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Panobinostat/Bortezomib/Dexamethasone in Relapsed or Relapsed-and-refractory Multiple Myeloma (PANORAMA_3)

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ClinicalTrials.gov Identifier: NCT02654990
Recruitment Status : Recruiting
First Posted : January 13, 2016
Last Update Posted : March 5, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:

The purpose of this study is to investigate the safety and efficacy of three different regimens of PAN (20 mg TIW, 20 mg BIW, and 10 mg TIW) in combination with s.c. BTZ and Dex and to provide exposure, safety and efficacy data to identify the optimal regimen of PAN in a randomized, 3-arm parallel design. This study will also assess the impact of administering s.c. BTZ (in combination with PAN and Dex) twice weekly for 4 cycles, and then weekly starting from Cycle 5 until disease progression in patients ≤ 75 years of age. Patients > 75 years of age will receive for the entire treatment period s.c. BTZ weekly (in combination with PAN and Dex) until disease progression.

Patients will be treated until disease progression or until they discontinue earlier due to unacceptable toxicity or for other reasons.

Patients who discontinued study treatment for reasons other than disease progression will be followed for efficacy every 6 weeks.

All patients will be followed for survival until the last patient entering long-term follow-up has completed a 3 year survival follow-up or discontinued earlier.


Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: panobinostat capsules Drug: bortezomib injection Drug: dexamethasone tablets Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 240 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Open-label Phase 2 Study Evaluating the Safety and Efficacy of Three Different Regimens of Oral Panobinostat in Combination With Subcutaneous Bortezomib and Oral Dexamethasone in Patients With Relapsed or Relapsed/Refractory Multiple Myeloma Who Have Been Previously Exposed to Immunomodulatory Agents
Actual Study Start Date : April 27, 2016
Estimated Primary Completion Date : June 10, 2019
Estimated Study Completion Date : December 15, 2022


Arm Intervention/treatment
Experimental: Arm A - 20mg PAN TIW
20mg panobinostat three times a week, 2 weeks on/1week of in combination with s.c. bortezomib and p.o. dexamethasone
Drug: panobinostat capsules
20mg, 10mg or 15mg (for dose reductions only)
Other Name: PAN, LBH589

Drug: bortezomib injection
1.3mg/m2 sub-cutaneous administration; Cycle 1-4: 2 weeks on/1 week off twice a week for patients <=75 years at time of screening; once a week for patient > 75 years Cycle 5+: once a week for all patients
Other Name: BTZ

Drug: dexamethasone tablets
pre and 24h after BTZ administration; patients <= 75 years at time of screening: 20mg/dose patients > 75 years: 10mg/dose
Other Name: Dex

Experimental: Arm B - 20mg PAN BIW
20mg panobinostat twice a week, 2 weeks on/1 week off in combination with s.c. bortezomib and p.o. dexamethasone
Drug: panobinostat capsules
20mg, 10mg or 15mg (for dose reductions only)
Other Name: PAN, LBH589

Drug: bortezomib injection
1.3mg/m2 sub-cutaneous administration; Cycle 1-4: 2 weeks on/1 week off twice a week for patients <=75 years at time of screening; once a week for patient > 75 years Cycle 5+: once a week for all patients
Other Name: BTZ

Drug: dexamethasone tablets
pre and 24h after BTZ administration; patients <= 75 years at time of screening: 20mg/dose patients > 75 years: 10mg/dose
Other Name: Dex

Experimental: Arm C - 10mg PAN TIW
10mg panobinostat three times a week 2 weeks on/1 week off in combination with s.c. bortezomib and p.o. dexamethasone
Drug: panobinostat capsules
20mg, 10mg or 15mg (for dose reductions only)
Other Name: PAN, LBH589

Drug: bortezomib injection
1.3mg/m2 sub-cutaneous administration; Cycle 1-4: 2 weeks on/1 week off twice a week for patients <=75 years at time of screening; once a week for patient > 75 years Cycle 5+: once a week for all patients
Other Name: BTZ

Drug: dexamethasone tablets
pre and 24h after BTZ administration; patients <= 75 years at time of screening: 20mg/dose patients > 75 years: 10mg/dose
Other Name: Dex




Primary Outcome Measures :
  1. Overall response rate (ORR) up to 8 cycles [ Time Frame: up to 8 cycles per patient, approximately 30 months ]
    assessed according to IMWG guidelines


Secondary Outcome Measures :
  1. ORR throughout study [ Time Frame: approximately 70 months ]
  2. individual immunophenotypic complete response (CR) rate [ Time Frame: approximately 30 and 70 months ]
  3. Progression-free survival [ Time Frame: approximately 30 and 70 months ]
  4. Maximum plasma concentration (Cmax) for panobinostat (PAN) and bortezomib (BTZ) [ Time Frame: approximately 30 months ]
  5. Time to progression [ Time Frame: approximately 30 and 70 months ]
  6. Time to response [ Time Frame: approximately 30 and 70 months ]
  7. Duration of response (DOR) [ Time Frame: approximately 30 and 70 months ]
  8. European Organization of Research and Treatment of Cancer Quality of Life core 30-item questionnaire scores over time compared [ Time Frame: approximately 30 and 70 months ]
    EORTC QLQ-C30 on-treatment and in post treatment follow-up

  9. individual stringent CR rate [ Time Frame: approximately 30 and 70 months ]
  10. individual CR rate [ Time Frame: approximately 30 and 70 months ]
  11. overall survival [ Time Frame: approximately 30 and 70 months ]
  12. individual Very Good Partial Response rate [ Time Frame: approximately 30 and 70 months ]
  13. Functional Assessment of Cancer Therapy / Gynecologic Oncology Group - Neurotoxicity scale scores over time [ Time Frame: approximately 30 and 70 months ]
    FACT/GOG-Ntx on-treatment

  14. Time to reach Cmax for PAN and BTZ [ Time Frame: approximately 30 months ]
  15. Minimum observed plasma concentration (Cmin) for PAN and BTZ [ Time Frame: approximately 30 months ]
  16. Observed plasma concentration 24 hours after single and multiple dose administration of PAN and BTZ [ Time Frame: 24 hours after every dose, approximately 30 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • multiple myeloma as per IMWG 2014 definition
  • requiring treatment for relapsed or relapsed/refractory disease
  • measurable disease based on central protein assessment
  • 1 to 4 prior lines of therapy
  • prior IMiD exposure
  • acceptable lab values prior to randomization

Exclusion Criteria:

  • primary refractory myeloma
  • refractory to bortezomib
  • concomitant anti-cancer therapy (other then BTZ/Dex and bisphosphonates
  • prior treatment with DAC inhibitors
  • Clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months prior to randomization)
  • Unresolved diarrhea ≥ CTCAE grade 2 or presence of medical condition associated with chronic diarrhea (such as irritable bowel syndrome, inflammatory bowel disease)

Other protocol-defined inclusion/exclusion criteria may apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02654990


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com

  Hide Study Locations
Locations
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United States, Arkansas
Highlands Oncology Group Completed
Fayetteville, Arkansas, United States, 72703
United States, California
Los Angeles Hematology/Oncology Medical Group Wilson Terr Recruiting
Los Angeles, California, United States, 90017
Contact: Ruma Barva       rbarva@scoranet.org   
Principal Investigator: Boris Bagdasarian         
United States, Colorado
Poudre Valley Hospital SC Recruiting
Fort Collins, Colorado, United States, 80528
Contact: Tracey Way       tracey.way@uchealth.org   
Principal Investigator: Steven R. Schuster         
United States, Florida
UF Health Cancer Center Completed
Gainesville, Florida, United States, 32608
United States, Georgia
Emory University School of Medicine/Winship Cancer Institute Emory Univ - Winship Cancer Ct Completed
Atlanta, Georgia, United States, 30322
United States, Kentucky
University of Louisville Recruiting
Louisville, Kentucky, United States, 40202
Contact: Christa Baxter    502-217-8273    christa.baxter@louisville.edu   
Principal Investigator: Maxwell Krem         
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Diane Warren    617-632-3352    Diane_Warren@dfci.harvard.edu   
Principal Investigator: Jacob Laubach         
United States, New York
Clinical Research Alliance Recruiting
Lake Success, New York, United States, 11042
Contact: Colleen Kats    516-488-2918    ckats@researchcra.com   
Principal Investigator: Morton Coleman         
United States, Washington
Providence Regional Cancer Partnership The Everett Clinic Completed
Everett, Washington, United States, 98201
United States, West Virginia
West Virginia University/ Mary Babb Randolph Cancer Center West Virgina University Recruiting
Morgantown, West Virginia, United States, 26506
Contact: Valerie Phillips       vphillip@hsc.wvu.edu   
Principal Investigator: Abraham Kanate         
Australia, Victoria
Novartis Investigative Site Active, not recruiting
Prahran, Victoria, Australia, 3181
Belgium
Novartis Investigative Site Recruiting
Hasselt, Belgium, 3500
Novartis Investigative Site Completed
Yvoir, Belgium, 5530
Brazil
Novartis Investigative Site Active, not recruiting
Barretos, Sao Paulo, Brazil, 14784 400
Novartis Investigative Site Active, not recruiting
Sao Paulo, SP, Brazil, 04537 081
Novartis Investigative Site Active, not recruiting
Sao Paulo, Brazil, 05403-000
Canada, Alberta
Novartis Investigative Site Completed
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Ontario
Novartis Investigative Site Completed
Kitchener, Ontario, Canada, N2G 1G3
Czechia
Novartis Investigative Site Active, not recruiting
Ostrava Poruba, Czech Republic, Czechia, 708 52
Novartis Investigative Site Active, not recruiting
Praha, Czechia, 12808
France
Novartis Investigative Site Active, not recruiting
Bayonne, Bayonne Cedex, France, 64109
Novartis Investigative Site Active, not recruiting
Avignon cedex 9, France, 84902
Novartis Investigative Site Active, not recruiting
Grenoble, France, 38043
Novartis Investigative Site Active, not recruiting
La Roche sur Yon Cedex, France, 85295
Novartis Investigative Site Withdrawn
Lille, France, 59037
Novartis Investigative Site Active, not recruiting
Metz, France, 57000
Novartis Investigative Site Withdrawn
Montpellier cedex 5, France, 34295
Novartis Investigative Site Active, not recruiting
Nantes Cedex 1, France, 44093
Novartis Investigative Site Active, not recruiting
Paris, France, 75231
Novartis Investigative Site Withdrawn
Pessac, France, 33604
Germany
Novartis Investigative Site Active, not recruiting
Bad Saarow, Germany, 15526
Novartis Investigative Site Active, not recruiting
Bayreuth, Germany, 95445
Novartis Investigative Site Active, not recruiting
Darmstadt, Germany, 64287
Novartis Investigative Site Active, not recruiting
Dresden, Germany, 01307
Novartis Investigative Site Withdrawn
Essen, Germany, 45147
Novartis Investigative Site Completed
Halle Saale, Germany, 06120
Novartis Investigative Site Active, not recruiting
Hamburg, Germany, 22763
Novartis Investigative Site Completed
Kiel, Germany, 24105
Novartis Investigative Site Active, not recruiting
Leipzig, Germany, 04103
Novartis Investigative Site Withdrawn
Magdeburg, Germany, 39120
Greece
Novartis Investigative Site Active, not recruiting
Athens, Greece, 115 27
Novartis Investigative Site Active, not recruiting
Athens, Greece, 115 28
Novartis Investigative Site Active, not recruiting
Patras, Greece, 265 00
Hungary
Novartis Investigative Site Active, not recruiting
Debrecen, HUN, Hungary, 4032
Novartis Investigative Site Active, not recruiting
Budapest, Hungary, 1097
Novartis Investigative Site Active, not recruiting
Kaposvar, Hungary, 7400
Novartis Investigative Site Active, not recruiting
Nyiregyhaza, Hungary, 4400
Italy
Novartis Investigative Site Withdrawn
Bologna, BO, Italy, 40138
Novartis Investigative Site Withdrawn
Cagliari, CA, Italy, 09126
Novartis Investigative Site Withdrawn
Pescara, PE, Italy, 65124
Novartis Investigative Site Active, not recruiting
Roma, RM, Italy, 00161
Novartis Investigative Site Active, not recruiting
Rimini, RN, Italy, 47900
Novartis Investigative Site Withdrawn
Torino, TO, Italy, 10126
Korea, Republic of
Novartis Investigative Site Completed
Seoul, Gyeonggi Do, Korea, Republic of, 03080
Novartis Investigative Site Recruiting
Hwasun-gun, Jeollanam-do, Korea, Republic of, 58128
Lebanon
Novartis Investigative Site Active, not recruiting
Ashrafieh, Lebanon, 166830
Novartis Investigative Site Active, not recruiting
Beirut, Lebanon
Novartis Investigative Site Active, not recruiting
Saida, Lebanon, 652
Netherlands
VUmc, Hematology, PK2 BR012 Recruiting
Amsterdam, Netherlands, 1081 HV
Contact: N.W.C.J. van de Donk    00 31 20 4442604    n.vandedonk@vumc.nl   
Albert Schweitzer ziekenhuis, Hematology Recruiting
Dordrecht, Netherlands, 3318 AT
Contact: M.D. Levin    +31 786523787    m-d.levin@asz.nl   
Norway
Novartis Investigative Site Active, not recruiting
Oslo, Norway, NO-0424
Poland
Novartis Investigative Site Active, not recruiting
Lublin, Poland, 20 090
Novartis Investigative Site Active, not recruiting
Torun, Poland, 87 100
Novartis Investigative Site Active, not recruiting
Warszawa, Poland, 02 106
Novartis Investigative Site Active, not recruiting
Warszawa, Poland, 02 776
Novartis Investigative Site Active, not recruiting
Wroclaw, Poland, 50 367
Portugal
Novartis Investigative Site Active, not recruiting
Braga, Portugal, 4710243
Novartis Investigative Site Active, not recruiting
Porto, Portugal, 4200-072
Russian Federation
Novartis Investigative Site Completed
Saint Petersburg, Russian Federation, 191024
Novartis Investigative Site Active, not recruiting
Saratov, Russian Federation, 410012
Spain
Novartis Investigative Site Recruiting
Malaga, Andalucia, Spain, 29010
Novartis Investigative Site Recruiting
Sabadell, Barcelona, Spain, 08208
Novartis Investigative Site Active, not recruiting
Salamanca, Castilla Y Leon, Spain, 37007
Novartis Investigative Site Completed
Badalona, Catalunya, Spain, 08916
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08036
Novartis Investigative Site Recruiting
L Hospitalet De Llobregat, Catalunya, Spain, 08907
Novartis Investigative Site Recruiting
Valencia, Comunidad Valenciana, Spain, 46017
Novartis Investigative Site Completed
Pamplona, Navarra, Spain, 31008
Novartis Investigative Site Active, not recruiting
La Laguna, Santa Cruz De Tenerife, Spain, 38320
Novartis Investigative Site Completed
Madrid, Spain, 28006
Novartis Investigative Site Completed
Madrid, Spain, 28040
Novartis Investigative Site Active, not recruiting
Madrid, Spain, 28041
Novartis Investigative Site Completed
Zaragoza, Spain, 50009
Sweden
Novartis Investigative Site Active, not recruiting
Lulea, Sweden, SE 971 80
Novartis Investigative Site Active, not recruiting
Lund, Sweden, SE-221 85
Novartis Investigative Site Active, not recruiting
Uppsala, Sweden, SE-751 85
Thailand
Novartis Investigative Site Active, not recruiting
Bangkok, Thailand, 10330
Novartis Investigative Site Active, not recruiting
Chiang Mai, Thailand, 50200
Novartis Investigative Site Active, not recruiting
Muang, Thailand, 40002
Turkey
Novartis Investigative Site Recruiting
Ankara, Turkey, 06100
Novartis Investigative Site Recruiting
Izmir, Turkey, 35340
Novartis Investigative Site Recruiting
Pendik / Istanbul, Turkey, 34899
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02654990     History of Changes
Other Study ID Numbers: CLBH589D2222
First Posted: January 13, 2016    Key Record Dates
Last Update Posted: March 5, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
multiple myeloma
relapsed or relapsed/refractory
LBH589
panobinostat
bortezomib
dexamethasone

Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Dexamethasone acetate
Bortezomib
Panobinostat
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents