Multiple MyelomaPhase 3PANORAMA-1NCT01023308
Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma
A Phase 3 study testing Panobinostat, Bortezomib and Dexamethasone in people with Multiple Myeloma, run by Novartis Pharmaceuticals at 210 sites in 34 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Panobinostat, Bortezomib and Dexamethasone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 767 participants
- Where
- 210 sitesin 34 countries
- Study dates
- 21 Dec 2009to 30 Jul 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient has a previous diagnosis of multiple myeloma.
- Patient requires retreatment for multiple myeloma
- Patient has measurable M component in serum or urine at study screening
Who cannot join
- Patient who has progressed under all prior lines of anti MM therapy
- 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
- 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
- Patient received prior treatment with DAC inhibitors including panobinostat
- Patient has impaired cardiac function, or a prolonged QTc interval at screening ECG
- Patient taking medications with relative risk of prolonging the QT interval or inducing Torsade de pointes
- 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.
Trial locations and contacts
210 sites in 34 countries.
210 sites in 34 countries
United States38 sites
Novartis Investigative Site
Amarillo, Texas, 79106
Novartis Investigative Site
Anaheim, California, 92801
Novartis Investigative Site
Athens, Georgia, 30607
Novartis Investigative Site
Atlanta, Georgia, 30322
Novartis Investigative Site
Baltimore, Maryland, 21229
Novartis Investigative Site
Bismarck, North Dakota, 58501
Novartis Investigative Site
Boca Raton, Florida, 33486
Novartis Investigative Site
Boston, Massachusetts, 02215
Novartis Investigative Site
Columbia, Missouri, 65201
Novartis Investigative Site
Concord, California, 94520
Novartis Investigative Site
Dayton, Ohio, 45429
Novartis Investigative Site
Durham, North Carolina, 27710
Novartis Investigative Site
East Orange, New Jersey, 07018-1095
Novartis Investigative Site
East Providence, Rhode Island, 02915
Novartis Investigative Site
Edina, Minnesota, 55435
Novartis Investigative Site
Houston, Texas, 77030
Novartis Investigative Site
Kennewick, Washington, 99336
Novartis Investigative Site
Lake Worth, Florida, 33467
Novartis Investigative Site
Los Angeles, California, 90027
Novartis Investigative Site
Marietta, Georgia, 30060
Novartis Investigative Site
Marywood, Illinois, 60153
Novartis Investigative Site
Miami Shores, Florida, 33138
Novartis Investigative Site
Middletown, Ohio, 45042
Novartis Investigative Site
Minneapolis, Minnesota, 55404
Novartis Investigative Site
Morgantown, West Virginia, 26506
Novartis Investigative Site
Mount Kisco, New York, 10549
Novartis Investigative Site
Nashville, Tennessee, 37203
Novartis Investigative Site
Nashville, Tennessee, 37232
Novartis Investigative Site
New Orleans, Louisiana, 70115
Novartis Investigative Site
Phoenix, Arizona
Novartis Investigative Site
Pittsburgh, Pennsylvania, 15224
Novartis Investigative Site
Quincy, Illinois, 62301
Novartis Investigative Site
Rockville, Maryland, 20850
Novartis Investigative Site
San Diego, California, 92120
Novartis Investigative Site
Seattle, Washington, 98104
Novartis Investigative Site
Southfield, Michigan
Novartis Investigative Site
Stanford, California, 94304
Novartis Investigative Site
Walla Walla, Washington, 33962
Germany17 sites
Novartis Investigative Site
Aachen, 52074
Novartis Investigative Site
Bad Saarow, 15526
Novartis Investigative Site
Bamberg, 96049
Novartis Investigative Site
Berlin, 13353
Novartis Investigative Site
Bremen, 28177
Novartis Investigative Site
Dresden, 01307
Novartis Investigative Site
Duisburg, 47166
Novartis Investigative Site
Erlangen, 91054
Novartis Investigative Site
Frankfurt, 60590
Novartis Investigative Site
Hamburg, 22763
Novartis Investigative Site
Jena, 07740
Novartis Investigative Site
Kiel, 24105
Novartis Investigative Site
Magdeburg, 39120
Novartis Investigative Site
München, 81737
Novartis Investigative Site
Rostock, 18057
Novartis Investigative Site
Ulm, 89081
Novartis Investigative Site
Würzburg, 97080
Japan14 sites
Novartis Investigative Site
Fukuoka, Fukuoka, 812-8582
Novartis Investigative Site
Higashiibaraki-gun, Ibaraki, 311-3193
Novartis Investigative Site
Hiroshima, 734-8551
Novartis Investigative Site
Kure, Hiroshima, 737-0023
Novartis Investigative Site
Matsuyama, Ehime, 790-8524
Novartis Investigative Site
Nagoya, Aichi-ken, 460-0001
Novartis Investigative Site
Nagoya, Aichi-ken, 467-8602
Novartis Investigative Site
Niigata, 951-8566
Novartis Investigative Site
Ōgaki, Gifu, 503-8502
Novartis Investigative Site
Okayama, Okayama-ken, 701-1192
Novartis Investigative Site
Osaka, 545-8586
Novartis Investigative Site
Shibukawa, Gunma, 377-8511
Novartis Investigative Site
Shibuya City, Tokyo, 150-8935
Novartis Investigative Site
Suita, Osaka, 565 0871
Italy12 sites
Novartis Investigative Site
Lecce, LE, 73100
Novartis Investigative Site
Milan, MI, 20133
Novartis Investigative Site
Naples, 80131
Novartis Investigative Site
Pagani, SA, 84016
Novartis Investigative Site
Pavia, PV, 27100
Novartis Investigative Site
Pescara, PE, 65124
Novartis Investigative Site
Pisa, PI, 56126
Novartis Investigative Site
Reggio Calabria, RC, 89124
Novartis Investigative Site
Roma, RM, 00144
Novartis Investigative Site
Roma, RM, 00161
Novartis Investigative Site
San Giovanni Rotondo, FG, 71013
Novartis Investigative Site
Verona, VR, 37134
China11 sites
Novartis Investigative Site
Beijing, Beijing Municipality, 100730
Novartis Investigative Site
Beijing, 100020
Novartis Investigative Site
Beijing, 100044
Novartis Investigative Site
Chengdu, Sichuan, 610041
Novartis Investigative Site
Hangzhou, Zhejiang, 310003
Novartis Investigative Site
Nanjing, Jiangsu, 210029
Novartis Investigative Site
Nanning, Guangxi, 530021
Novartis Investigative Site
Shanghai, 200003
Novartis Investigative Site
Shanghai, 200025
Novartis Investigative Site
Suzhou, Jiangsu, 215006
Novartis Investigative Site
Tianjin, Tianjin Municipality, 300020
South Korea10 sites
Novartis Investigative Site
Busan, 49201
Novartis Investigative Site
Busan, 602739
Novartis Investigative Site
Incheon, 405 760
Novartis Investigative Site
Jeollanam-do, Jeollanam-do, 519763
Novartis Investigative Site
Seoul, Seocho Gu, 06591
Novartis Investigative Site
Seoul, 03080
Novartis Investigative Site
Seoul, 03722
Novartis Investigative Site
Seoul, 06351
Novartis Investigative Site
Suwon, Gyeonggi-do, 16499
Novartis Investigative Site
Taegu, 41944
Spain10 sites
Novartis Investigative Site
Barcelona, Catalonia, 08036
Novartis Investigative Site
Barcelona, 08041
Novartis Investigative Site
Córdoba, Andalusia, 14004
Novartis Investigative Site
Donostia / San Sebastian, Basque Country, 20080
Novartis Investigative Site
Pamplona, Navarre, 31008
Novartis Investigative Site
Salamanca, Castille and León, 37007
Novartis Investigative Site
San Cristóbal de La Laguna, Santa Cruz De Tenerife, 38320
Novartis Investigative Site
Santiago de Compostela, Galicia, 15706
Novartis Investigative Site
Seville, Andalusia, 41013
Novartis Investigative Site
Valencia, Valencia, 46026
France9 sites
Novartis Investigative Site
Blois, 41016
Novartis Investigative Site
Dijon, 21034
Novartis Investigative Site
Lille, 59037
Novartis Investigative Site
Limoges, 87042
Novartis Investigative Site
Nantes, 44035
Novartis Investigative Site
Paris, 75231
Novartis Investigative Site
Pierre-Bénite, 69310
Novartis Investigative Site
Strasbourg, 67085
Novartis Investigative Site
Vandœuvre-lès-Nancy, 54511
Brazil8 sites
Novartis Investigative Site
Barretos, São Paulo, 14784 400
Novartis Investigative Site
Brasília, Federal District, 70710-904
Novartis Investigative Site
Campinas, São Paulo, 13083-970
Novartis Investigative Site
Rio de Janeiro, Rio de Janeiro, 20.211-030
Novartis Investigative Site
Rio de Janeiro, Rio de Janeiro, 20551-030
Novartis Investigative Site
Rio de Janeiro, Rio de Janeiro, 22640-102
Novartis Investigative Site
São Paulo, São Paulo, 01224-000
Novartis Investigative Site
São Paulo, São Paulo, 05403 000
United Kingdom8 sites
Novartis Investigative Site
Aberdeen, Scotland, AB25 2ZN
Novartis Investigative Site
Glasgow, Scotland, G12 0YN
Novartis Investigative Site
London, EC1A 7BE
Novartis Investigative Site
London, SE5 9RS
Novartis Investigative Site
London, W12 0HS
Novartis Investigative Site
London, WC1E 6HX
Novartis Investigative Site
Manchester, M20 4BX
Novartis Investigative Site
Wolverhampton, WV10 0QP
Australia6 sites
Novartis Investigative Site
Franston, Victoria, 3199
Novartis Investigative Site
Herston, Queensland, 4029
Novartis Investigative Site
Nedlands, Western Australia, 6009
Novartis Investigative Site
Perth, Western Australia, 6000
Novartis Investigative Site
St Leonards, New South Wales, 2065
Novartis Investigative Site
Woolloongabba, Queensland, 4102
Norway6 sites
Novartis Investigative Site
Bergen, NO-5021
Novartis Investigative Site
Fredrikstad, NO-1603
Novartis Investigative Site
Kristiansand, NO-4605
Novartis Investigative Site
Oslo, 0407
Novartis Investigative Site
Skien, NO-3710
Novartis Investigative Site
Trondheim, 7006
Canada5 sites
Novartis Investigative Site
Greenfield Park, Quebec, J4V 2H1
Novartis Investigative Site
Halifax, Nova Scotia, B3H 1V7
Novartis Investigative Site
Hamilton, Ontario, L8V 5C2
Novartis Investigative Site
Montreal, Quebec, H1T 2M4
Novartis Investigative Site
Toronto, Ontario, M5G 2M9
Denmark5 sites
Novartis Investigative Site
Aalborg, DK-9100
Novartis Investigative Site
Aarhus, DK-8000
Novartis Investigative Site
Copenhagen, DK-2100
Novartis Investigative Site
Odense, DK 5000
Novartis Investigative Site
Vejle, DK-7100
Sweden5 sites
Novartis Investigative Site
Gothenburg, SE-413 45
Novartis Investigative Site
Linköping, SE-581 85
Novartis Investigative Site
Luleå, SE-971 80
Novartis Investigative Site
Stockholm, SE-118 83
Novartis Investigative Site
Uppsala, SE-751 85
Israel4 sites
Novartis Investigative Site
Jerusalem, 91120
Novartis Investigative Site
Kfar Saba, 4428164
Novartis Investigative Site
Petah Tikva, 49100
Novartis Investigative Site
Ramat Gan, 5265601
Taiwan4 sites
Novartis Investigative Site
Kaohsiung City, 83301
Novartis Investigative Site
Taichung, 40447
Novartis Investigative Site
Taipei, 10048
Novartis Investigative Site
Taoyuan, 333
Argentina3 sites
Novartis Investigative Site
Buenos Aires, C1114AAN
Novartis Investigative Site
Córdoba, X5000JHQ
Novartis Investigative Site
La Plata, Buenos Aires, B1900AWT
Belgium3 sites
Novartis Investigative Site
Brussels, 1200
Novartis Investigative Site
Hasselt, 3500
Novartis Investigative Site
Jette, Brussels Capital, 1090
Czechia3 sites
Novartis Investigative Site
Brno-Bohunice, Czech Republic, 625 00
Novartis Investigative Site
Olomouc, CZE, 775 20
Novartis Investigative Site
Prague, Czech Republic, 128 08
Hong Kong3 sites
Novartis Investigative Site
Hong Kong
Novartis Investigative Site
Hong Kong SAR
Novartis Investigative Site
New Territories, Hong Kong
Netherlands3 sites
Novartis Investigative Site
Rotterdam, 3015 CE
Novartis Investigative Site
Rotterdam
Novartis Investigative Site
Utrecht, 3584 CX
Thailand3 sites
Novartis Investigative Site
Bangkok, 10330
Novartis Investigative Site
Bangkok, 10400
Novartis Investigative Site
Bangkok, 10700
Turkey (Türkiye)3 sites
Novartis Investigative Site
Adana, 01330
Novartis Investigative Site
Ankara, 06100
Novartis Investigative Site
Istanbul, TUR, 34098
Austria2 sites
Novartis Investigative Site
Linz, A-4010
Novartis Investigative Site
Vienna, A-1090
Egypt2 sites
Novartis Investigative Site
Alexandria, 21131
Novartis Investigative Site
Giza, 11451
Finland2 sites
Novartis Investigative Site
HUS Helsinki, FIN-00029
Novartis Investigative Site
Turku, FIN-20521
Greece2 sites
Novartis Investigative Site
Athens, 115 28
Novartis Investigative Site
Thessaloniki, GR, 570 10
Poland2 sites
Novartis Investigative Site
Warsaw, 02 776
Novartis Investigative Site
Warsaw, 02-097
Russia2 sites
Novartis Investigative Site
Saint Petersburg, 191024
Novartis Investigative Site
Saratov, 410028
South Africa2 sites
Novartis Investigative Site
Parktown, 2193
Novartis Investigative Site
Pretoria, 0027
About this study
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
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.
- Conditions
- Multiple Myeloma
- Being tested
- Panobinostat, Bortezomib, Dexamethasone, Placebo
- Keywords
- Myeloma, DACi, Bortezomib, Combination, Panobinostat, LBH589D, relapsed, Velcade®, Combination,
- Medical subject headings
- Multiple Myeloma, Neoplasms, Plasma Cell, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PanobinostatDrug
Also called LBH589
Panobinostat was administered 3x week ( 2 weeks on 1 week off)
BortezomibDrug
Also called (Velcade®)
Bortezomib was administered 2 x week ( 2weeks on 1 week off)
DexamethasoneDrug
Dexamethasone was adminstered on day of Bortezomib and the day after Bortezomib administration
PlaceboDrug
Placebo was administered 3x week ( 2 weeks on 1 week off)
| Study group | Role | What they receive |
|---|---|---|
| Panobinostat + Bortezomib + Dexamethasone | Experimental | Not described Receives: Drug: Panobinostat; Drug: Bortezomib; Drug: Dexamethasone |
| Placebo + Bortezomib + Dexamethasone | Placebo comparator | Not described Receives: Drug: Bortezomib; Drug: Dexamethasone; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 45 months
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.
Measured: 45 months
Secondary outcomes (9)
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
Measured: 45 months
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
Measured: 45 months
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
Measured: 45 months
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.
Measured: 45 months
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.
Measured: 45 months
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.
Measured: 45 months
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.
Measured: 12, 24 and 48 weeks
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.
Measured: 12, 24 and 48 weeks
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.
Measured: 12, 24 and 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2009 (estimated)
- Study start21 Dec 2009
- Primary completion30 Jul 2015
- Study completion30 Jul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 767 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01023308
- Sponsor's protocol ID
- CLBH589D2308
- Other IDs
- 2009-015507-52, 2009
- Acronym
- PANORAMA-1
- Status last verified
- Mar 2020
- First submitted
- 30 Nov 2009
- Last updated
- 17 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 27751707San-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.
PubMed 27677481Richardson 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.
PubMed 26631116San-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.
PubMed 25242045
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01023308
- Acronym / sponsor ID
- PANORAMA-1 / CLBH589D2308
- Conditions
- Multiple Myeloma
- Keywords
- Myeloma, DACi, Bortezomib, Combination, Panobinostat, LBH589D, relapsed, Velcade®
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 767 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 21 Dec 2009 (actual)
- Primary completion
- 30 Jul 2015 (actual)
- Study completion
- 30 Jul 2015 (actual)
- First posted
- 2 Dec 2009 (estimated)
- Results
- Posted 23 Oct 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Panobinostat + Bortezomib + Dexamethasone | Experimental | Drug: Panobinostat, Drug: Bortezomib, Drug: Dexamethasone |
| Placebo + Bortezomib + Dexamethasone | Placebo comparator | Drug: Bortezomib, Drug: Dexamethasone, Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patient has a previous diagnosis of multiple myeloma.
- Patient requires retreatment for multiple myeloma
- Patient has measurable M component in serum or urine at study screening
Key exclusion criteria (8 listed)
- Patient who has progressed under all prior lines of anti MM therapy
- 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
- 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
- Patient received prior treatment with DAC inhibitors including panobinostat
- Patient has impaired cardiac function, or a prolonged QTc interval at screening ECG
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PanobinostatAlso: LBH589Panobinostat was administered 3x week ( 2 weeks on 1 week off) | Drug | Panobinostat + Bortezomib + Dexamethasone |
| BortezomibAlso: (Velcade®)Bortezomib was administered 2 x week ( 2weeks on 1 week off) | Drug | Panobinostat + Bortezomib + Dexamethasone, Placebo + Bortezomib + Dexamethasone |
| DexamethasoneDexamethasone was adminstered on day of Bortezomib and the day after Bortezomib administration | Drug | Panobinostat + Bortezomib + Dexamethasone, Placebo + Bortezomib + Dexamethasone |
| PlaceboPlacebo was administered 3x week ( 2 weeks on 1 week off) | Drug | Placebo + Bortezomib + Dexamethasone |
Primary outcome
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.
Time frame: 45 months
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.
Time frame: 45 months
9 secondary outcomes
Overall Survival in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone
Time frame: 45 months
Overall Survival in Patients Treated With Panobinostat in Combination With Bortezomib and Dexamethasone vs. Patients Treated by Placebo in Combination With Bortezomib and Dexamethasone
Time frame: 45 months
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.
Time frame: 45 months
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.
Time frame: 45 months
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.
Time frame: 45 months
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.
Time frame: 45 months
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC) QLQ-MY20-Change From Baseline by Treatment Group
Time frame: 12, 24 and 48 weeks
European Organization for Research and Treatment of Cancer Multiple Myeloma Module (EORTC ) QLQ-C30 - Summary Statistics by Treatment Group
Time frame: 12, 24 and 48 weeks
Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System : FACT/GOG-NTX-Change From Baseline by Treatment Group
Time frame: 12, 24 and 48 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27751707San-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.
- Derived from this study: PubMed 27677481San-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.
- Derived from this study: PubMed 26631116Richardson 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.
- Derived from this study: PubMed 25242045San-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.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
210 sites in 34 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Panobinostat, Bortezomib and Dexamethasone in people with Multiple Myeloma, run by Novartis Pharmaceuticals at 210 sites in 34 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 210 sites in United States, Germany, Japan, Italy, China and 29 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Oct 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 45 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01023308, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2020.