Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma

Multiple Myeloma Clinical Trial

— PANORAMA-1  

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01023308
• Other study ID #: CLBH589D2308
• Secondary ID: 2009-015507-52
• Status: Completed
• Phase: Phase 3
• Start date: December 21, 2009
• Est. completion date: July 30, 2015

Study information

• Verified date: March 2020
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 protease 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 whose disease has recurred or progressed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 767
• Est. completion date: July 30, 2015
• Est. primary completion date: July 30, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patient has a previous diagnosis of multiple myeloma.

2. Patient requires retreatment for multiple myeloma

3. Patient has measurable M component in serum or urine at study screening

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Panobinostat
Panobinostat was administered 3x week ( 2 weeks on 1 week off)
• Bortezomib
Bortezomib was administered 2 x week ( 2weeks on 1 week off)
• Dexamethasone
Dexamethasone was adminstered on day of Bortezomib and the day after Bortezomib administration
• Placebo
Placebo was administered 3x week ( 2 weeks on 1 week off)

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	La Plata	Buenos Aires
Australia	Novartis Investigative Site	Franston	Victoria
Australia	Novartis Investigative Site	Herston	Queensland
Australia	Novartis Investigative Site	Nedlands	Western Australia
Australia	Novartis Investigative Site	Perth	Western Australia
Australia	Novartis Investigative Site	St Leonards	New South Wales
Australia	Novartis Investigative Site	Woolloongabba	Queensland
Austria	Novartis Investigative Site	Linz
Austria	Novartis Investigative Site	Wien
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Hasselt
Belgium	Novartis Investigative Site	Jette	Brussel
Brazil	Novartis Investigative Site	Barretos	SP
Brazil	Novartis Investigative Site	Brasilia	DF
Brazil	Novartis Investigative Site	Campinas	SP
Brazil	Novartis Investigative Site	Rio de Janeiro	RJ
Brazil	Novartis Investigative Site	Rio de Janeiro	RJ
Brazil	Novartis Investigative Site	Rio de Janeiro	RJ
Brazil	Novartis Investigative Site	Sao Paulo	SP
Brazil	Novartis Investigative Site	São Paulo	SP
Canada	Novartis Investigative Site	Greenfield Park	Quebec
Canada	Novartis Investigative Site	Halifax	Nova Scotia
Canada	Novartis Investigative Site	Hamilton	Ontario
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Toronto	Ontario
China	Novartis Investigative Site	Beijing	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Chengdu	Sichuan
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Nanjing	Jiangsu
China	Novartis Investigative Site	Nanning	Guangxi
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Suzhou	Jiangsu
China	Novartis Investigative Site	Tianjin	Tianjin
Czechia	Novartis Investigative Site	Brno Bohunice	Czech Republic
Czechia	Novartis Investigative Site	Olomouc	CZE
Czechia	Novartis Investigative Site	Prague 2	Czech Republic
Denmark	Novartis Investigative Site	Ålborg
Denmark	Novartis Investigative Site	Århus
Denmark	Novartis Investigative Site	Copenhagen
Denmark	Novartis Investigative Site	Odense
Denmark	Novartis Investigative Site	Vejle
Egypt	Novartis Investigative Site	Alexandria
Egypt	Novartis Investigative Site	Giza
Finland	Novartis Investigative Site	HUS Helsinki
Finland	Novartis Investigative Site	Turku
France	Novartis Investigative Site	Blois Cedex
France	Novartis Investigative Site	Dijon
France	Novartis Investigative Site	Lille Cedex
France	Novartis Investigative Site	Limoges cedex
France	Novartis Investigative Site	Nantes
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Pierre Benite
France	Novartis Investigative Site	Strasbourg cedex
France	Novartis Investigative Site	Vandoeuvre Les Nancy
Germany	Novartis Investigative Site	Aachen
Germany	Novartis Investigative Site	Bad Saarow
Germany	Novartis Investigative Site	Bamberg
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bremen
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Duisburg
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Jena
Germany	Novartis Investigative Site	Kiel
Germany	Novartis Investigative Site	Magdeburg
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Rostock
Germany	Novartis Investigative Site	Ulm
Germany	Novartis Investigative Site	Wuerzburg
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Thessaloniki	GR
Hong Kong	Novartis Investigative Site	Hong Kong
Hong Kong	Novartis Investigative Site	Hong Kong SAR
Hong Kong	Novartis Investigative Site	New Territories
Israel	Novartis Investigative Site	Jerusalem
Israel	Novartis Investigative Site	Kfar Saba
Israel	Novartis Investigative Site	Petach Tikva
Israel	Novartis Investigative Site	Ramat Gan
Italy	Novartis Investigative Site	Lecce	LE
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Pagani	SA
Italy	Novartis Investigative Site	Pavia	PV
Italy	Novartis Investigative Site	Pescara	PE
Italy	Novartis Investigative Site	Pisa	PI
Italy	Novartis Investigative Site	Reggio Calabria	RC
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	San Giovanni Rotondo	FG
Italy	Novartis Investigative Site	Verona	VR
Japan	Novartis Investigative Site	Fukuoka city	Fukuoka
Japan	Novartis Investigative Site	Higashiibaraki-gun	Ibaraki
Japan	Novartis Investigative Site	Hiroshima
Japan	Novartis Investigative Site	Kure-city	Hiroshima
Japan	Novartis Investigative Site	Matsuyama-city	Ehime
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Nagoya-city	Aichi
Japan	Novartis Investigative Site	Niigata
Japan	Novartis Investigative Site	Ogaki-city	Gifu
Japan	Novartis Investigative Site	Okayama city	Okayama
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Shibukawa	Gunma
Japan	Novartis Investigative Site	Shibuya	Tokyo
Japan	Novartis Investigative Site	Suita city	Osaka
Korea, Republic of	Novartis Investigative Site	Busan
Korea, Republic of	Novartis Investigative Site	Busan
Korea, Republic of	Novartis Investigative Site	Incheon
Korea, Republic of	Novartis Investigative Site	Jeollanam-do
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul	Seocho Gu
Korea, Republic of	Novartis Investigative Site	Suwon si	Gyeonggi Do
Korea, Republic of	Novartis Investigative Site	Taegu
Lebanon	Novartis Investigative Site	Beirut
Mexico	Novartis Investigative Site	San Luis Potosí
Netherlands	Novartis Investigative Site	Rotterdam
Netherlands	Novartis Investigative Site	Rotterdam
Netherlands	Novartis Investigative Site	Utrecht
Norway	Novartis Investigative Site	Bergen
Norway	Novartis Investigative Site	Fredrikstad
Norway	Novartis Investigative Site	Kristiansand
Norway	Novartis Investigative Site	Oslo
Norway	Novartis Investigative Site	Skien
Norway	Novartis Investigative Site	Trondheim
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Warszawa
Russian Federation	Novartis Investigative Site	Saratov
Russian Federation	Novartis Investigative Site	St Petersburg
Singapore	Novartis Investigative Site	Singapore
South Africa	Novartis Investigative Site	Parktown
South Africa	Novartis Investigative Site	Pretoria
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Cordoba	Andalucia
Spain	Novartis Investigative Site	La Laguna	Santa Cruz De Tenerife
Spain	Novartis Investigative Site	Pamplona	Navarra
Spain	Novartis Investigative Site	Salamanca	Castilla Y Leon
Spain	Novartis Investigative Site	San Sebastian	Pais Vasco
Spain	Novartis Investigative Site	Santiago de Compostela	Galicia
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Sweden	Novartis Investigative Site	Göteborg
Sweden	Novartis Investigative Site	Linköping
Sweden	Novartis Investigative Site	Luleå
Sweden	Novartis Investigative Site	Stockholm
Sweden	Novartis Investigative Site	Uppsala
Taiwan	Novartis Investigative Site	Kaohsiung City
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taoyuan
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Turkey	Novartis Investigative Site	Adana
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Istanbul	TUR
United Kingdom	Novartis Investigative Site	Aberdeen	Scotland
United Kingdom	Novartis Investigative Site	Glasgow	Scotland
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Manchester
United Kingdom	Novartis Investigative Site	Wolverhampton
United States	Novartis Investigative Site	Amarillo	Texas
United States	Novartis Investigative Site	Anaheim	California
United States	Novartis Investigative Site	Athens	Georgia
United States	Novartis Investigative Site	Atlanta	Georgia
United States	Novartis Investigative Site	Baltimore	Maryland
United States	Novartis Investigative Site	Bismarck	North Dakota
United States	Novartis Investigative Site	Boca Raton	Florida
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Columbia	Missouri
United States	Novartis Investigative Site	Concord	California
United States	Novartis Investigative Site	Dayton	Ohio
United States	Novartis Investigative Site	Durham	North Carolina
United States	Novartis Investigative Site	East Orange	New Jersey
United States	Novartis Investigative Site	East Providence	Rhode Island
United States	Novartis Investigative Site	Edina	Minnesota
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Kennewick	Washington
United States	Novartis Investigative Site	Lake Worth	Florida
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Marietta	Georgia
United States	Novartis Investigative Site	Marywood	Illinois
United States	Novartis Investigative Site	Miami Shores	Florida
United States	Novartis Investigative Site	Middletown	Ohio
United States	Novartis Investigative Site	Minneapolis	Minnesota
United States	Novartis Investigative Site	Morgantown	West Virginia
United States	Novartis Investigative Site	Mount Kisco	New York
United States	Novartis Investigative Site	Nashville	Tennessee
United States	Novartis Investigative Site	Nashville	Tennessee
United States	Novartis Investigative Site	New Orleans	Louisiana
United States	Novartis Investigative Site	Phoenix	Arizona
United States	Novartis Investigative Site	Pittsburgh	Pennsylvania
United States	Novartis Investigative Site	Quincy	Illinois
United States	Novartis Investigative Site	Rockville	Maryland
United States	Novartis Investigative Site	San Diego	California
United States	Novartis Investigative Site	Seattle	Washington
United States	Novartis Investigative Site	Southfield	Michigan
United States	Novartis Investigative Site	Stanford	California
United States	Novartis Investigative Site	Walla Walla	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  China,  Czechia,  Denmark,  Egypt,  Finland,  France,  Germany,  Greece,  Hong Kong,  Israel,  Italy,  Japan,  Korea, Republic of,  Lebanon,  Mexico,  Netherlands,  Norway,  Poland,  Russian Federation,  Singapore,  South Africa,  Spain,  Sweden,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		45 months
Primary	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.		45 months
Secondary	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	45 months
Secondary	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	45 months
Secondary	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	45 months
Secondary	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.		45 months
Secondary	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.		45 months
Secondary	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.		45 months
Secondary	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.	12, 24 and 48 weeks
Secondary	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.	12, 24 and 48 weeks
Secondary	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.	12, 24 and 48 weeks

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