Clinical trial NCT02654990: Panobinostat/Bortezomib/Dexamethasone in Relapsed or Relapsed-and-refractory Multiple Myeloma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: multiple myeloma
relapsed or relapsed/refractory
LBH589
panobinostat
bortezomib
dexamethasone
Lead sponsor: pharmaand GmbH
Sponsor class: INDUSTRY
First posted: 2016-01-13
Enrollment: 248
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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)

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 168 days
Secondary outcomes:
measure: ORR Throughout the Study
timeFrame: Up to 5.2 years
measure: iCR Rate
timeFrame: Up to 5.2 years
measure: sCR Rate
timeFrame: Up to 5.2 years
measure: CR Rate
timeFrame: Up to 5.2 years
measure: VGPR Rate
timeFrame: Up to 5.2 years
measure: Progression-free Survival (PFS)
timeFrame: Up to 5.2 years
measure: Overall Survival (OS)
timeFrame: Up to 5.2 years
measure: Maximum Plasma Concentration (Cmax): Panobinostat
timeFrame: Cycle 1 Day 1 (Pre-dose, up to 8 hours post dose)
measure: Cmax: Bortezomib
timeFrame: Cycle 1 Day 1 (Pre-dose, up to 8 hours post dose)
measure: Time to Reach Cmax (Tmax): Panobinostat
timeFrame: Cycle 1 Day 1 (Pre-dose, up to 8 hours post dose)
measure: Tmax: Bortezomib
timeFrame: Cycle 1 Day 1 (Pre-dose, up to 8 hours post dose)
measure: Exposure Response: Cmax for Panobinostat
timeFrame: Up to 5.2 Years
measure: Change From Baseline in European Organization of Research and Treatment of Cancer (EORTC) Quality of Life Core 30-item Questionnaire (QLQ-C30) Global Health Status (GHS) Score
timeFrame: Cycle 15 Day 1, at approximately 295 days
measure: Change From Baseline in the Functional Assessment of Cancer Therapy (FACT)/Gynecologic Oncology Group-Neurotoxicity (GOG-Ntx) Neurotoxicity Subscale Score
timeFrame: Cycle 15 Day 1, at approximately 295 days
measure: Time to Progression (TTP)
timeFrame: Up to 5.2 years
measure: Time to Response (TTR)
timeFrame: Up to 5.2 years
measure: Duration of Response (DOR)
timeFrame: Up to 5.2 years
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Novartis Investigative Site
state: Arkansas
city: Los Angeles
country: United States
facility: Novartis Investigative Site
state: California
city: Fort Collins
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Gainesville
country: United States
facility: Novartis Investigative Site
state: Florida
city: Atlanta
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Louisville
country: United States
facility: Novartis Investigative Site
state: Kentucky
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Lake Success
country: United States
facility: Novartis Investigative Site
state: New York
city: Morgantown
country: United States
facility: Novartis Investigative Site
state: West Virginia
city: Prahran
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Hasselt
country: Belgium
facility: Novartis Investigative Site
city: Barretos
country: Brazil
facility: Novartis Investigative Site
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
city: Edmonton
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Kitchener
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Ostrava Poruba
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Praha
country: Czechia
facility: Novartis Investigative Site
city: Bayonne
country: France
facility: Novartis Investigative Site
state: Bayonne Cedex
city: Avignon Cedex 9
country: France
facility: Novartis Investigative Site
city: Grenoble
country: France
facility: Novartis Investigative Site
city: La Roche sur Yon Cedex
country: France
facility: Novartis Investigative Site
city: Lille
country: France
facility: Novartis Investigative Site
city: Metz
country: France
facility: Novartis Investigative Site
city: Nantes Cedex 1
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Pessac
country: France
facility: Novartis Investigative Site
city: Bad Saarow
country: Germany
facility: Novartis Investigative Site
city: Bayreuth
country: Germany
facility: Novartis Investigative Site
city: Darmstadt
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Halle Saale
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Kiel
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Patras
country: Greece
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
state: HUN
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Kaposvar
country: Hungary
facility: Novartis Investigative Site
city: Nyiregyhaza
country: Hungary
facility: Novartis Investigative Site
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Rimini
country: Italy
facility: Novartis Investigative Site
state: RN
city: Hwasun
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Beirut
country: Lebanon
facility: Novartis Investigative Site
city: Beirut
country: Lebanon
facility: Novartis Investigative Site
city: Sidon
country: Lebanon
facility: Novartis Investigative Site
city: Amsterdam
country: Netherlands
facility: VUmc, Hematology, PK2 BR012
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer ziekenhuis, Hematology
city: Oslo
country: Norway
facility: Novartis Investigative Site
city: Lublin
country: Poland
facility: Novartis Investigative Site
city: Torun
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Wroclaw
country: Poland
facility: Novartis Investigative Site
city: Braga
country: Portugal
facility: Novartis Investigative Site
city: Porto
country: Portugal
facility: Novartis Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Saratov
country: Russian Federation
facility: Novartis Investigative Site
city: Malaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Salamanca
country: Spain
facility: Novartis Investigative Site
state: Castilla Y Leon
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: L'Hospitalet De Llobregat
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: La Laguna
country: Spain
facility: Novartis Investigative Site
state: Santa Cruz De Tenerife
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Zaragoza
country: Spain
facility: Novartis Investigative Site
city: Lulea
country: Sweden
facility: Novartis Investigative Site
city: Lund
country: Sweden
facility: Novartis Investigative Site
city: Uppsala
country: Sweden
facility: Novartis Investigative Site
city: Mueang Nonthaburi
country: Thailand
facility: Novartis Investigative Site
state: Muang
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Chiang Mai
country: Thailand
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
Study officials:
References:
citation: 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.