Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma (PANORAMA-1)

• ClinicalTrials.gov Identifier: NCT01023308
• Recruitment Status: Completed
• First Posted: December 2, 2009
• Results First Posted: October 23, 2015
• Last Update Posted: March 17, 2020
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Multiple Myeloma
• Interventions: Drug: Panobinostat; Drug: Bortezomib; Drug: Dexamethasone; Drug: Placebo
• Enrollment: 767

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Panobinostat + Bortezomib	Placebo + Bortezomib
Arm/Group Description	Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
Period Title: Overall Study
Started	387	381
Completed	102 [1]	102 [1]
Not Completed	285	279
Reason Not Completed
Abnormal test proceedure results	3	8
Administrative problems	2	1
Adverse Event	130	66
Death	21	17
Disease progression	82	153
New Cancer therapy	4	7
Protocol Violation	3	4
Untreated	5	5
Lost to Follow-up	1	0
Withdrawal by Subject	34	18
[1] completed all planned cycles of study treatment as per protocol

Baseline Characteristics

Arm/Group Title		Panobinostat + Bortezomib	Placebo + Bortezomib	Total
Arm/Group Description		Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.	Total of all reporting groups
Overall Number of Baseline Participants		387	381	768
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	387 participants	381 participants	768 participants
		62.4 (9.34)	61.8 (9.43)	62.1 (9.38)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	387 participants	381 participants	768 participants
	Female	185 47.8%	176 46.2%	361 47.0%
	Male	202 52.2%	205 53.8%	407 53.0%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	387 participants	381 participants	768 participants
Caucasian		249	250	499
Asian		128	104	232
Black		5	17	22
Other		5	10	15

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival Events in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone.
Description	[Not Specified]
Time Frame	45 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Panobinostat + Bortezomib	Placebo + Bortezomib
Arm/Group Description:	Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
Overall Number of Participants Analyzed	387	381
Measure Type: Number; Unit of Measure: number of events
	207	260

2. Primary Outcome

Title	Progression Free Survival in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone.
Description	[Not Specified]
Time Frame	45 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Panobinostat + Bortezomib	Placebo + Bortezomib
Arm/Group Description:	Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
Overall Number of Participants Analyzed	387	381
Median (95% Confidence Interval); Unit of Measure: months
	11.99; (10.32 to 12.94)	8.80; (7.56 to 9.23)

3. Secondary Outcome

Title	Overall Survival in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone
Description	Number of OS events
Time Frame	45 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Panobinostat + Bortezomib	Placebo + Bortezomib
Arm/Group Description:	Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
Overall Number of Participants Analyzed	387	381
Measure Type: Number; Unit of Measure: Number of OS events
	134	152

4. Secondary Outcome

Title	Overall Survival in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone
Description	survival time in months
Time Frame	45 months

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Panobinostat + Bortezomib	Placebo + Bortezomib
Arm/Group Description:	Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
Overall Number of Participants Analyzed	387	381
Median (95% Confidence Interval); Unit of Measure: months
	40.28; (35.02 to 44.81)	35.78; (28.98 to 40.64)

5. Secondary Outcome

Title	Overall Response Rate in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone.
Description	Best overall response based on mEBMT criteria per investigator assessment
Time Frame	45 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Panobinostat + Bortezomib	Placebo + Bortezomib
Arm/Group Description:	Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
Overall Number of Participants Analyzed	387	381
Measure Type: Number; Unit of Measure: % participants with response
	60.7	54.6

6. Secondary Outcome

Title	Time to Response Per Investigator Assessment (mEBMT Criteria) of Response Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone.
Description	[Not Specified]
Time Frame	45 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Panobinostat + Bortezomib	Placebo + Bortezomib
Arm/Group Description:	Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
Overall Number of Participants Analyzed	387	381
Median (95% Confidence Interval); Unit of Measure: time to response in months
	1.51; (1.41 to 1.64)	2.00; (1.61 to 2.79)

7. Secondary Outcome

Title	Duration of Response Per Investigator Assessment (mEBMT Criteria) Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone.
Description	[Not Specified]
Time Frame	45 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Panobinostat + Bortezomib	Placebo + Bortezomib
Arm/Group Description:	Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
Overall Number of Participants Analyzed	387	381
Median (95% Confidence Interval); Unit of Measure: duration of response in months
	13.14; (11.76 to 14.92)	10.87; (9.23 to 11.76)

8. Secondary Outcome

Title	Time to Progression/Relapse Per Investigator Assessment (mEBMT Criteria) Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone.
Description	[Not Specified]
Time Frame	45 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Panobinostat + Bortezomib	Placebo + Bortezomib
Arm/Group Description:	Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
Overall Number of Participants Analyzed	387	381
Median (95% Confidence Interval); Unit of Measure: months
	12.71; (11.30 to 14.06)	8.54; (7.66 to 9.72)

9. Secondary Outcome

Title	European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC) QLQ-MY20-Change From Baseline by Treatment Group
Description	Higher values in the disease symptoms and side effects of treatment scores indicate worsening. Higher scores in the future perspective and body image scores indicate improvement. LS Means and SEM are estimated from the repeated measures model. Following factors and covariates are included in the repeated measurement model: time, treatment, treatment by time interaction, number of prior lines of anti-MM therapy (1/ 2 and 3), prior use of BTZ (Yes/ No), baseline score.Disease Symptom is the sum of 20 questions, total score ranges from 0 (best possible outcome) to 100 (worst possible outcome)", All subscales of EORTC QLQ-MY20 have the same score range of 0 -100. Decrease in symptom scores from baseline indicate improvement in symptoms.
Time Frame	12, 24 and 48 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Panobinostat + Bortezomib	Placebo + Bortezomib
Arm/Group Description:	Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
Overall Number of Participants Analyzed	387	381
Least Squares Mean (95% Confidence Interval); Unit of Measure: score on a scale
Disease Symptom wk 12 change baseline (n=215,243)	-4.795; (-6.76 to -2.83)	-4.865; (-6.75 to -2.98)
Disease Symptom wk 24 change baseline (n=148,177)	-4.401; (-6.53 to -2.27)	-6.797; (-8.79 to -4.81)
Disease Symptom wk 48 change baseline (n=37,26)	-2.836; (-6.76 to -1.084)	-6.626; (-11.1 to -2.12)
Side effects of treatment wk 12 chge (n=213,242)	8.162; (6.510 to 9.814)	5.524; (3.933 to 7.115)
Side effects of treatment wk 24 chge (n=148,175)	9.016; (6.955 to 11.08)	7.731; (5.795 to 9.668)
Side effects of treatment wk 48 chge (n=37,26)	3.357; (0.442 to 6.273)	3.654; (0.352 to 6.956)
Future perspective wk 12 chge (n=214,242)	5.319; (2.893 to 7.744)	6.194; (3.854 to 8.533)
Future perspective wk 24 chge (n=148,176)	3.877; (0.977 to 6.778)	5.839; (3.103 to 8.575)
Future perspective wk 48 chge (n=37,26)	4.331; (-.142 to 8.804)	6.951; (1.807 to 12.10)
Body image wk 12 chge (n=213,240)	-7.178; (-10.5 to -3.87)	-6.22; (-9.41 to -3.03)
Body image wk 24 chge (n=147,175)	-11.463; (-15.3 to -7.66)	-7.358; (-10.9 to -3.81)
Body image wk 48 chge (n=37,26)	-2.161; (-7.73 to 3.410)	-4.666; (-11.1 to 1.729)

10. Secondary Outcome

Title	European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group
Description	The EORTC QLQ-C30 measures functional dimensions (physical, role, emotional, cognitive, and social), three multi-item symptom scales (fatigue, nausea/vomiting, and pain), six single-item symptom scales (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea and financial impact) and a global health status/QoL scale. Disease Symptom is the sum of 30 questions, total score ranges from 0 (best possible outcome) to 100 (worst possible outcome)", All subscales of EORTC QLQ-C30 have the same score range of 0 -100. For global health status and other functional scales,an increase from baseline indicates improvement of QoL. Whereas for symptoms scales, fatigue, dyspnea, insomnia, appetite loss, constipation and diarrhea, decrease in scores from baseline indicate improvement in symptoms.
Time Frame	12, 24 and 48 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Panobinostat + Bortezomib	Placebo + Bortezomib
Arm/Group Description:	Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
Overall Number of Participants Analyzed	387	381
Least Squares Mean (95% Confidence Interval); Unit of Measure: score on a scale
Global health wk 12 change baseline (n=216,239)	-9.853; (-12.50 to -7.20)	-4.044; (-6.60 to -1.49)
Global health wk 24 change baseline (n=150,176)	-7.867; (-10.7 to -5.08)	-1.518; (-4.11 to -1.075)
Global health wk 48 change baseline (n=38,26)	-2.986; (-7.21 to 1.237)	4.345; (-0.416 to 9.106)
Physical functioning wk 12 chge (n=217,242)	-9.67; (-12.00 to -7.38)	-5.393; (-76.3 to -3.16)
Physical functioning wk 24 chge (n=151,177)	-9.516; (-12.20 to -7.38)	-6.456; (-8.98 to -3.93)
Physical functioning wk 48 chge (n=38,26)	-2.88; (-6.41 to 0.651)	2.037; (-2.07 to 6.147)
Role functioning wk 12 chge (n=215,237)	-11.159; (-14.6 to -7.74)	-6.762; (-10.1 to -3.45)
Role functioning wk 24 chge (n=150,176)	-11.875; (-15.7 to -8.01)	-11.263; (-14.9 to -7.61)
Role functioning wk 48 chge (n=38,26)	-5.927; (-11.4 to -0.424)	-0.401; (-6.73 to 5.924)
Cognitive functioning wk 12 chge (n=216,240)	-4.464; (-6.89 to -2.04)	-1.023; (-3.36 to 1.318)
Cognitive functioning wk 24 chge (n=149,176)	-6.053; (-8.87 to -3.24)	-3.542; (-6.22 to -0.865)
Cognitive functioning wk 48 chge (n=38,26)	-5.568; (-9.79 to -1.34)	-4.042; (-8.99 to 0.902)
Social functioning wk 12 chge (n=216,240)	-8.502; (-11.6 to -5.44)	-3.991; (-6.97 to 1.02)
Social functioning wk 24 chge (n=148,171)	-8.925; (-12.4 to -5.42)	-6.338; (-9.66 to -3.02)
Social functioning wk 48 chge (n=37,26)	-6.104; (-11.0 to -1.22)	4.617; (-0.930 to 10.16)
Fatigue wk 12 chge (n=217,241)	15.122; (12.27 to 17.98)	7.939; (5.174 to 10.70)
Fatigue wk 24 chge (n=151,176)	12.677; (9.419 to 15.94)	9.203; (6.136 to 12.27)
Fatigue wk 48 chge(n=38,26)	4.646; (0.086 to 9.206)	-2.625; (-7.88 to 2.628)
Dyspnea wk 12 chge (n=217,240)	13.964; (10.60 to 17.33)	6.266; (3.012 to 9.521)
Dyspnea wk 24 chge (n=151,177)	7.939; (4.639 to 11.24)	5.308; (2.221 to 8.394)
Dyspnea wk 48 chge (n=38,26)	4.118; (-1.58 to 9.813)	2.82; (-3.88 to 9.523)
Insomnia wk 12 chge (n=216,239)	6.283; (2.851 to 9.715)	7.625; (4.331 to 10.92)
Insomnia wk 24 chge (n=149,176)	10.023; (6.038 to 14.01)	6.104; (2.381 to 9.827)
Insomnia wk 48 chge (n=38,26)	-2.464; (-8.74 to 3.811)	-3.442; (-10.9 to 4.017)
Appetite loss wk 12 chge (n=217,239)	15.167; (11.60 to 18.74)	5.383; (1.925 to 8.841)
Appetite loss wk 24 chge (n=151,176)	16.574; (12.39 to 20.76)	5.861; (1.918 to 9.804)
Appetite loss wk 48 chge (n=38,26)	3.999; (-2.08 to 10.07)	-2.963; (-9.99 to 4.061)
Constipation wk 12 chge (n=215,240)	4.135; (0.667 to 7.603)	6.42; (3.104 to 9.735)
Constipation wk 24 chge (n=151,177)	-0.153; (-3.64 to 3.337)	0.524; (-2.73 to 5.782)
Constipation wk 48 chge (n=38,25)	-0.358; (-5.57 to 4.851)	-0.946; (-7.26 to 5.373)
Diarrhea wk 12 chge (n=217,241)	18.888; (15.04 to 22.74)	10.206; (6.452 to 13.96)
Diarrhea wk 24 chge (n=150,177)	23.163; (18.46 to 27.87)	16.406; (11.98 to 20.83)
Diarrhea wk 48 chge (n=38,26)	20.48; (14.02 to 26.94)	10.996; (3.422 to 18.57)

11. Secondary Outcome

Title	Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System : FACT/GOG-NTX-Change From Baseline by Treatment Group
Description	Chronic Illness Therapy (FACIT) Measurement System and focuses on four general quality of life domains for physical well being, functional well-being, social/family well-being, and emotional well-being, and includes additional items to characterize treatment-related neurotoxicity. Higher subscales/total scores represent higher QOL. In the case of the neurotoxicity subscale, lower scores correspond to higher neurotoxicity. The recall period referenced in the questionnaire is the past 7 days.Ranges for FACT-G subscales are as follows:.PWB, scale 0 -28, , NtxS scale 0-44, FACT/GOG-Ntx trial outcome index scale is 0-100 and FACT-G scale is also scaled 0-100. An increase from baseline in these scores indicate improvement.
Time Frame	12, 24 and 48 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Panobinostat + Bortezomib	Placebo + Bortezomib
Arm/Group Description:	Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day.
Overall Number of Participants Analyzed	387	381
Least Squares Mean (95% Confidence Interval); Unit of Measure: score on a scale
Neurotoxicity wk 12 change baseline (n=212,240)	-4.481; (-5.33 to -3.63)	-3.337; (-4.17 to -2.50)
Neurotoxicity wk 24 change baseline (n=148,174)	-4.564; (-5.49 to -3.64)	-4.739; (-5.61 to -3.86)
Neurotoxicity wk 48 change baseline (n=35,26)	-3.158; (-4.52 to -1.79)	-2.133; (-3.64 to -0.627)
Physical wellbeing wk 12 chge (n=215,240)	-3.29; (-3.94 to -2.64)	-1.952; (-2.58 to -1.32)
Physical wellbeingwk 24 chge (n=150,176)	-3.044; (-3.74 to -2.35)	-2.259; (-2.92 to -1.60)
Physical wellbeing wk 48 chge (n=38,26)	-2.037; (-3.08 to -0.992)	0.203; (-1.03 to 1.439)
Trial Outcomes wk 12 chge (n=209,236)	-10.573; (-12.2 to -8.86)	-6.874; (-8.55 to -5.19)
Trial Outcomes wk 24 chge (n=148,173)	-9.84; (-11.7 to -7.98)	-8.894; (-10.7 to -7.13)
Trial Outcomes wk 48 chge (n=35,26)	-6.633; (-9.28 to -3.98)	-2.821; (-5.76 to 0.122)
FACT-G Total wk 12 chge (n=213,240)	-6.658; (-8.23 to -5.09)	-4.106; (-5.64 to -2.57)
FACT-G Totalwk 24 chge (n=147,175)	-6.076; (-7.84 to -4.31)	-4.609; (-6.30 to -2.92)
FACT-G Total wk 48 chge (n=37,26)	-2.704; (-5.29 to -0.118)	-1.435; (-4.42 to 1.547)
FACT/GOGNTX Total wk 12 chge (n=206,230)	-11.176; (-13.3 to -9.03)	-7.524; (-9.64 to -5.41)
FACT/GOGNTX Total wk 24 chge (n=146,172)	-10.581; (-12.9 to -8.23)	-9.179; (-9.64 to -5.41)
FACT/GOGNTX Total wk 48 chge (n=35,26)	-5.871; (-9.24 to -2.50)	-3.151; (-6.92 to 0.614)

Adverse Events

Time Frame	Safety Set consists of all patients who received at least one dose of any component of the study treatment. 10 patients were randomized but did not receive treatment. 6 patients from PAN+BTZ+Dex and 4 patients from PBO+BTZ+Dex
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	PAN+BTZ	PBO+BTZ
Arm/Group Description	Panobinostat was given 20 mg hard gelatin capsules . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV)injection. Dexamethasone was given as an oral dose of 20 mg/day.	Placebo was given as a hard gelatin capsule in the image of Panobinostat . Bortezomib was given at 1.3 mg/m2 as a 3 to 5 second bolus intravenous (IV) injection. Dexamethasone was given as an oral dose of 20 mg/day..
All-Cause Mortality
	PAN+BTZ	PBO+BTZ
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	PAN+BTZ	PBO+BTZ
	Affected / at Risk (%)	Affected / at Risk (%)
Total	228/381 (59.84%)	157/377 (41.64%)
Blood and lymphatic system disorders
Anaemia † 1	14/381 (3.67%)	3/377 (0.80%)
Febrile neutropenia † 1	3/381 (0.79%)	1/377 (0.27%)
Hyperviscosity syndrome † 1	0/381 (0.00%)	1/377 (0.27%)
Leukocytosis † 1	1/381 (0.26%)	0/377 (0.00%)
Leukopenia † 1	2/381 (0.52%)	0/377 (0.00%)
Monocytosis † 1	1/381 (0.26%)	0/377 (0.00%)
Neutropenia † 1	2/381 (0.52%)	1/377 (0.27%)
Pancytopenia † 1	1/381 (0.26%)	1/377 (0.27%)
Thrombocytopenia † 1	28/381 (7.35%)	8/377 (2.12%)
Cardiac disorders
Acute coronary syndrome † 1	1/381 (0.26%)	0/377 (0.00%)
Acute myocardial infarction † 1	1/381 (0.26%)	0/377 (0.00%)
Angina pectoris † 1	2/381 (0.52%)	2/377 (0.53%)
Atrial fibrillation † 1	4/381 (1.05%)	2/377 (0.53%)
Atrial flutter † 1	0/381 (0.00%)	1/377 (0.27%)
Bradycardia † 1	2/381 (0.52%)	0/377 (0.00%)
Cardiac arrest † 1	2/381 (0.52%)	2/377 (0.53%)
Cardiac failure † 1	1/381 (0.26%)	1/377 (0.27%)
Cardiac failure acute † 1	1/381 (0.26%)	0/377 (0.00%)
Cardiac failure congestive † 1	0/381 (0.00%)	1/377 (0.27%)
Cardio-respiratory arrest † 1	0/381 (0.00%)	1/377 (0.27%)
Cardiopulmonary failure † 1	0/381 (0.00%)	1/377 (0.27%)
Left ventricular dysfunction † 1	0/381 (0.00%)	1/377 (0.27%)
Myocardial infarction † 1	2/381 (0.52%)	0/377 (0.00%)
Myocardial ischaemia † 1	2/381 (0.52%)	0/377 (0.00%)
Pericardial effusion † 1	0/381 (0.00%)	1/377 (0.27%)
Sinus tachycardia † 1	1/381 (0.26%)	0/377 (0.00%)
Tachycardia † 1	2/381 (0.52%)	0/377 (0.00%)
Ventricular tachycardia † 1	1/381 (0.26%)	0/377 (0.00%)
Ear and labyrinth disorders
Vertigo † 1	1/381 (0.26%)	0/377 (0.00%)
Eye disorders
Conjunctivitis † 1	1/381 (0.26%)	0/377 (0.00%)
Exophthalmos † 1	1/381 (0.26%)	0/377 (0.00%)
Optic ischaemic neuropathy † 1	1/381 (0.26%)	0/377 (0.00%)
Gastrointestinal disorders
Abdominal discomfort † 1	1/381 (0.26%)	0/377 (0.00%)
Abdominal distension † 1	1/381 (0.26%)	0/377 (0.00%)
Abdominal pain † 1	3/381 (0.79%)	3/377 (0.80%)
Abdominal pain upper † 1	1/381 (0.26%)	0/377 (0.00%)
Colitis † 1	3/381 (0.79%)	0/377 (0.00%)
Constipation † 1	3/381 (0.79%)	3/377 (0.80%)
Diarrhoea † 1	43/381 (11.29%)	9/377 (2.39%)
Dysphagia † 1	1/381 (0.26%)	0/377 (0.00%)
Faecaloma † 1	1/381 (0.26%)	0/377 (0.00%)
Gastric haemorrhage † 1	2/381 (0.52%)	0/377 (0.00%)
Gastritis † 1	2/381 (0.52%)	0/377 (0.00%)
Gastrointestinal haemorrhage † 1	2/381 (0.52%)	3/377 (0.80%)
Gastrooesophageal reflux disease † 1	1/381 (0.26%)	0/377 (0.00%)
Haematemesis † 1	1/381 (0.26%)	0/377 (0.00%)
Haematochezia † 1	2/381 (0.52%)	0/377 (0.00%)
Haemorrhoids † 1	0/381 (0.00%)	1/377 (0.27%)
Ileus † 1	5/381 (1.31%)	3/377 (0.80%)
Ileus paralytic † 1	0/381 (0.00%)	1/377 (0.27%)
Inguinal hernia † 1	2/381 (0.52%)	1/377 (0.27%)
Intestinal ischaemia † 1	1/381 (0.26%)	0/377 (0.00%)
Large intestine perforation † 1	1/381 (0.26%)	0/377 (0.00%)
Nausea † 1	7/381 (1.84%)	0/377 (0.00%)
Necrotising oesophagitis † 1	1/381 (0.26%)	0/377 (0.00%)
Pancreatitis † 1	1/381 (0.26%)	0/377 (0.00%)
Pancreatitis acute † 1	2/381 (0.52%)	1/377 (0.27%)
Peritoneal necrosis † 1	1/381 (0.26%)	0/377 (0.00%)
Rectal haemorrhage † 1	1/381 (0.26%)	0/377 (0.00%)
Subileus † 1	1/381 (0.26%)	1/377 (0.27%)
Upper gastrointestinal haemorrhage † 1	2/381 (0.52%)	0/377 (0.00%)
Vomiting † 1	12/381 (3.15%)	3/377 (0.80%)
General disorders
Asthenia † 1	15/381 (3.94%)	6/377 (1.59%)
Chest discomfort † 1	1/381 (0.26%)	1/377 (0.27%)
Chills † 1	1/381 (0.26%)	0/377 (0.00%)
Fatigue † 1	11/381 (2.89%)	2/377 (0.53%)
General physical health deterioration † 1	2/381 (0.52%)	0/377 (0.00%)
Generalised oedema † 1	1/381 (0.26%)	0/377 (0.00%)
Hypothermia † 1	0/381 (0.00%)	2/377 (0.53%)
Multi-organ failure † 1	1/381 (0.26%)	1/377 (0.27%)
Non-cardiac chest pain † 1	1/381 (0.26%)	3/377 (0.80%)
Oedema peripheral † 1	1/381 (0.26%)	0/377 (0.00%)
Pyrexia † 1	16/381 (4.20%)	11/377 (2.92%)
Spinal pain † 1	0/381 (0.00%)	1/377 (0.27%)
Sudden death † 1	1/381 (0.26%)	1/377 (0.27%)
Hepatobiliary disorders
Biliary dyskinesia † 1	0/381 (0.00%)	1/377 (0.27%)
Cholecystitis † 1	1/381 (0.26%)	1/377 (0.27%)
Hepatic cirrhosis † 1	1/381 (0.26%)	0/377 (0.00%)
Hepatic failure † 1	1/381 (0.26%)	0/377 (0.00%)
Hepatomegaly † 1	1/381 (0.26%)	1/377 (0.27%)
Hyperbilirubinaemia † 1	0/381 (0.00%)	1/377 (0.27%)
Jaundice † 1	0/381 (0.00%)	1/377 (0.27%)
Infections and infestations
Acute tonsillitis † 1	1/381 (0.26%)	0/377 (0.00%)
Appendicitis † 1	1/381 (0.26%)	0/377 (0.00%)
Aspergillosis † 1	1/381 (0.26%)	0/377 (0.00%)
Atypical pneumonia † 1	1/381 (0.26%)	0/377 (0.00%)
Bacteraemia † 1	0/381 (0.00%)	1/377 (0.27%)
Bacteriuria † 1	1/381 (0.26%)	0/377 (0.00%)
Bronchitis † 1	3/381 (0.79%)	2/377 (0.53%)
Bronchopneumonia † 1	1/381 (0.26%)	1/377 (0.27%)
Bronchopulmonary aspergillosis † 1	1/381 (0.26%)	0/377 (0.00%)
Cellulitis † 1	2/381 (0.52%)	1/377 (0.27%)
Clostridium difficile colitis † 1	2/381 (0.52%)	0/377 (0.00%)
Cytomegalovirus colitis † 1	1/381 (0.26%)	0/377 (0.00%)
Device related infection † 1	0/381 (0.00%)	1/377 (0.27%)
Device related sepsis † 1	1/381 (0.26%)	0/377 (0.00%)
Disseminated tuberculosis † 1	1/381 (0.26%)	0/377 (0.00%)
Diverticulitis † 1	1/381 (0.26%)	0/377 (0.00%)
Enteritis infectious † 1	1/381 (0.26%)	0/377 (0.00%)
Erysipelas † 1	0/381 (0.00%)	1/377 (0.27%)
Escherichia urinary tract infection † 1	0/381 (0.00%)	1/377 (0.27%)
Gastroenteritis † 1	7/381 (1.84%)	2/377 (0.53%)
Gastroenteritis salmonella † 1	2/381 (0.52%)	0/377 (0.00%)
Gastrointestinal infection † 1	1/381 (0.26%)	0/377 (0.00%)
Haemophilus sepsis † 1	0/381 (0.00%)	1/377 (0.27%)
Hepatitis B † 1	3/381 (0.79%)	1/377 (0.27%)
Herpes zoster † 1	4/381 (1.05%)	5/377 (1.33%)
Infection † 1	5/381 (1.31%)	2/377 (0.53%)
Influenza † 1	1/381 (0.26%)	1/377 (0.27%)
Lobar pneumonia † 1	2/381 (0.52%)	0/377 (0.00%)
Lower respiratory tract infection † 1	3/381 (0.79%)	3/377 (0.80%)
Lung infection † 1	2/381 (0.52%)	2/377 (0.53%)
Nasopharyngitis † 1	0/381 (0.00%)	1/377 (0.27%)
Necrotising fasciitis † 1	0/381 (0.00%)	2/377 (0.53%)
Neutropenic sepsis † 1	2/381 (0.52%)	1/377 (0.27%)
Oral candidiasis † 1	0/381 (0.00%)	1/377 (0.27%)
Parotitis † 1	1/381 (0.26%)	0/377 (0.00%)
Periodontitis † 1	1/381 (0.26%)	0/377 (0.00%)
Pharyngitis † 1	2/381 (0.52%)	1/377 (0.27%)
Pneumococcal sepsis † 1	1/381 (0.26%)	0/377 (0.00%)
Pneumonia † 1	56/381 (14.70%)	40/377 (10.61%)
Pneumonia bacterial † 1	0/381 (0.00%)	2/377 (0.53%)
Pneumonia fungal † 1	2/381 (0.52%)	0/377 (0.00%)
Pneumonia haemophilus † 1	0/381 (0.00%)	1/377 (0.27%)
Pneumonia influenzal † 1	2/381 (0.52%)	1/377 (0.27%)
Pneumonia pneumococcal † 1	0/381 (0.00%)	1/377 (0.27%)
Pneumonia respiratory syncytial viral † 1	0/381 (0.00%)	1/377 (0.27%)
Pseudomonal bacteraemia † 1	1/381 (0.26%)	0/377 (0.00%)
Pulmonary tuberculosis † 1	1/381 (0.26%)	1/377 (0.27%)
Respiratory tract infection † 1	4/381 (1.05%)	2/377 (0.53%)
Salmonellosis † 1	0/381 (0.00%)	1/377 (0.27%)
Sepsis † 1	9/381 (2.36%)	7/377 (1.86%)
Septic shock † 1	9/381 (2.36%)	2/377 (0.53%)
Sinusitis † 1	1/381 (0.26%)	1/377 (0.27%)
Skin infection † 1	1/381 (0.26%)	0/377 (0.00%)
Staphylococcal sepsis † 1	0/381 (0.00%)	1/377 (0.27%)
Streptococcal sepsis † 1	0/381 (0.00%)	1/377 (0.27%)
Upper respiratory tract infection † 1	4/381 (1.05%)	3/377 (0.80%)
Urinary tract infection † 1	8/381 (2.10%)	4/377 (1.06%)
Varicella † 1	1/381 (0.26%)	0/377 (0.00%)
Viral haemorrhagic cystitis † 1	0/381 (0.00%)	1/377 (0.27%)
Viral infection † 1	1/381 (0.26%)	0/377 (0.00%)
Injury, poisoning and procedural complications
Ankle fracture † 1	1/381 (0.26%)	0/377 (0.00%)
Contusion † 1	0/381 (0.00%)	1/377 (0.27%)
Fall † 1	2/381 (0.52%)	0/377 (0.00%)
Femoral neck fracture † 1	1/381 (0.26%)	1/377 (0.27%)
Femur fracture † 1	0/381 (0.00%)	1/377 (0.27%)
Hand fracture † 1	1/381 (0.26%)	0/377 (0.00%)
Humerus fracture † 1	0/381 (0.00%)	1/377 (0.27%)
Intentional overdose † 1	1/381 (0.26%)	0/377 (0.00%)
Laceration † 1	1/381 (0.26%)	0/377 (0.00%)
Overdose † 1	3/381 (0.79%)	0/377 (0.00%)
Pelvic fracture † 1	1/381 (0.26%)	0/377 (0.00%)
Rib fracture † 1	0/381 (0.00%)	1/377 (0.27%)
Tibia fracture † 1	1/381 (0.26%)	0/377 (0.00%)
Transfusion reaction † 1	1/381 (0.26%)	0/377 (0.00%)
Investigations
Alanine aminotransferase increased † 1	1/381 (0.26%)	1/377 (0.27%)
Aspartate aminotransferase increased † 1	1/381 (0.26%)	1/377 (0.27%)
Blood creatinine increased † 1	1/381 (0.26%)	2/377 (0.53%)
Blood lactate dehydrogenase increased † 1	0/381 (0.00%)	1/377 (0.27%)
Blood potassium decreased † 1	0/381 (0.00%)	1/377 (0.27%)
Blood pressure decreased † 1	0/381 (0.00%)	1/377 (0.27%)
C-reactive protein increased † 1	2/381 (0.52%)	0/377 (0.00%)
Gamma-glutamyltransferase increased † 1	0/381 (0.00%)	2/377 (0.53%)
General physical condition abnormal † 1	1/381 (0.26%)	0/377 (0.00%)
Platelet count decreased † 1	4/381 (1.05%)	0/377 (0.00%)
Weight decreased † 1	0/381 (0.00%)	1/377 (0.27%)
White blood cell count decreased † 1	1/381 (0.26%)	0/377 (0.00%)
Metabolism and nutrition disorders
Acidosis † 1	0/381 (0.00%)	1/377 (0.27%)
Decreased appetite † 1	4/381 (1.05%)	2/377 (0.53%)
Dehydration † 1	11/381 (2.89%)	5/377 (1.33%)
Diabetes mellitus † 1	0/381 (0.00%)	1/377 (0.27%)
Diabetes mellitus inadequate control † 1	1/381 (0.26%)	0/377 (0.00%)
Electrolyte imbalance † 1	1/381 (0.26%)	0/377 (0.00%)
Hypercalcaemia † 1	1/381 (0.26%)	3/377 (0.80%)
Hyperglycaemia † 1	2/381 (0.52%)	3/377 (0.80%)
Hypocalcaemia † 1	1/381 (0.26%)	0/377 (0.00%)
Hypochloraemia † 1	1/381 (0.26%)	0/377 (0.00%)
Hypoglycaemia † 1	1/381 (0.26%)	2/377 (0.53%)
Hypokalaemia † 1	8/381 (2.10%)	4/377 (1.06%)
Hyponatraemia † 1	4/381 (1.05%)	1/377 (0.27%)
Hypophagia † 1	2/381 (0.52%)	0/377 (0.00%)
Hypophosphataemia † 1	1/381 (0.26%)	0/377 (0.00%)
Metabolic acidosis † 1	0/381 (0.00%)	1/377 (0.27%)
Tumour lysis syndrome † 1	1/381 (0.26%)	0/377 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	2/381 (0.52%)	0/377 (0.00%)
Back pain † 1	3/381 (0.79%)	2/377 (0.53%)
Bone pain † 1	1/381 (0.26%)	1/377 (0.27%)
Bursitis † 1	1/381 (0.26%)	0/377 (0.00%)
Flank pain † 1	1/381 (0.26%)	0/377 (0.00%)
Joint swelling † 1	1/381 (0.26%)	0/377 (0.00%)
Muscular weakness † 1	0/381 (0.00%)	1/377 (0.27%)
Musculoskeletal pain † 1	1/381 (0.26%)	1/377 (0.27%)
Myalgia † 1	2/381 (0.52%)	0/377 (0.00%)
Myopathy † 1	1/381 (0.26%)	0/377 (0.00%)
Osteonecrosis of jaw † 1	1/381 (0.26%)	0/377 (0.00%)
Pain in extremity † 1	1/381 (0.26%)	1/377 (0.27%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain † 1	0/381 (0.00%)	1/377 (0.27%)
Endometrial cancer † 1	1/381 (0.26%)	0/377 (0.00%)
Prostate cancer † 1	0/381 (0.00%)	1/377 (0.27%)
Rectal cancer † 1	0/381 (0.00%)	1/377 (0.27%)
Small cell lung cancer † 1	0/381 (0.00%)	2/377 (0.53%)
Nervous system disorders
Altered state of consciousness † 1	1/381 (0.26%)	0/377 (0.00%)
Autonomic neuropathy † 1	1/381 (0.26%)	0/377 (0.00%)
Brain compression † 1	0/381 (0.00%)	1/377 (0.27%)
Brain injury † 1	0/381 (0.00%)	1/377 (0.27%)
Brain oedema † 1	1/381 (0.26%)	0/377 (0.00%)
Central nervous system haemorrhage † 1	0/381 (0.00%)	1/377 (0.27%)
Central nervous system necrosis † 1	1/381 (0.26%)	0/377 (0.00%)
Cerebral haemorrhage † 1	1/381 (0.26%)	2/377 (0.53%)
Cerebrovascular accident † 1	3/381 (0.79%)	0/377 (0.00%)
Coma † 1	1/381 (0.26%)	0/377 (0.00%)
Convulsion † 1	1/381 (0.26%)	0/377 (0.00%)
Cranial nerve paralysis † 1	0/381 (0.00%)	1/377 (0.27%)
Depressed level of consciousness † 1	1/381 (0.26%)	0/377 (0.00%)
Dizziness † 1	5/381 (1.31%)	2/377 (0.53%)
Haemorrhage intracranial † 1	1/381 (0.26%)	0/377 (0.00%)
Headache † 1	1/381 (0.26%)	0/377 (0.00%)
Hemiparesis † 1	1/381 (0.26%)	1/377 (0.27%)
Hyperreflexia † 1	0/381 (0.00%)	1/377 (0.27%)
Lacunar infarction † 1	1/381 (0.26%)	1/377 (0.27%)
Loss of consciousness † 1	5/381 (1.31%)	1/377 (0.27%)
Neuralgia † 1	1/381 (0.26%)	1/377 (0.27%)
Neuropathy peripheral † 1	3/381 (0.79%)	1/377 (0.27%)
Paraparesis † 1	1/381 (0.26%)	0/377 (0.00%)
Paraplegia † 1	0/381 (0.00%)	1/377 (0.27%)
Polyneuropathy † 1	0/381 (0.00%)	1/377 (0.27%)
Post herpetic neuralgia † 1	0/381 (0.00%)	1/377 (0.27%)
Sciatica † 1	0/381 (0.00%)	1/377 (0.27%)
Sensory loss † 1	0/381 (0.00%)	1/377 (0.27%)
Somnolence † 1	1/381 (0.26%)	0/377 (0.00%)
Speech disorder † 1	0/381 (0.00%)	1/377 (0.27%)
Syncope † 1	5/381 (1.31%)	2/377 (0.53%)
Transient ischaemic attack † 1	1/381 (0.26%)	0/377 (0.00%)
VIIth nerve paralysis † 1	0/381 (0.00%)	1/377 (0.27%)
Psychiatric disorders
Confusional state † 1	1/381 (0.26%)	1/377 (0.27%)
Delirium † 1	1/381 (0.26%)	0/377 (0.00%)
Hypomania † 1	1/381 (0.26%)	0/377 (0.00%)
Mental disorder † 1	0/381 (0.00%)	1/377 (0.27%)
Mental status changes † 1	1/381 (0.26%)	0/377 (0.00%)
Renal and urinary disorders
Anuria † 1	0/381 (0.00%)	1/377 (0.27%)
Azotaemia † 1	0/381 (0.00%)	1/377 (0.27%)
Oliguria † 1	1/381 (0.26%)	0/377 (0.00%)
Renal failure † 1	4/381 (1.05%)	4/377 (1.06%)
Renal failure acute † 1	7/381 (1.84%)	9/377 (2.39%)
Renal impairment † 1	1/381 (0.26%)	1/377 (0.27%)
Ureteric obstruction † 1	1/381 (0.26%)	0/377 (0.00%)
Reproductive system and breast disorders
Benign prostatic hyperplasia † 1	1/381 (0.26%)	0/377 (0.00%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome † 1	0/381 (0.00%)	2/377 (0.53%)
Acute respiratory failure † 1	3/381 (0.79%)	1/377 (0.27%)
Aspiration † 1	0/381 (0.00%)	1/377 (0.27%)
Asthma † 1	0/381 (0.00%)	1/377 (0.27%)
Chronic obstructive pulmonary disease † 1	0/381 (0.00%)	1/377 (0.27%)
Cough † 1	1/381 (0.26%)	0/377 (0.00%)
Dyspnoea † 1	4/381 (1.05%)	7/377 (1.86%)
Epistaxis † 1	2/381 (0.52%)	1/377 (0.27%)
Hypoventilation † 1	0/381 (0.00%)	1/377 (0.27%)
Hypoxia † 1	1/381 (0.26%)	0/377 (0.00%)
Lung disorder † 1	1/381 (0.26%)	1/377 (0.27%)
Lung infiltration † 1	1/381 (0.26%)	0/377 (0.00%)
Orthopnoea † 1	1/381 (0.26%)	1/377 (0.27%)
Pleural effusion † 1	4/381 (1.05%)	0/377 (0.00%)
Pneumonitis † 1	1/381 (0.26%)	3/377 (0.80%)
Pneumothorax † 1	1/381 (0.26%)	0/377 (0.00%)
Pulmonary embolism † 1	4/381 (1.05%)	4/377 (1.06%)
Pulmonary haemorrhage † 1	1/381 (0.26%)	0/377 (0.00%)
Pulmonary hypertension † 1	1/381 (0.26%)	0/377 (0.00%)
Pulmonary oedema † 1	1/381 (0.26%)	1/377 (0.27%)
Respiratory distress † 1	1/381 (0.26%)	0/377 (0.00%)
Respiratory failure † 1	5/381 (1.31%)	0/377 (0.00%)
Tachypnoea † 1	0/381 (0.00%)	1/377 (0.27%)
Skin and subcutaneous tissue disorders
Acute febrile neutrophilic dermatosis † 1	1/381 (0.26%)	1/377 (0.27%)
Dermatitis allergic † 1	0/381 (0.00%)	1/377 (0.27%)
Rash † 1	2/381 (0.52%)	1/377 (0.27%)
Swelling face † 1	1/381 (0.26%)	0/377 (0.00%)
Vascular disorders
Aortic stenosis † 1	1/381 (0.26%)	0/377 (0.00%)
Circulatory collapse † 1	2/381 (0.52%)	0/377 (0.00%)
Deep vein thrombosis † 1	2/381 (0.52%)	3/377 (0.80%)
Embolism † 1	1/381 (0.26%)	0/377 (0.00%)
Haematoma † 1	1/381 (0.26%)	0/377 (0.00%)
Hypotension † 1	5/381 (1.31%)	2/377 (0.53%)
Hypovolaemic shock † 1	3/381 (0.79%)	0/377 (0.00%)
Lymphoedema † 1	0/381 (0.00%)	1/377 (0.27%)
Orthostatic hypotension † 1	9/381 (2.36%)	1/377 (0.27%)
Shock haemorrhagic † 1	1/381 (0.26%)	0/377 (0.00%)
Venous thrombosis limb † 1	1/381 (0.26%)	1/377 (0.27%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	PAN+BTZ	PBO+BTZ
	Affected / at Risk (%)	Affected / at Risk (%)
Total	379/381 (99.48%)	366/377 (97.08%)
Blood and lymphatic system disorders
Anaemia † 1	154/381 (40.42%)	125/377 (33.16%)
Leukopenia † 1	61/381 (16.01%)	31/377 (8.22%)
Lymphopenia † 1	52/381 (13.65%)	35/377 (9.28%)
Neutropenia † 1	112/381 (29.40%)	40/377 (10.61%)
Thrombocytopenia † 1	238/381 (62.47%)	150/377 (39.79%)
Eye disorders
Conjunctivitis † 1	28/381 (7.35%)	31/377 (8.22%)
Gastrointestinal disorders
Abdominal distension † 1	30/381 (7.87%)	25/377 (6.63%)
Abdominal pain † 1	50/381 (13.12%)	38/377 (10.08%)
Abdominal pain upper † 1	43/381 (11.29%)	36/377 (9.55%)
Constipation † 1	101/381 (26.51%)	122/377 (32.36%)
Diarrhoea † 1	254/381 (66.67%)	155/377 (41.11%)
Dyspepsia † 1	47/381 (12.34%)	43/377 (11.41%)
Nausea † 1	137/381 (35.96%)	78/377 (20.69%)
Vomiting † 1	91/381 (23.88%)	47/377 (12.47%)
General disorders
Asthenia † 1	77/381 (20.21%)	51/377 (13.53%)
Fatigue † 1	155/381 (40.68%)	109/377 (28.91%)
Oedema peripheral † 1	108/381 (28.35%)	72/377 (19.10%)
Pyrexia † 1	90/381 (23.62%)	48/377 (12.73%)
Infections and infestations
Bronchitis † 1	20/381 (5.25%)	25/377 (6.63%)
Herpes zoster † 1	15/381 (3.94%)	36/377 (9.55%)
Nasopharyngitis † 1	49/381 (12.86%)	46/377 (12.20%)
Respiratory tract infection † 1	17/381 (4.46%)	20/377 (5.31%)
Upper respiratory tract infection † 1	65/381 (17.06%)	53/377 (14.06%)
Urinary tract infection † 1	23/381 (6.04%)	15/377 (3.98%)
Investigations
Alanine aminotransferase increased † 1	22/381 (5.77%)	19/377 (5.04%)
Blood creatinine increased † 1	37/381 (9.71%)	21/377 (5.57%)
Blood urea increased † 1	20/381 (5.25%)	10/377 (2.65%)
Platelet count decreased † 1	43/381 (11.29%)	17/377 (4.51%)
Weight decreased † 1	44/381 (11.55%)	17/377 (4.51%)
Metabolism and nutrition disorders
Decreased appetite † 1	106/381 (27.82%)	46/377 (12.20%)
Hyperglycaemia † 1	30/381 (7.87%)	25/377 (6.63%)
Hypoalbuminaemia † 1	21/381 (5.51%)	8/377 (2.12%)
Hypocalcaemia † 1	35/381 (9.19%)	32/377 (8.49%)
Hypokalaemia † 1	100/381 (26.25%)	52/377 (13.79%)
Hyponatraemia † 1	48/381 (12.60%)	18/377 (4.77%)
Hypophosphataemia † 1	42/381 (11.02%)	32/377 (8.49%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	25/381 (6.56%)	26/377 (6.90%)
Back pain † 1	45/381 (11.81%)	46/377 (12.20%)
Bone pain † 1	21/381 (5.51%)	31/377 (8.22%)
Muscle spasms † 1	23/381 (6.04%)	21/377 (5.57%)
Muscular weakness † 1	24/381 (6.30%)	20/377 (5.31%)
Myalgia † 1	24/381 (6.30%)	24/377 (6.37%)
Pain in extremity † 1	40/381 (10.50%)	54/377 (14.32%)
Nervous system disorders
Dizziness † 1	67/381 (17.59%)	61/377 (16.18%)
Dysgeusia † 1	36/381 (9.45%)	26/377 (6.90%)
Headache † 1	51/381 (13.39%)	40/377 (10.61%)
Hypoaesthesia † 1	28/381 (7.35%)	34/377 (9.02%)
Neuralgia † 1	38/381 (9.97%)	44/377 (11.67%)
Neuropathy peripheral † 1	117/381 (30.71%)	133/377 (35.28%)
Paraesthesia † 1	24/381 (6.30%)	27/377 (7.16%)
Peripheral sensory neuropathy † 1	42/381 (11.02%)	46/377 (12.20%)
Polyneuropathy † 1	28/381 (7.35%)	28/377 (7.43%)
Psychiatric disorders
Insomnia † 1	73/381 (19.16%)	61/377 (16.18%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	81/381 (21.26%)	70/377 (18.57%)
Dyspnoea † 1	53/381 (13.91%)	40/377 (10.61%)
Skin and subcutaneous tissue disorders
Rash † 1	33/381 (8.66%)	23/377 (6.10%)
Vascular disorders
Hypertension † 1	27/381 (7.09%)	23/377 (6.10%)
Hypotension † 1	49/381 (12.86%)	34/377 (9.02%)
Orthostatic hypotension † 1	22/381 (5.77%)	11/377 (2.92%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

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

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial

Results Point of Contact

• Name/Title: Study Director
• Organization: Novartis Pharmaceuticals
• Phone: 862-778-8300

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

San-Miguel JF, Einsele H, Moreau P. The Role of Panobinostat Plus Bortezomib and Dexamethasone in Treating Relapsed or Relapsed and Refractory Multiple Myeloma: A European Perspective. Adv Ther. 2016 Nov;33(11):1896-1920. doi: 10.1007/s12325-016-0413-7. Epub 2016 Sep 27.

San-Miguel JF, Hungria VT, Yoon SS, Beksac M, Dimopoulos MA, Elghandour A, Jedrzejczak WW, Gunther A, Nakorn TN, Siritanaratkul N, Schlossman RL, Hou J, Moreau P, Lonial S, Lee JH, Einsele H, Sopala M, Bengoudifa BR, Binlich F, Richardson PG. Overall survival of patients with relapsed multiple myeloma treated with panobinostat or placebo plus bortezomib and dexamethasone (the PANORAMA 1 trial): a randomised, placebo-controlled, phase 3 trial. Lancet Haematol. 2016 Nov;3(11):e506-e515. doi: 10.1016/S2352-3026(16)30147-8. Epub 2016 Oct 14.

Richardson PG, Hungria VT, Yoon SS, Beksac M, Dimopoulos MA, Elghandour A, Jedrzejczak WW, Guenther A, Nakorn TN, Siritanaratkul N, Schlossman RL, Hou J, Moreau P, Lonial S, Lee JH, Einsele H, Sopala M, Bengoudifa BR, Corrado C, Binlich F, San-Miguel JF. Panobinostat plus bortezomib and dexamethasone in previously treated multiple myeloma: outcomes by prior treatment. Blood. 2016 Feb 11;127(6):713-21. doi: 10.1182/blood-2015-09-665018. Epub 2015 Dec 2. Erratum In: Blood. 2016 Jun 30;127(26):3460.

San-Miguel JF, Hungria VT, Yoon SS, Beksac M, Dimopoulos MA, Elghandour A, Jedrzejczak WW, Gunther A, Nakorn TN, Siritanaratkul N, Corradini P, Chuncharunee S, Lee JJ, Schlossman RL, Shelekhova T, Yong K, Tan D, Numbenjapon T, Cavenagh JD, Hou J, LeBlanc R, Nahi H, Qiu L, Salwender H, Pulini S, Moreau P, Warzocha K, White D, Blade J, Chen W, de la Rubia J, Gimsing P, Lonial S, Kaufman JL, Ocio EM, Veskovski L, Sohn SK, Wang MC, Lee JH, Einsele H, Sopala M, Corrado C, Bengoudifa BR, Binlich F, Richardson PG. Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1195-206. doi: 10.1016/S1470-2045(14)70440-1. Epub 2014 Sep 18. Erratum In: Lancet Oncol. 2015 Jan;16(1):e6.

• Responsible Party: Novartis ( Novartis Pharmaceuticals )
• ClinicalTrials.gov Identifier: NCT01023308
• Other Study ID Numbers: CLBH589D2308; 2009-015507-52 ( EudraCT Number )
• First Submitted: November 30, 2009
• First Posted: December 2, 2009
• Results First Submitted: March 23, 2015
• Results First Posted: October 23, 2015
• Last Update Posted: March 17, 2020