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

Primary Purpose

Multiple Myeloma

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
panobinostat capsules
bortezomib injection
dexamethasone tablets
Sponsored by
pharmaand GmbH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring multiple myeloma, relapsed or relapsed/refractory, LBH589, panobinostat, bortezomib, dexamethasone

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
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  • Novartis Investigative Site
  • Novartis Investigative Site
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  • Novartis Investigative Site
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  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • VUmc, Hematology, PK2 BR012
  • Albert Schweitzer ziekenhuis, Hematology
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
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  • Novartis Investigative Site
  • Novartis Investigative Site
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  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Arm A - 20mg PAN TIW

Arm B - 20mg PAN BIW

Arm C - 10mg PAN TIW

Arm Description

20mg panobinostat three times a week, 2 weeks on/1week of in combination with s.c. bortezomib and p.o. dexamethasone

20mg panobinostat twice a week, 2 weeks on/1 week off in combination with s.c. bortezomib and p.o. dexamethasone

10mg panobinostat three times a week 2 weeks on/1 week off in combination with s.c. bortezomib and p.o. dexamethasone

Outcomes

Primary Outcome Measures

Overall response rate (ORR) up to 8 cycles
assessed according to IMWG guidelines

Secondary Outcome Measures

ORR throughout study
individual immunophenotypic complete response (CR) rate
Progression-free survival
Maximum plasma concentration (Cmax) for panobinostat (PAN) and bortezomib (BTZ)
Time to progression
Time to response
Duration of response (DOR)
European Organization of Research and Treatment of Cancer Quality of Life core 30-item questionnaire scores over time compared
EORTC QLQ-C30 on-treatment and in post treatment follow-up
individual stringent CR rate
individual CR rate
overall survival
individual Very Good Partial Response rate
Functional Assessment of Cancer Therapy / Gynecologic Oncology Group - Neurotoxicity scale scores over time
FACT/GOG-Ntx on-treatment
Time to reach Cmax for PAN and BTZ
Minimum observed plasma concentration (Cmin) for PAN and BTZ
Observed plasma concentration 24 hours after single and multiple dose administration of PAN and BTZ

Full Information

First Posted
December 16, 2015
Last Updated
July 12, 2023
Sponsor
pharmaand GmbH
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1. Study Identification

Unique Protocol Identification Number
NCT02654990
Brief Title
Panobinostat/Bortezomib/Dexamethasone in Relapsed or Relapsed-and-refractory Multiple Myeloma
Acronym
PANORAMA_3
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

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
April 27, 2016 (Actual)
Primary Completion Date
October 18, 2019 (Actual)
Study Completion Date
August 15, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
pharmaand GmbH

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
NOTE: The study data was transferred to zr pharma& following the divestment of Panobinostat to pharma&. The study itself was conducted and completed under the sponsorship of Novartis. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
multiple myeloma, relapsed or relapsed/refractory, LBH589, panobinostat, bortezomib, dexamethasone

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
249 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A - 20mg PAN TIW
Arm Type
Experimental
Arm Description
20mg panobinostat three times a week, 2 weeks on/1week of in combination with s.c. bortezomib and p.o. dexamethasone
Arm Title
Arm B - 20mg PAN BIW
Arm Type
Experimental
Arm Description
20mg panobinostat twice a week, 2 weeks on/1 week off in combination with s.c. bortezomib and p.o. dexamethasone
Arm Title
Arm C - 10mg PAN TIW
Arm Type
Experimental
Arm Description
10mg panobinostat three times a week 2 weeks on/1 week off in combination with s.c. bortezomib and p.o. dexamethasone
Intervention Type
Drug
Intervention Name(s)
panobinostat capsules
Other Intervention Name(s)
PAN, LBH589
Intervention Description
20mg, 10mg or 15mg (for dose reductions only)
Intervention Type
Drug
Intervention Name(s)
bortezomib injection
Other Intervention Name(s)
BTZ
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
dexamethasone tablets
Other Intervention Name(s)
Dex
Intervention Description
pre and 24h after BTZ administration; patients <= 75 years at time of screening: 20mg/dose patients > 75 years: 10mg/dose
Primary Outcome Measure Information:
Title
Overall response rate (ORR) up to 8 cycles
Description
assessed according to IMWG guidelines
Time Frame
up to 8 cycles per patient, approximately 30 months
Secondary Outcome Measure Information:
Title
ORR throughout study
Time Frame
approximately 70 months
Title
individual immunophenotypic complete response (CR) rate
Time Frame
approximately 30 and 70 months
Title
Progression-free survival
Time Frame
approximately 30 and 70 months
Title
Maximum plasma concentration (Cmax) for panobinostat (PAN) and bortezomib (BTZ)
Time Frame
approximately 30 months
Title
Time to progression
Time Frame
approximately 30 and 70 months
Title
Time to response
Time Frame
approximately 30 and 70 months
Title
Duration of response (DOR)
Time Frame
approximately 30 and 70 months
Title
European Organization of Research and Treatment of Cancer Quality of Life core 30-item questionnaire scores over time compared
Description
EORTC QLQ-C30 on-treatment and in post treatment follow-up
Time Frame
approximately 30 and 70 months
Title
individual stringent CR rate
Time Frame
approximately 30 and 70 months
Title
individual CR rate
Time Frame
approximately 30 and 70 months
Title
overall survival
Time Frame
approximately 30 and 70 months
Title
individual Very Good Partial Response rate
Time Frame
approximately 30 and 70 months
Title
Functional Assessment of Cancer Therapy / Gynecologic Oncology Group - Neurotoxicity scale scores over time
Description
FACT/GOG-Ntx on-treatment
Time Frame
approximately 30 and 70 months
Title
Time to reach Cmax for PAN and BTZ
Time Frame
approximately 30 months
Title
Minimum observed plasma concentration (Cmin) for PAN and BTZ
Time Frame
approximately 30 months
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Facility Information:
Facility Name
Novartis Investigative Site
City
Fayetteville
State/Province
Arkansas
ZIP/Postal Code
72703
Country
United States
Facility Name
Novartis Investigative Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90017
Country
United States
Facility Name
Novartis Investigative Site
City
Fort Collins
State/Province
Colorado
ZIP/Postal Code
80528
Country
United States
Facility Name
Novartis Investigative Site
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32608
Country
United States
Facility Name
Novartis Investigative Site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Novartis Investigative Site
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Novartis Investigative Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Novartis Investigative Site
City
Lake Success
State/Province
New York
ZIP/Postal Code
11042
Country
United States
Facility Name
Novartis Investigative Site
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States
Facility Name
Novartis Investigative Site
City
Prahran
State/Province
Victoria
ZIP/Postal Code
3181
Country
Australia
Facility Name
Novartis Investigative Site
City
Hasselt
ZIP/Postal Code
3500
Country
Belgium
Facility Name
Novartis Investigative Site
City
Barretos
State/Province
Sao Paulo
ZIP/Postal Code
14784 400
Country
Brazil
Facility Name
Novartis Investigative Site
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
04537 081
Country
Brazil
Facility Name
Novartis Investigative Site
City
Sao Paulo
ZIP/Postal Code
05403-000
Country
Brazil
Facility Name
Novartis Investigative Site
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
Novartis Investigative Site
City
Kitchener
State/Province
Ontario
ZIP/Postal Code
N2G 1G3
Country
Canada
Facility Name
Novartis Investigative Site
City
Ostrava Poruba
State/Province
Czech Republic
ZIP/Postal Code
708 52
Country
Czechia
Facility Name
Novartis Investigative Site
City
Praha
ZIP/Postal Code
12808
Country
Czechia
Facility Name
Novartis Investigative Site
City
Bayonne
State/Province
Bayonne Cedex
ZIP/Postal Code
64109
Country
France
Facility Name
Novartis Investigative Site
City
Avignon cedex 9
ZIP/Postal Code
84902
Country
France
Facility Name
Novartis Investigative Site
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
Novartis Investigative Site
City
La Roche sur Yon Cedex
ZIP/Postal Code
85295
Country
France
Facility Name
Novartis Investigative Site
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Novartis Investigative Site
City
Metz
ZIP/Postal Code
57000
Country
France
Facility Name
Novartis Investigative Site
City
Nantes Cedex 1
ZIP/Postal Code
44093
Country
France
Facility Name
Novartis Investigative Site
City
Paris
ZIP/Postal Code
75231
Country
France
Facility Name
Novartis Investigative Site
City
Pessac
ZIP/Postal Code
33604
Country
France
Facility Name
Novartis Investigative Site
City
Bad Saarow
ZIP/Postal Code
15526
Country
Germany
Facility Name
Novartis Investigative Site
City
Bayreuth
ZIP/Postal Code
95445
Country
Germany
Facility Name
Novartis Investigative Site
City
Darmstadt
ZIP/Postal Code
64287
Country
Germany
Facility Name
Novartis Investigative Site
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Novartis Investigative Site
City
Halle Saale
ZIP/Postal Code
06120
Country
Germany
Facility Name
Novartis Investigative Site
City
Hamburg
ZIP/Postal Code
22763
Country
Germany
Facility Name
Novartis Investigative Site
City
Kiel
ZIP/Postal Code
24105
Country
Germany
Facility Name
Novartis Investigative Site
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Novartis Investigative Site
City
Athens
ZIP/Postal Code
115 27
Country
Greece
Facility Name
Novartis Investigative Site
City
Athens
ZIP/Postal Code
115 28
Country
Greece
Facility Name
Novartis Investigative Site
City
Patras
ZIP/Postal Code
265 00
Country
Greece
Facility Name
Novartis Investigative Site
City
Debrecen
State/Province
HUN
ZIP/Postal Code
4032
Country
Hungary
Facility Name
Novartis Investigative Site
City
Budapest
ZIP/Postal Code
1097
Country
Hungary
Facility Name
Novartis Investigative Site
City
Kaposvar
ZIP/Postal Code
7400
Country
Hungary
Facility Name
Novartis Investigative Site
City
Nyiregyhaza
ZIP/Postal Code
4400
Country
Hungary
Facility Name
Novartis Investigative Site
City
Roma
State/Province
RM
ZIP/Postal Code
00161
Country
Italy
Facility Name
Novartis Investigative Site
City
Rimini
State/Province
RN
ZIP/Postal Code
47900
Country
Italy
Facility Name
Novartis Investigative Site
City
Hwasun-gun
State/Province
Jeollanam-do
ZIP/Postal Code
58128
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Beirut
ZIP/Postal Code
166830
Country
Lebanon
Facility Name
Novartis Investigative Site
City
Beirut
Country
Lebanon
Facility Name
Novartis Investigative Site
City
Sidon
ZIP/Postal Code
652
Country
Lebanon
Facility Name
VUmc, Hematology, PK2 BR012
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
Facility Name
Albert Schweitzer ziekenhuis, Hematology
City
Dordrecht
ZIP/Postal Code
3318 AT
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Oslo
ZIP/Postal Code
NO 0450
Country
Norway
Facility Name
Novartis Investigative Site
City
Lublin
ZIP/Postal Code
20 090
Country
Poland
Facility Name
Novartis Investigative Site
City
Torun
ZIP/Postal Code
87 100
Country
Poland
Facility Name
Novartis Investigative Site
City
Warszawa
ZIP/Postal Code
02 106
Country
Poland
Facility Name
Novartis Investigative Site
City
Warszawa
ZIP/Postal Code
02 776
Country
Poland
Facility Name
Novartis Investigative Site
City
Wroclaw
ZIP/Postal Code
50 367
Country
Poland
Facility Name
Novartis Investigative Site
City
Braga
ZIP/Postal Code
4710243
Country
Portugal
Facility Name
Novartis Investigative Site
City
Porto
ZIP/Postal Code
4200-072
Country
Portugal
Facility Name
Novartis Investigative Site
City
Saint Petersburg
ZIP/Postal Code
191024
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Saratov
ZIP/Postal Code
410012
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Malaga
State/Province
Andalucia
ZIP/Postal Code
29010
Country
Spain
Facility Name
Novartis Investigative Site
City
Salamanca
State/Province
Castilla Y Leon
ZIP/Postal Code
37007
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08036
Country
Spain
Facility Name
Novartis Investigative Site
City
L'Hospitalet De Llobregat
State/Province
Catalunya
ZIP/Postal Code
08907
Country
Spain
Facility Name
Novartis Investigative Site
City
La Laguna
State/Province
Santa Cruz De Tenerife
ZIP/Postal Code
38320
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28006
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Novartis Investigative Site
City
Zaragoza
ZIP/Postal Code
50009
Country
Spain
Facility Name
Novartis Investigative Site
City
Lulea
ZIP/Postal Code
SE 971 80
Country
Sweden
Facility Name
Novartis Investigative Site
City
Lund
ZIP/Postal Code
SE-221 85
Country
Sweden
Facility Name
Novartis Investigative Site
City
Uppsala
ZIP/Postal Code
SE-751 85
Country
Sweden
Facility Name
Novartis Investigative Site
City
Mueang Nonthaburi
State/Province
Muang
ZIP/Postal Code
40002
Country
Thailand
Facility Name
Novartis Investigative Site
City
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Facility Name
Novartis Investigative Site
City
Chiang Mai
ZIP/Postal Code
50200
Country
Thailand
Facility Name
Novartis Investigative Site
City
Ankara
ZIP/Postal Code
06100
Country
Turkey
Facility Name
Novartis Investigative Site
City
Istanbul
ZIP/Postal Code
34899
Country
Turkey
Facility Name
Novartis Investigative Site
City
Izmir
ZIP/Postal Code
35340
Country
Turkey

12. IPD Sharing Statement

Citations:
PubMed Identifier
33301738
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.
Results Reference
derived

Learn more about this trial

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

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