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

NCT02654990 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CLBH589D22222015-001564-19
• Study Type: interventional
• Target: 248
• Locations: 22 countries
• Sites: 80

Brief Summary

Note: The study data was transferred to zr pharma\& following the divestment of panobinostat to pharma\&. Prior to study completion under the sponsorship of Secura Bio, the study was initiated and conducted in part under the sponsorship of Novartis. The purpose of this study is to investigate the safety and efficacy of 3 different regimens of panobinostat (20 milligrams \[mg\] thrice a week \[TIW\], 20 mg twice a week \[BIW\], and 10 mg TIW) in combination with subcutaneous bortezomib and dexamethasone and to provide exposure, safety and efficacy data to identify the optimal regimen of panobinostat in a randomized, 3-arm parallel design. This study will also assess the impact of administering subcutaneous bortezomib (in combination with panobinostat and dexamethasone) twice weekly for 4 cycles, and then weekly starting from Cycle 5 until disease progression in participants ≤ 75 years of age. Participants \> 75 years of age will receive subcutaneous bortezomib weekly for the entire treatment period (in combination with panobinostat and dexamethasone) until disease progression. Participants will be treated until disease progression or until they discontinue earlier due to unacceptable toxicity or for other reasons. Participants who discontinued study treatment for reasons other than disease progression will be followed for efficacy every 6 weeks. All participants will be followed for survival until the last participant entering long-term follow-up has completed a 3-year survival follow-up or discontinued earlier.

Conditions

Multiple Myeloma

Keywords

multiple myeloma; relapsed or relapsed/refractory; LBH589; panobinostat; bortezomib; dexamethasone

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  ORR is defined as the percentage of participants with a confirmed partial response (PR) or better (immunophenotypic complete response \[iCR\] or stringent complete response \[sCR\] or complete response \[CR\] or very good partial response \[VGPR\]) as their best overall response after completion of up to 8 cycles of assigned study regimen. Each cycle was 21 days long. Best overall response was the best post-baseline confirmed overall response observed in a given participant and was determined based on overall responses observed at all post-baseline response assessments, recorded from randomization until progressive disease (PD), death, start of new therapy, withdrawal of consent, or end of study, whatever came first. ORR was assessed blindly per independent review committee (IRC) according to International Myeloma Working Group (IMWG) criteria.

  Up to 168 days

Secondary Outcomes (17)

• ORR Throughout the Study

  Up to 5.2 years

• iCR Rate

  Up to 5.2 years

• sCR Rate

  Up to 5.2 years

• CR Rate

  Up to 5.2 years

• VGPR Rate

  Up to 5.2 years

Study Arms (3)

Arm A - 20 mg Panobinostat TIW

EXPERIMENTAL

20 mg panobinostat TIW, 2 weeks on/1 week off in combination with subcutaneous bortezomib and per oral dexamethasone

Drug: Panobinostat Capsules; Drug: Bortezomib Injection; Drug: Dexamethasone tablets

Arm B - 20 mg Panobinostat BIW

EXPERIMENTAL

20 mg panobinostat BIW, 2 weeks on/1 week off in combination with subcutaneous bortezomib and per oral dexamethasone

Drug: Panobinostat Capsules; Drug: Bortezomib Injection; Drug: Dexamethasone tablets

Arm C - 10 mg Panobinostat TIW

EXPERIMENTAL

10 mg panobinostat TIW, 2 weeks on/1 week off in combination with subcutaneous bortezomib and per oral dexamethasone

Drug: Panobinostat Capsules; Drug: Bortezomib Injection; Drug: Dexamethasone tablets

Interventions

Panobinostat Capsules DRUG

20 mg, 10 mg or 15 mg (for dose reductions only)

Also known as: PAN, LBH589, Farydak

Arm A - 20 mg Panobinostat TIW; Arm B - 20 mg Panobinostat BIW; Arm C - 10 mg Panobinostat TIW

Bortezomib Injection DRUG

1.3 mg/square meter subcutaneous administration. Cycle 1-4: 2 weeks on/1 week off, BIW for participants ≤ 75 years at time of screening; once a week for participants \> 75 years. Cycle 5+: once a week for all participants.

Also known as: BTZ, Velcade

Arm A - 20 mg Panobinostat TIW; Arm B - 20 mg Panobinostat BIW; Arm C - 10 mg Panobinostat TIW

Dexamethasone tablets DRUG

Pre and 24 hours after bortezomib administration. Participants ≤ 75 years at time of screening: 20 mg/dose participants; \> 75 years: 10 mg/dose.

Also known as: Dex, Decadron

Arm A - 20 mg Panobinostat TIW; Arm B - 20 mg Panobinostat BIW; Arm C - 10 mg Panobinostat TIW

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• multiple myeloma per International Myeloma Working Group 2014 definition
• requiring treatment for relapsed or relapsed/refractory disease
• measurable disease based on central protein assessment
• received 1 to 4 prior lines of therapy
• prior immunomodulatory agent(s) exposure
• acceptable lab values prior to randomization

You may not qualify if:

• primary refractory myeloma
• refractory to bortezomib
• concomitant anti-cancer therapy (other than bortezomib/dexamethasone and bisphosphonates)
• prior treatment with pan-deacetylase inhibitors
• clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months prior to randomization)
• unresolved diarrhea ≥ Common Terminology Criteria for adverse events grade 2 or presence of medical condition associated with chronic diarrhea (such as irritable bowel syndrome and inflammatory bowel disease)

Sponsors & Collaborators

• pharmaand GmbH: lead

Study Sites (80)

Novartis Investigative Site

Fayetteville, Arkansas, 72703, United States

Location

Novartis Investigative Site

Los Angeles, California, 90017, United States

Location

Novartis Investigative Site

Fort Collins, Colorado, 80528, United States

Location

Novartis Investigative Site

Gainesville, Florida, 32608, United States

Location

Novartis Investigative Site

Atlanta, Georgia, 30322, United States

Location

Novartis Investigative Site

Louisville, Kentucky, 40202, United States

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Novartis Investigative Site

Boston, Massachusetts, 02215, United States

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Novartis Investigative Site

Lake Success, New York, 11042, United States

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Novartis Investigative Site

Morgantown, West Virginia, 26506, United States

Location

Novartis Investigative Site

Prahran, Victoria, 3181, Australia

Location

Novartis Investigative Site

Hasselt, 3500, Belgium

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Novartis Investigative Site

Barretos, São Paulo, 14784 400, Brazil

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Novartis Investigative Site

São Paulo, São Paulo, 04537 081, Brazil

Location

Novartis Investigative Site

São Paulo, 05403-000, Brazil

Location

Novartis Investigative Site

Edmonton, Alberta, T6G 1Z2, Canada

Location

Novartis Investigative Site

Kitchener, Ontario, N2G 1G3, Canada

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Novartis Investigative Site

Ostrava Poruba, Czech Republic, 708 52, Czechia

Location

Novartis Investigative Site

Prague, 12808, Czechia

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Novartis Investigative Site

Bayonne, Bayonne Cedex, 64109, France

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Novartis Investigative Site

Avignon, 84902, France

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Novartis Investigative Site

Grenoble, 38043, France

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Novartis Investigative Site

La Roche-sur-Yon, 85295, France

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Novartis Investigative Site

Lille, 59037, France

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Novartis Investigative Site

Metz, 57000, France

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Novartis Investigative Site

Nantes, 44093, France

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Novartis Investigative Site

Paris, 75231, France

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Novartis Investigative Site

Pessac, 33604, France

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Novartis Investigative Site

Bad Saarow, 15526, Germany

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Novartis Investigative Site

Bayreuth, 95445, Germany

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Novartis Investigative Site

Darmstadt, 64287, Germany

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Novartis Investigative Site

Dresden, 01307, Germany

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Novartis Investigative Site

Halle, 06120, Germany

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Novartis Investigative Site

Hamburg, 22763, Germany

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Novartis Investigative Site

Kiel, 24105, Germany

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Novartis Investigative Site

Leipzig, 04103, Germany

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Novartis Investigative Site

Athens, 115 27, Greece

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Novartis Investigative Site

Athens, 115 28, Greece

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Novartis Investigative Site

Pátrai, 265 00, Greece

Location

Novartis Investigative Site

Debrecen, HUN, 4032, Hungary

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Novartis Investigative Site

Budapest, 1097, Hungary

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Novartis Investigative Site

Kaposvár, 7400, Hungary

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Novartis Investigative Site

Nyíregyháza, 4400, Hungary

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Novartis Investigative Site

Roma, RM, 00161, Italy

Location

Novartis Investigative Site

Rimini, RN, 47900, Italy

Location

Novartis Investigative Site

Beirut, 166830, Lebanon

Location

Novartis Investigative Site

Beirut, Lebanon

Location

Novartis Investigative Site

Sidon, 652, Lebanon

Location

VUmc, Hematology, PK2 BR012

Amsterdam, 1081 HV, Netherlands

Location

Albert Schweitzer ziekenhuis, Hematology

Dordrecht, 3318 AT, Netherlands

Location

Novartis Investigative Site

Oslo, NO 0450, Norway

Location

Novartis Investigative Site

Lublin, 20 090, Poland

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Novartis Investigative Site

Torun, 87 100, Poland

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Novartis Investigative Site

Warsaw, 02 106, Poland

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Novartis Investigative Site

Warsaw, 02 776, Poland

Location

Novartis Investigative Site

Wroclaw, 50 367, Poland

Location

Novartis Investigative Site

Braga, 4710243, Portugal

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Novartis Investigative Site

Porto, 4200-072, Portugal

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Novartis Investigative Site

Saint Petersburg, 191024, Russia

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Novartis Investigative Site

Saratov, 410012, Russia

Location

Novartis Investigative Site

Hwasun, 58128, South Korea

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Málaga, Andalusia, 29010, Spain

Location

Novartis Investigative Site

Salamanca, Castille and León, 37007, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Catalonia, 08907, Spain

Location

Novartis Investigative Site

San Cristóbal de La Laguna, Santa Cruz De Tenerife, 38320, Spain

Location

Novartis Investigative Site

Madrid, 28006, Spain

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Novartis Investigative Site

Madrid, 28040, Spain

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Novartis Investigative Site

Madrid, 28041, Spain

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Novartis Investigative Site

Zaragoza, 50009, Spain

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Novartis Investigative Site

Luleå, SE 971 80, Sweden

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Novartis Investigative Site

Lund, SE-221 85, Sweden

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Novartis Investigative Site

Uppsala, SE-751 85, Sweden

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Novartis Investigative Site

Nonthaburi, Muang, 40002, Thailand

Location

Novartis Investigative Site

Bangkok, 10330, Thailand

Location

Novartis Investigative Site

Chiang Mai, 50200, Thailand

Location

Novartis Investigative Site

Ankara, 06100, Turkey (Türkiye)

Location

Novartis Investigative Site

Istanbul, 34899, Turkey (Türkiye)

Location

Novartis Investigative Site

Izmir, 35340, Turkey (Türkiye)

Location

Related Publications (1)

• Laubach JP, Schjesvold F, Mariz M, Dimopoulos MA, Lech-Maranda E, Spicka I, Hungria VTM, Shelekhova T, Abdo A, Jacobasch L, Polprasert C, Hajek R, Illes A, Wrobel T, Sureda A, Beksac M, Goncalves IZ, Blade J, Rajkumar SV, Chari A, Lonial S, Spencer A, Maison-Blanche P, Moreau P, San-Miguel JF, Richardson PG. Efficacy and safety of oral panobinostat plus subcutaneous bortezomib and oral dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma (PANORAMA 3): an open-label, randomised, phase 2 study. Lancet Oncol. 2021 Jan;22(1):142-154. doi: 10.1016/S1470-2045(20)30680-X. Epub 2020 Dec 7.

  PMID: 33301738 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

Panobinostat; Bortezomib; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Medical Information Department
• Organization: pharmaand GmbH

medinfo@pharmaand.com

+43/1/3560006

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2015
• First Posted: January 13, 2016
• Study Start: April 27, 2016
• Primary Completion: October 18, 2019
• Study Completion: August 15, 2022
• Last Updated: July 12, 2024
• Results First Posted: July 12, 2024

Record last verified: 2024-07

Locations

BR (3); AU (1); US (9); BE (1); CZ (2); KR (2); TU (3); FR (9); RU (2); TH (3); SE (3); DE (8); NL (2); PL (5); HU (4); PT (2); ES (10); CA (2); GR (3); IT (2); NO (1); LE (3)