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

NCT ID: NCT01023308

Last Updated: 2020-03-17

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

767 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-12-21

Study Completion Date

2015-07-30

Brief Summary

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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.

Detailed Description

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Conditions

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Multiple Myeloma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Panobinostat + Bortezomib + Dexamethasone

Group Type EXPERIMENTAL

Panobinostat

Intervention Type DRUG

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

Bortezomib

Intervention Type DRUG

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

Dexamethasone

Intervention Type DRUG

Dexamethasone was adminstered on day of Bortezomib and the day after Bortezomib administration

Placebo + Bortezomib + Dexamethasone

Group Type PLACEBO_COMPARATOR

Bortezomib

Intervention Type DRUG

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

Dexamethasone

Intervention Type DRUG

Dexamethasone was adminstered on day of Bortezomib and the day after Bortezomib administration

Placebo

Intervention Type DRUG

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

Interventions

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Panobinostat

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

Intervention Type DRUG

Bortezomib

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

Intervention Type DRUG

Dexamethasone

Dexamethasone was adminstered on day of Bortezomib and the day after Bortezomib administration

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Other Intervention Names

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LBH589 (Velcade®)

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Novartis Investigative Site

Phoenix, Arizona, United States

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Anaheim, California, United States

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Concord, California, United States

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Los Angeles, California, United States

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San Diego, California, United States

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Stanford, California, United States

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Boca Raton, Florida, United States

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Lake Worth, Florida, United States

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Miami Shores, Florida, United States

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Athens, Georgia, United States

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Atlanta, Georgia, United States

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Marietta, Georgia, United States

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Marywood, Illinois, United States

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Quincy, Illinois, United States

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New Orleans, Louisiana, United States

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Baltimore, Maryland, United States

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Rockville, Maryland, United States

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Boston, Massachusetts, United States

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Southfield, Michigan, United States

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Edina, Minnesota, United States

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Minneapolis, Minnesota, United States

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Columbia, Missouri, United States

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East Orange, New Jersey, United States

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Mount Kisco, New York, United States

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Durham, North Carolina, United States

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Bismarck, North Dakota, United States

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Dayton, Ohio, United States

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Middletown, Ohio, United States

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Pittsburgh, Pennsylvania, United States

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East Providence, Rhode Island, United States

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Nashville, Tennessee, United States

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Nashville, Tennessee, United States

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Amarillo, Texas, United States

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Houston, Texas, United States

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Kennewick, Washington, United States

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Seattle, Washington, United States

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Walla Walla, Washington, United States

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Morgantown, West Virginia, United States

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La Plata, Buenos Aires, Argentina

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Buenos Aires, , Argentina

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Córdoba, , Argentina

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St Leonards, New South Wales, Australia

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Herston, Queensland, Australia

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Woolloongabba, Queensland, Australia

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Franston, Victoria, Australia

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Nedlands, Western Australia, Australia

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Perth, Western Australia, Australia

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Linz, , Austria

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Vienna, , Austria

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Jette, Brussels Capital, Belgium

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Brussels, , Belgium

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Hasselt, , Belgium

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Brasília, Federal District, Brazil

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Rio de Janeiro, Rio de Janeiro, Brazil

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Rio de Janeiro, Rio de Janeiro, Brazil

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São Paulo, São Paulo, Brazil

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Halifax, Nova Scotia, Canada

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Hamilton, Ontario, Canada

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Toronto, Ontario, Canada

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Greenfield Park, Quebec, Canada

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Montreal, Quebec, Canada

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Beijing, Beijing Municipality, China

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Nanning, Guangxi, China

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Nanjing, Jiangsu, China

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Brno Bohunice, Czech Republic, Czechia

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Olomouc, CZE, Czechia

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Aalborg, , Denmark

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Aarhus, , Denmark

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Odense, , Denmark

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Vejle, , Denmark

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Alexandria, , Egypt

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Giza, , Egypt

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HUS Helsinki, , Finland

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Turku, , Finland

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Blois, , France

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Dijon, , France

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Lille, , France

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Limoges, , France

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Nantes, , France

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Vandœuvre-lès-Nancy, , France

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Aachen, , Germany

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Bad Saarow, , Germany

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Ulm, , Germany

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Jerusalem, , Israel

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Kfar Saba, , Israel

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Petah Tikva, , Israel

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Ramat Gan, , Israel

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San Giovanni Rotondo, FG, Italy

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Lecce, LE, Italy

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Milan, MI, Italy

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Pescara, PE, Italy

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Pisa, PI, Italy

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Pavia, PV, Italy

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Reggio Calabria, RC, Italy

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Roma, RM, Italy

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Roma, RM, Italy

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Pagani, SA, Italy

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Verona, VR, Italy

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Napoli, , Italy

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Nagoya, Aichi-ken, Japan

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Nagoya, Aichi-ken, Japan

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Matsuyama, Ehime, Japan

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Fukuoka, Fukuoka, Japan

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Ōgaki, Gifu, Japan

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Shibukawa, Gunma, Japan

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Kure, Hiroshima, Japan

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Higashiibaraki-gun, Ibaraki, Japan

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Okayama, Okayama-ken, Japan

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Suita, Osaka, Japan

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Shibuya City, Tokyo, Japan

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Hiroshima, , Japan

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Niigata, , Japan

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Osaka, , Japan

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Beirut, , Lebanon

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San Luis Potosí City, , Mexico

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Rotterdam, , Netherlands

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Rotterdam, , Netherlands

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Utrecht, , Netherlands

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Fredrikstad, , Norway

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Skien, , Norway

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Trondheim, , Norway

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Saint Petersburg, , Russia

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Saratov, , Russia

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Singapore, , Singapore

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Parktown, , South Africa

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Pretoria, , South Africa

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Suwon, Gyeonggi-do, South Korea

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Jeollanam-do, Jeollanam-do, South Korea

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Seoul, Seocho Gu, South Korea

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Busan, , South Korea

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Busan, , South Korea

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Incheon, , South Korea

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Seoul, , South Korea

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Taegu, , South Korea

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Córdoba, Andalusia, Spain

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Seville, Andalusia, Spain

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Donostia / San Sebastian, Basque Country, Spain

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Salamanca, Castille and León, Spain

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Barcelona, Catalonia, Spain

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Santiago de Compostela, Galicia, Spain

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Pamplona, Navarre, Spain

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San Cristóbal de La Laguna, Santa Cruz De Tenerife, Spain

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Valencia, Valencia, Spain

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Barcelona, , Spain

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Gothenburg, , Sweden

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Linköping, , Sweden

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Luleå, , Sweden

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Stockholm, , Sweden

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Uppsala, , Sweden

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Kaohsiung City, , Taiwan

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Taichung, , Taiwan

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Taipei, , Taiwan

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Bangkok, , Thailand

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Istanbul, TUR, Turkey (Türkiye)

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Adana, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Aberdeen, Scotland, United Kingdom

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Glasgow, Scotland, United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Wolverhampton, , United Kingdom

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Countries

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

References

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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.

Reference Type DERIVED
PMID: 27751707 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27677481 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26631116 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25242045 (View on PubMed)

Related Links

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Other Identifiers

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2009-015507-52

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLBH589D2308

Identifier Type: -

Identifier Source: org_study_id

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