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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01023308




Registration number
NCT01023308
Ethics application status
Date submitted
30/11/2009
Date registered
2/12/2009
Date last updated
29/12/2016

Titles & IDs
Public title
Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma
Scientific title
A Multicenter, Randomized, Double Blind, Placebo Controlled Phase III Study of Panobinostat in Combination With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma
Secondary ID [1] 0 0
2009-015507-52
Secondary ID [2] 0 0
CLBH589D2308
Universal Trial Number (UTN)
Trial acronym
PANORAMA-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Panobinostat
Treatment: Drugs - Bortezomib
Treatment: Drugs - Placebo

Experimental: Panobinostat + Bortezomib -

Placebo Comparator: Placebo + Bortezomib -


Treatment: Drugs: Panobinostat
Panobinostat was administered 3x week ( 2 weeks on 1 week off)

Treatment: Drugs: Bortezomib
Bortezomib was administered 2 x week ( 2weeks on 1 week off)

Treatment: Drugs: Placebo
Placebo was administered 3x week ( 2 weeks on 1 week off)

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
45 months
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
45 months
Secondary outcome [1] 0 0
Overall Survival in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone - Number of OS events
Timepoint [1] 0 0
45 months
Secondary outcome [2] 0 0
Overall Survival in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone - survival time in months
Timepoint [2] 0 0
45 months
Secondary outcome [3] 0 0
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. - Best overall response based on mEBMT criteria per investigator assessment
Timepoint [3] 0 0
45 months
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
45 months
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
45 months
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
45 months
Secondary outcome [7] 0 0
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC) QLQ-MY20-Change From Baseline by Treatment Group - 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.
Timepoint [7] 0 0
12, 24 and 48 weeks
Secondary outcome [8] 0 0
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group - 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.
Timepoint [8] 0 0
12, 24 and 48 weeks
Secondary outcome [9] 0 0
Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System : FACT/GOG-NTX-Change From Baseline by Treatment Group - 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.
Timepoint [9] 0 0
12, 24 and 48 weeks

Eligibility
Key inclusion criteria
1. Patient has a previous diagnosis of multiple myeloma.

2. Patient with 1-3 prior lines of therapy who require retreatment for multiple myeloma

3. Patient has measurable disease (M-protein) in serum or urine at study screening
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patient who has progressed under all prior lines of anti MM therapy

2. Patient who has been treated by bortezomib before, and did not reach at least a minor
response under this therapy, or progressed under it or within 60 days of last dose

3. Patient has shown intolerance to bortezomib or to dexamethasone or components of these
drugs or has any contraindication to one or the other drug , following locally
applicable prescribing information

4. Patient received prior treatment with DAC inhibitors including panobinostat

5. Patient has impaired cardiac function, or a prolonged QTc interval at screening ECG

6. Patient taking medications with relative risk of prolonging the QT interval or
inducing Torsade de pointes

7. Female patient who is pregnant or breast feeding or with childbearing potential and
not willing to use a double method of contraception up to 3 months after the end of
study treatment. Male patient who is not willing to use a barrier method of
contraception up to 3 months after the end of study treatment.

Other protocol-defined inclusion/exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
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Novartis Investigative Site - St. Leonards
Recruitment hospital [2] 0 0
Novartis Investigative Site - Herston
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Novartis Investigative Site - Woolloongabba
Recruitment hospital [4] 0 0
Novartis Investigative Site - Franston
Recruitment hospital [5] 0 0
Novartis Investigative Site - Nedlands
Recruitment hospital [6] 0 0
Novartis Investigative Site - Perth
Recruitment postcode(s) [1] 0 0
2065 - St. Leonards
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 0 0
3199 - Franston
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6009 - Nedlands
Recruitment postcode(s) [6] 0 0
6000 - Perth
Recruitment outside Australia
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Barcelona
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Göteborg
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Linköping
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Luleå
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Manchester
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Wolverhampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Panobinostat (LBH589) is a highly potent pan-deacetylase inhibitor (pan-DACi), inclusive of
HDAC6, which disrupts aggresome function, promotes accumulation of cytotoxic misfolded
protein aggregates and triggers myeloma cell death. Combination of pan-DAC and proteasome
inhibition by co-treatment with panobinostat (PAN) and bortezomib (BTZ) has demonstrated
synergistic cytotoxicity in vitro and in vivo in pre-clinical experiments. Furthermore,
clinical experience in advanced multiple myeloma (MM) patients treated by oral panobinostat
and i.v bortezomib ± dexamethasone showed very encouraging results for efficacy and
manageable toxicity profile.

Given the medical need for improved treatment strategies for patients with previously treated
and relapsed MM, the purpose of this prospective, multinational, randomized, double-blind,
placebo-controlled, parallel group Phase III study is to compare the results in
progression-free survival of 2 combination therapies, panobinostat with bortezomib and
dexamethasone or placebo with bortezomib and dexamethasone, in patients with previously
treated MM who recurred after 1-3 prior lines of therapy
Trial website
https://clinicaltrials.gov/show/NCT01023308
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications