2 orally on Days 1, 8, and 15; and dexamethasone 20 milligram (mg) orally on Days 1, 2, 4, 5, 8, 9, 11, and 12 in three 21-day treatment cycles. Participants who completed induction phase entered into the consolidation treatment phase.
Overall Participants	254
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.8 (7.76)
Sex: Female, Male (Count of Participants)
Female	109 42.9%
Male	145 57.1%
Region of Enrollment (Count of Participants)
Australia	207 81.5%
China	17 6.7%
Republic of Korea	30 11.8%

Outcome Measures

1. Primary Outcome

Title	Consolidation Phase: Percentage of Participants With Complete Response (CR) and Very Good Partial Response (VGPR) at Month 12
Description	CR as per IMWG criteria is defined as negative immunofixation on the serum and urine and disappearance of soft tissue plasmacytomas and less than (<) 5 percent plasma cells in bone marrow. VGPR as per IMWG criteria is defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90 percent or greater reduction in serum M-protein plus urine M-protein level <100 milligram (mg) per 24 hours.
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

All response-evaluable-randomized analysis set was defined as all participants in the response-evaluable-induction set (all participants who received at least 1 dose of study medication in the induction phase and had measurable disease at baseline) who were randomized to receive consolidation treatment.

Arm/Group Title	Thalidomide + Prednisolone [TP Consolidation]	Bortezomib + Thalidomide + Prednisolone [VTP Consolidation]
Arm/Group Description	Participants who completed induction phase entered in the consolidated treatment phase and received thalidomide 100 mg orally, once daily until disease progression (up to maximum of 12 months) and prednisolone 50 mg orally, on every alternate day until disease progression.	Participants who completed induction phase entered in the consolidated treatment phase and received bortezomib 1.3 mg/m^2 SC every 2 weeks for 32 weeks in addition to thalidomide 100 mg orally, once daily for a maximum of 12 months or until disease progression and prednisolone 50 mg orally, on every alternate day until disease progression.
Measure Participants	96	98
Number [percentage of participants]	81.3 32%	92.9 NaN

2. Secondary Outcome

Title	Consolidation Phase: Percentage of Participants With Complete Response (CR) at Months 3, 6, 9 and 12
Description	CR as per IMWG criteria is negative immunofixation on serum and urine and disappearance of soft tissue plasmacytomas and <5 percent plasma cells in bone marrow.
Time Frame	Months 3, 6, 9 and 12

Outcome Measure Data

Analysis Population Description

All response-evaluable-randomized analysis set was defined as all participants in the response-evaluable-induction set (all participants who received at least 1 dose of study medication in the induction phase and had measurable disease at baseline) who were randomized to receive consolidation treatment.

Arm/Group Title	Thalidomide + Prednisolone [TP Consolidation]	Bortezomib + Thalidomide + Prednisolone [VTP Consolidation]
Arm/Group Description	Participants who completed induction phase entered in the consolidated treatment phase and received thalidomide 100 mg orally, once daily until disease progression (up to maximum of 12 months) and prednisolone 50 mg orally, on every alternate day until disease progression.	Participants who completed induction phase entered in the consolidated treatment phase and received bortezomib 1.3 mg/m^2 SC every 2 weeks for 32 weeks in addition to thalidomide 100 mg orally, once daily for a maximum of 12 months or until disease progression and prednisolone 50 mg orally, on every alternate day until disease progression.
Measure Participants	96	98
Month 3	36.5 14.4%	36.7 NaN
Month 6	44.8 17.6%	44.9 NaN
Month 9	49.0 19.3%	52.0 NaN
Month 12	51.0 20.1%	53.1 NaN

3. Secondary Outcome

Title	Consolidation Phase: Percentage of Participants With Stringent Complete Response (sCR) at Months 3, 6, 9 and 12
Description	sCR as per IMWG criteria is CR plus normal free light chain (FLC) ratio and absence of clonal cells in bone marrow. CR is negative immunofixation on serum and urine and disappearance of soft tissue plasmacytomas and <5 percent plasma cells in bone marrow.
Time Frame	Months 3, 6, 9 and 12

Outcome Measure Data

Analysis Population Description

All response-evaluable-randomized analysis set was defined as all participants in the response-evaluable-induction set (all participants who received at least 1 dose of study medication in the induction phase and had measurable disease at baseline) who were randomized to receive consolidation treatment.

Arm/Group Title	Thalidomide + Prednisolone [TP Consolidation]	Bortezomib + Thalidomide + Prednisolone [VTP Consolidation]
Arm/Group Description	Participants who completed induction phase entered in the consolidated treatment phase and received thalidomide 100 mg orally, once daily until disease progression (up to maximum of 12 months) and prednisolone 50 mg orally, on every alternate day until disease progression.	Participants who completed induction phase entered in the consolidated treatment phase and received bortezomib 1.3 mg/m^2 SC every 2 weeks for 32 weeks in addition to thalidomide 100 mg orally, once daily for a maximum of 12 months or until disease progression and prednisolone 50 mg orally, on every alternate day until disease progression.
Measure Participants	96	98
Month 3	20.8 8.2%	23.5 NaN
Month 6	27.1 10.7%	28.6 NaN
Month 9	26.0 10.2%	30.6 NaN
Month 12	26.0 10.2%	28.6 NaN

4. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	PFS, calculated as the time between randomization to disease progression or death (regardless of cause), whichever occurred first. Progressive disease as per IMWG criteria: increase of >= 25 percent from lowest response level in Serum M-component and/or (the absolute increase must be >=0.5 gram per deciliter [g/dL]) Urine M-component and/or (the absolute increase must be >=200 mg/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 must be >10 mg/dL. Bone marrow plasma cell percentage: the absolute percent must be >=10 percent. Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas. Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.65 millimole per liter (mmol/L) that can be attributed solely to the plasma cell proliferative disorder.
Time Frame	Baseline until progressive disease (up to 5 years)

Outcome Measure Data

Analysis Population Description

All response-evaluable-randomized analysis set was defined as all participants in the response-evaluable-induction set (all participants who received at least 1 dose of study medication in the induction phase and had measurable disease at baseline) who were randomized to receive consolidation treatment.

Arm/Group Title	Thalidomide + Prednisolone [TP Consolidation]	Bortezomib + Thalidomide + Prednisolone [VTP Consolidation]
Arm/Group Description	Participants who completed induction phase entered in the consolidated treatment phase and received thalidomide 100 mg orally, once daily until disease progression (up to maximum of 12 months) and prednisolone 50 mg orally, on every alternate day until disease progression.	Participants who completed induction phase entered in the consolidated treatment phase and received bortezomib 1.3 mg/m^2 SC every 2 weeks for 32 weeks in addition to thalidomide 100 mg orally, once daily for a maximum of 12 months or until disease progression and prednisolone 50 mg orally, on every alternate day until disease progression.
Measure Participants	96	98
Median (95% Confidence Interval) [months]	22.05	22.51

5. Secondary Outcome

Title	Disease-free Survival (DFS)
Description	DFS, defined as the duration from the start of CR to the time of relapse from CR. DFS applied only to participants in CR. CR as per IMWG criteria is negative immunofixation on serum and urine and disappearance of soft tissue plasmacytomas and <5 percent plasma cells in bone marrow. Relapse from CR: reappearance of serum or urine M-protein by immunofixation or electrophoresis; development of >= 5 percent plasma cells in the bone marrow; appearance of any other sign of progression (ie, new plasmacytoma, lytic bone lesion, or hypercalcaemia).
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Response-evaluable-randomized analysis set defined as all participants in the response-evaluable-induction set (who received at least 1 dose of study medication;had measurable disease at baseline) who were randomized to receive consolidation treatment. Here, 'N' (number of participants analyzed) signifies the participants who had complete response.

Arm/Group Title	Thalidomide + Prednisolone [TP Consolidation]	Bortezomib + Thalidomide + Prednisolone [VTP Consolidation]
Arm/Group Description	Participants who completed induction phase entered in the consolidated treatment phase and received thalidomide 100 mg orally, once daily until disease progression (up to maximum of 12 months) and prednisolone 50 mg orally, on every alternate day until disease progression.	Participants who completed induction phase entered in the consolidated treatment phase and received bortezomib 1.3 mg/m^2 SC every 2 weeks for 32 weeks in addition to thalidomide 100 mg orally, once daily for a maximum of 12 months or until disease progression and prednisolone 50 mg orally, on every alternate day until disease progression.
Measure Participants	56	62
Median (95% Confidence Interval) [months]	18.53	13.37

6. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time between randomization and death. Death of a participant regardless of the cause was considered as an event.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

All randomized analysis set was defined as participants in the all enrolled set (all participants with a non-missing informed consent date and were not screen failures) who were randomized to receive consolidation treatment.

Arm/Group Title	Thalidomide + Prednisolone [TP Consolidation]	Bortezomib + Thalidomide + Prednisolone [VTP Consolidation]
Arm/Group Description	Participants who completed induction phase entered in the consolidated treatment phase and received thalidomide 100 mg orally, once daily until disease progression (up to maximum of 12 months) and prednisolone 50 mg orally, on every alternate day until disease progression.	Participants who completed induction phase entered in the consolidated treatment phase and received bortezomib 1.3 mg/m^2 SC every 2 weeks for 32 weeks in addition to thalidomide 100 mg orally, once daily for a maximum of 12 months or until disease progression and prednisolone 50 mg orally, on every alternate day until disease progression.
Measure Participants	100	103
Median (95% Confidence Interval) [months]	NA	NA

7. Secondary Outcome

Title	Consolidation Phase: Change From Baseline in AQOL-6D Scores at the End of the Consolidation Phase
Description	The assessment of quality of life-6D (AQoL-6D) is a multi-attribute health-related quality of life instrument (QoL). It comprises dimension scores for independent living, relationships, mental health, coping, pain, senses, and utility score for AQol-6D. Each scale ranges between 1 (best QoL) and -0.04 (worst possible QoL).
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

All treated randomized analysis set was defined as participants in the all enrolled set (participants with non-missing informed consent date,not screen failures) received at least 1 dose of any study drug and randomized to receive consolidation treatment. Here, 'N'(number of participants analyzed) participants who were evaluable for this endpoint.

Arm/Group Title	Thalidomide + Prednisolone [TP Consolidation]	Bortezomib + Thalidomide + Prednisolone [VTP Consolidation]
Arm/Group Description	Participants who completed induction phase entered in the consolidated treatment phase and received thalidomide 100 mg orally, once daily until disease progression (up to maximum of 12 months) and prednisolone 50 mg orally, on every alternate day until disease progression.	Participants who completed induction phase entered in the consolidated treatment phase and received bortezomib 1.3 mg/m^2 SC every 2 weeks for 32 weeks in addition to thalidomide 100 mg orally, once daily for a maximum of 12 months or until disease progression and prednisolone 50 mg orally, on every alternate day until disease progression.
Measure Participants	83	86
Independent Living	0.15 (0.335)	0.14 (0.397)
Relationships	0.06 (0.300)	0.05 (0.296)
Mental Health	0.18 (0.319)	0.18 (0.270)
Coping	0.08 (0.278)	0.05 (0.237)
Pain	0.20 (0.373)	0.20 (0.395)
Senses	0.03 (0.140)	0.00 (0.137)
AQoL-6D Utility score	0.11 (0.216)	0.11 (0.213)

8. Secondary Outcome

Title	Consolidation Phase: Change From Baseline in FACT/GOG-NTX Total Score at the End of the Consolidation Phase
Description	Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX) consists of 10 items and evaluates symptoms and concerns associated specifically with chemotherapy-induced neuropathy. 1 FACT/GOG-NTX total score has a range of 0 to 108 with a higher score indicating better quality of life.
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

All treated randomized analysis set was defined as participants in the all enrolled set (participants with non-missing informed consent date,not screen failures) received at least 1 dose of any study drug and randomized to receive consolidation treatment. Here, 'N'(number of participants analyzed) participants who were evaluable for this endpoint.

Arm/Group Title	Thalidomide + Prednisolone [TP Consolidation]	Bortezomib + Thalidomide + Prednisolone [VTP Consolidation]
Arm/Group Description	Participants who completed induction phase entered in the consolidated treatment phase and received thalidomide 100 mg orally, once daily until disease progression (up to maximum of 12 months) and prednisolone 50 mg orally, on every alternate day until disease progression.	Participants who completed induction phase entered in the consolidated treatment phase and received bortezomib 1.3 mg/m^2 SC every 2 weeks for 32 weeks in addition to thalidomide 100 mg orally, once daily for a maximum of 12 months or until disease progression and prednisolone 50 mg orally, on every alternate day until disease progression.
Measure Participants	83	86
Mean (Standard Deviation) [units on a scale]	2.9 (19.68)	1.0 (19.69)

Adverse Events

Adverse Event Reporting Description	Safety population included all participants in the induction and consolidation phase who received at least 1 dose of study drug.
Arm/Group Title	Bortezomib + Cyclophosphamide + Dexamethasone (VCD Induction)		Thalidomide + Prednisolone (TP Consolidation)		Bortezomib + Thalidomide + Prednisolone (VTP Consolidation)
Arm/Group Description	Participants received bortezomib (Velcade) 1.3 milligram per square meter (mg/m^2) subcutaneously (SC) on Days 1, 4, 8, and 11; cyclophosphamide 300 mg/m^2 orally on Days 1, 8, and 15; and dexamethasone 20 milligram (mg) orally on Days 1, 2, 4, 5, 8, 9, 11, and 12 in three 21-day treatment cycles. Participants who completed induction phase entered into the consolidation treatment phase.		Participants who completed induction phase entered in the consolidated treatment phase and received thalidomide 100 mg orally, once daily until disease progression (up to maximum of 12 months) and prednisolone 50 mg orally, on every alternate day until disease progression.		Participants who completed induction phase entered in the consolidated treatment phase and received bortezomib 1.3 mg/m^2 SC every 2 weeks for 32 weeks in addition to thalidomide 100 mg orally, once daily for a maximum of 12 months or until disease progression and prednisolone 50 mg orally, on every alternate day until disease progression.
All Cause Mortality
	Bortezomib + Cyclophosphamide + Dexamethasone (VCD Induction)		Thalidomide + Prednisolone (TP Consolidation)		Bortezomib + Thalidomide + Prednisolone (VTP Consolidation)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Bortezomib + Cyclophosphamide + Dexamethasone (VCD Induction)		Thalidomide + Prednisolone (TP Consolidation)		Bortezomib + Thalidomide + Prednisolone (VTP Consolidation)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	88/254 (34.6%)		22/99 (22.2%)		28/103 (27.2%)
Blood and lymphatic system disorders
Febrile Neutropenia	11/254 (4.3%)		0/99 (0%)		0/103 (0%)
Cardiac disorders
Arrhythmia	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Atrial Fibrillation	1/254 (0.4%)		1/99 (1%)		0/103 (0%)
Atrial Flutter	0/254 (0%)		0/99 (0%)		1/103 (1%)
Left Ventricular Dysfunction	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Sinus Bradycardia	0/254 (0%)		0/99 (0%)		1/103 (1%)
Supraventricular Tachycardia	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Eye disorders
Blepharitis	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Gastrointestinal disorders
Abdominal Pain Lower	0/254 (0%)		1/99 (1%)		0/103 (0%)
Colitis	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Constipation	2/254 (0.8%)		0/99 (0%)		0/103 (0%)
Diarrhoea	1/254 (0.4%)		1/99 (1%)		1/103 (1%)
Gastritis	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Gastrointestinal Haemorrhage	1/254 (0.4%)		0/99 (0%)		1/103 (1%)
Oesophageal Spasm	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Rectal Haemorrhage	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Vomiting	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
General disorders
Adverse Drug Reaction	2/254 (0.8%)		0/99 (0%)		0/103 (0%)
Asthenia	2/254 (0.8%)		0/99 (0%)		0/103 (0%)
Malaise	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Non-Cardiac Chest Pain	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Pyrexia	12/254 (4.7%)		1/99 (1%)		3/103 (2.9%)
Hepatobiliary disorders
Cholecystitis	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Immune system disorders
Drug Hypersensitivity	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Infections and infestations
Anal Abscess	0/254 (0%)		0/99 (0%)		1/103 (1%)
Bacillus Infection	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Cellulitis	1/254 (0.4%)		0/99 (0%)		1/103 (1%)
Device Related Sepsis	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Diverticulitis	0/254 (0%)		1/99 (1%)		1/103 (1%)
Gastroenteritis	1/254 (0.4%)		1/99 (1%)		0/103 (0%)
Hepatitis B	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Herpes Zoster	0/254 (0%)		2/99 (2%)		2/103 (1.9%)
Herpes Zoster Disseminated	0/254 (0%)		1/99 (1%)		0/103 (0%)
Infection	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Influenza	0/254 (0%)		1/99 (1%)		0/103 (0%)
Lobar Pneumonia	1/254 (0.4%)		2/99 (2%)		0/103 (0%)
Localised Infection	0/254 (0%)		1/99 (1%)		0/103 (0%)
Lower Respiratory Tract Infection	4/254 (1.6%)		1/99 (1%)		2/103 (1.9%)
Lung Infection	2/254 (0.8%)		0/99 (0%)		0/103 (0%)
Nocardiosis	0/254 (0%)		0/99 (0%)		1/103 (1%)
Pharyngitis	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Pneumonia	5/254 (2%)		6/99 (6.1%)		7/103 (6.8%)
Pneumonia Influenzal	0/254 (0%)		0/99 (0%)		1/103 (1%)
Pneumonia Primary Atypical	0/254 (0%)		1/99 (1%)		0/103 (0%)
Respiratory Tract Infection	1/254 (0.4%)		2/99 (2%)		1/103 (1%)
Rhinovirus Infection	0/254 (0%)		0/99 (0%)		2/103 (1.9%)
Sepsis	4/254 (1.6%)		1/99 (1%)		0/103 (0%)
Staphylococcal Sepsis	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Subcutaneous Abscess	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Upper Respiratory Tract Infection	2/254 (0.8%)		0/99 (0%)		0/103 (0%)
Viral Infection	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Injury, poisoning and procedural complications
Laceration	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Lumbar Vertebral Fracture	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Rib Fracture	2/254 (0.8%)		0/99 (0%)		0/103 (0%)
Road Traffic Accident	0/254 (0%)		0/99 (0%)		1/103 (1%)
Spinal Compression Fracture	2/254 (0.8%)		0/99 (0%)		0/103 (0%)
Spinal Fracture	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Subdural Haemorrhage	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Thoracic Vertebral Fracture	0/254 (0%)		0/99 (0%)		1/103 (1%)
Investigations
Cytomegalovirus Test Positive	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Metabolism and nutrition disorders
Dehydration	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Hyponatraemia	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/254 (0%)		0/99 (0%)		1/103 (1%)
Back Pain	4/254 (1.6%)		2/99 (2%)		0/103 (0%)
Bone Pain	2/254 (0.8%)		0/99 (0%)		0/103 (0%)
Muscular Weakness	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Osteolysis	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Pathological Fracture	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous Cell Carcinoma	0/254 (0%)		0/99 (0%)		1/103 (1%)
Thyroid Cancer	0/254 (0%)		0/99 (0%)		1/103 (1%)
Transitional Cell Carcinoma	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Nervous system disorders
Convulsion	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Embolic Stroke	0/254 (0%)		1/99 (1%)		0/103 (0%)
Lethargy	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Neuralgia	0/254 (0%)		1/99 (1%)		0/103 (0%)
Spinal Cord Compression	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Renal and urinary disorders
Renal Failure Acute	2/254 (0.8%)		1/99 (1%)		0/103 (0%)
Renal Impairment	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Diaphragmatic Paralysis	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Organising Pneumonia	0/254 (0%)		1/99 (1%)		0/103 (0%)
Pneumonitis	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Pneumothorax	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Pulmonary Embolism	2/254 (0.8%)		1/99 (1%)		2/103 (1.9%)
Pulmonary Hypertension	0/254 (0%)		0/99 (0%)		1/103 (1%)
Respiratory Distress	0/254 (0%)		1/99 (1%)		0/103 (0%)
Respiratory Failure	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Skin and subcutaneous tissue disorders
Decubitus Ulcer	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Drug Eruption	3/254 (1.2%)		0/99 (0%)		0/103 (0%)
Rash	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Vascular disorders
Circulatory Collapse	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Deep Vein Thrombosis	1/254 (0.4%)		1/99 (1%)		0/103 (0%)
Embolism	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Embolism Venous	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Hypotension	2/254 (0.8%)		0/99 (0%)		0/103 (0%)
Orthostatic Hypotension	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Peripheral Ischaemia	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Vasculitis	1/254 (0.4%)		0/99 (0%)		0/103 (0%)
Other (Not Including Serious) Adverse Events
	Bortezomib + Cyclophosphamide + Dexamethasone (VCD Induction)		Thalidomide + Prednisolone (TP Consolidation)		Bortezomib + Thalidomide + Prednisolone (VTP Consolidation)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	233/254 (91.7%)		95/99 (96%)		96/103 (93.2%)
Blood and lymphatic system disorders
Anaemia	25/254 (9.8%)		1/99 (1%)		3/103 (2.9%)
Neutropenia	17/254 (6.7%)		0/99 (0%)		5/103 (4.9%)
Ear and labyrinth disorders
Tinnitus	2/254 (0.8%)		5/99 (5.1%)		8/103 (7.8%)
Endocrine disorders
Cushingoid	0/254 (0%)		6/99 (6.1%)		3/103 (2.9%)
Eye disorders
Vision Blurred	8/254 (3.1%)		8/99 (8.1%)		7/103 (6.8%)
Visual Impairment	1/254 (0.4%)		6/99 (6.1%)		2/103 (1.9%)
Gastrointestinal disorders
Constipation	91/254 (35.8%)		38/99 (38.4%)		29/103 (28.2%)
Diarrhoea	32/254 (12.6%)		14/99 (14.1%)		15/103 (14.6%)
Dry Mouth	6/254 (2.4%)		4/99 (4%)		6/103 (5.8%)
Dyspepsia	14/254 (5.5%)		3/99 (3%)		1/103 (1%)
Nausea	82/254 (32.3%)		10/99 (10.1%)		12/103 (11.7%)
Vomiting	32/254 (12.6%)		7/99 (7.1%)		3/103 (2.9%)
General disorders
Chest Pain	9/254 (3.5%)		5/99 (5.1%)		2/103 (1.9%)
Fatigue	61/254 (24%)		18/99 (18.2%)		16/103 (15.5%)
Injection Site Rash	14/254 (5.5%)		0/99 (0%)		1/103 (1%)
Injection Site Reaction	19/254 (7.5%)		0/99 (0%)		7/103 (6.8%)
Oedema Peripheral	44/254 (17.3%)		15/99 (15.2%)		16/103 (15.5%)
Infections and infestations
Herpes Zoster	8/254 (3.1%)		10/99 (10.1%)		5/103 (4.9%)
Lower Respiratory Tract Infection	4/254 (1.6%)		5/99 (5.1%)		6/103 (5.8%)
Nasopharyngitis	5/254 (2%)		5/99 (5.1%)		10/103 (9.7%)
Upper Respiratory Tract Infection	29/254 (11.4%)		32/99 (32.3%)		39/103 (37.9%)
Injury, poisoning and procedural complications
Contusion	4/254 (1.6%)		6/99 (6.1%)		3/103 (2.9%)
Investigations
Weight Increased	7/254 (2.8%)		26/99 (26.3%)		17/103 (16.5%)
Metabolism and nutrition disorders
Decreased Appetite	19/254 (7.5%)		1/99 (1%)		3/103 (2.9%)
Hyperglycaemia	12/254 (4.7%)		6/99 (6.1%)		5/103 (4.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	13/254 (5.1%)		6/99 (6.1%)		7/103 (6.8%)
Back Pain	24/254 (9.4%)		9/99 (9.1%)		12/103 (11.7%)
Muscle Spasms	6/254 (2.4%)		9/99 (9.1%)		11/103 (10.7%)
Muscular Weakness	5/254 (2%)		5/99 (5.1%)		4/103 (3.9%)
Musculoskeletal Chest Pain	14/254 (5.5%)		2/99 (2%)		3/103 (2.9%)
Pain in Extremity	13/254 (5.1%)		7/99 (7.1%)		7/103 (6.8%)
Nervous system disorders
Dizziness	23/254 (9.1%)		7/99 (7.1%)		7/103 (6.8%)
Dysgeusia	21/254 (8.3%)		2/99 (2%)		0/103 (0%)
Headache	21/254 (8.3%)		8/99 (8.1%)		5/103 (4.9%)
Hypoaesthesia	10/254 (3.9%)		6/99 (6.1%)		6/103 (5.8%)
Lethargy	16/254 (6.3%)		3/99 (3%)		6/103 (5.8%)
Neuralgia	19/254 (7.5%)		14/99 (14.1%)		16/103 (15.5%)
Neuropathy Peripheral	34/254 (13.4%)		24/99 (24.2%)		30/103 (29.1%)
Paraesthesia	11/254 (4.3%)		7/99 (7.1%)		9/103 (8.7%)
Peripheral Sensory Neuropathy	62/254 (24.4%)		38/99 (38.4%)		38/103 (36.9%)
Tremor	12/254 (4.7%)		11/99 (11.1%)		11/103 (10.7%)
Psychiatric disorders
Insomnia	56/254 (22%)		22/99 (22.2%)		13/103 (12.6%)
Mood Altered	9/254 (3.5%)		5/99 (5.1%)		5/103 (4.9%)
Respiratory, thoracic and mediastinal disorders
Cough	14/254 (5.5%)		8/99 (8.1%)		15/103 (14.6%)
Dyspnoea	16/254 (6.3%)		7/99 (7.1%)		6/103 (5.8%)
Dyspnoea Exertional	7/254 (2.8%)		3/99 (3%)		6/103 (5.8%)
Skin and subcutaneous tissue disorders
Rash	22/254 (8.7%)		7/99 (7.1%)		10/103 (9.7%)
Vascular disorders
Hypertension	2/254 (0.8%)		6/99 (6.1%)		4/103 (3.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.